Vaccines

Research

18 pages, 2232 KiB

Open AccessArticle

Production and Immunogenicity of a Tag-Free Recombinant Chimera Based on PfMSP-1 and PfMSP-3 Using Alhydrogel and Dipeptide-Based Hydrogels

by Gaurav Anand, Saikat Biswas, Nitin Yadav, Paushali Mukherjee and Virander Singh Chauhan

Vaccines 2021, 9(7), 782; https://doi.org/10.3390/vaccines9070782 - 13 Jul 2021

Cited by 7 | Viewed by 3263

Abstract

A fusion chimeric vaccine comprising multiple protective domains of different blood-stage Plasmodium falciparum antigens is perhaps necessary for widening the protective immune responses and reducing the morbidity caused by the disease. Here we continue to build upon the prior work of developing a [...] Read more.

A fusion chimeric vaccine comprising multiple protective domains of different blood-stage Plasmodium falciparum antigens is perhaps necessary for widening the protective immune responses and reducing the morbidity caused by the disease. Here we continue to build upon the prior work of developing a recombinant fusion chimera protein, His-tagged PfMSP-Fu24, by producing it as a tag-free recombinant protein. In this study, tag-free recombinant PfMSPFu24 (rFu24) was expressed in Escherichia coli, and the soluble protein was purified using a three-step purification involving ammonium sulphate precipitation followed by 2-step ion exchange chromatography procedures and shown that it was highly immunogenic with the human-compatible adjuvant Alhydrogel. We further investigated two dipeptides, phenylalanine-α, β-dehydrophenylalanine (FΔF) and Leucine-α, β-dehydrophenylalanine (LΔF) based hydrogels as effective delivery platforms for rFu24. These dipeptides self-assembled spontaneously to form a highly stable hydrogel under physiological conditions. rFu24 was efficiently entrapped in both the F∆F and L∆F hydrogels, and the three-dimensional (3D) mesh-like structures of the hydrogels remained intact after the entrapment of the antigen. The two hydrogels significantly stimulated rFu24-specific antibody titers, and the sera from the immunized mice showed an invasion inhibitory activity comparable to that of Alhydrogel. Easily synthesized dipeptide hydrogels can be used as an effective antigen delivery platform to induce immune responses. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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18 pages, 1705 KiB

Open AccessArticle

Thermostable, Dissolvable Buccal Film Rotavirus Vaccine Is Highly Effective in Neonatal Gnotobiotic Pig Challenge Model

by Casey Hensley, Peng Zhou, Sofia Schnur, Hassan M. Mahsoub, Yu Liang, Min-Xuan Wang, Caroline Page, Lijuan Yuan and Victor Bronshtein

Vaccines 2021, 9(5), 437; https://doi.org/10.3390/vaccines9050437 - 30 Apr 2021

Cited by 8 | Viewed by 2863

Abstract

Difficulties related to storage and transport of currently available live oral rotavirus vaccines can have detrimental consequences on the efficacy of the vaccines. Thus, there is a great need for thermostable vaccines that can eliminate the necessity for cold chain storage or reconstitution [...] Read more.

Difficulties related to storage and transport of currently available live oral rotavirus vaccines can have detrimental consequences on the efficacy of the vaccines. Thus, there is a great need for thermostable vaccines that can eliminate the necessity for cold chain storage or reconstitution before administration. In this study, we developed a dissolvable oral polymeric film comprised of a live attenuated thermostable tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) powder and antacid (CaCO₃). Immunogenicity and protective efficacy of the vaccine after buccal delivery was evaluated in the gnotobiotic pig model of human rotavirus (HRV) infection and diarrhea. Two doses of the vaccine were highly immunogenic and conferred strong protection against virus shedding and diarrhea upon challenge with a high dose of a virulent G1 HRV in gnotobiotic pigs. Those pigs vaccinated with the preserved film vaccine had significantly delayed onset of diarrhea; reduced duration and area under the curve of diarrhea; delayed onset of fecal virus shedding; and reduced duration and peak of fecal virus shedding titers compared to pigs in both the placebo and the reconstituted liquid oral RRV-TV vaccine groups. Associated with the strong protection, high titers of serum virus neutralization antibodies against each of the four RRV-TV mono-reassortants and G1 HRV-specific serum IgA and IgG antibodies, as well as intestinal IgA antibodies, were induced by the preserved film vaccine. These results demonstrated the effectiveness of our thermostable buccal film rotavirus vaccine and warrant further investigation into the promise of the novel technology in addressing drawbacks of the current live oral HRV vaccines. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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22 pages, 2538 KiB

Open AccessArticle

Vaccine Efficacy of a Newly Developed Feed-Based Whole-Cell Polyvalent Vaccine against Vibriosis, Streptococcosis and Motile Aeromonad Septicemia in Asian Seabass, Lates calcarifer

by Aslah Mohamad, Mohd Zamri-Saad, Mohammad Noor Azmai Amal, Nurhidayu Al-saari, Md. Shirajum Monir, Yong Kit Chin and Ina-Salwany Md Yasin

Vaccines 2021, 9(4), 368; https://doi.org/10.3390/vaccines9040368 - 10 Apr 2021

Cited by 35 | Viewed by 5790

Abstract

Multiple infections of several bacterial species are often observed under natural farm conditions. The infections would cause a much more significant loss compared to a single infectious agent. Vaccination is an essential strategy to prevent diseases in aquaculture, and oral vaccination has been [...] Read more.

Multiple infections of several bacterial species are often observed under natural farm conditions. The infections would cause a much more significant loss compared to a single infectious agent. Vaccination is an essential strategy to prevent diseases in aquaculture, and oral vaccination has been proposed as a promising technique since it requires no handling of the fish and is easy to perform. This research attempts to develop and evaluate a potential feed-based polyvalent vaccine that can be used to treat multiple infections by Vibrios spp., Streptococcus agalactiae, and Aeromonas hydrophila, simultaneously. The oral polyvalent vaccine was prepared by mixing formalin-killed vaccine of V. harveyi, S. agalactiae, and A. hydrophila strains with commercial feed pellet, and palm oil as an adjuvant was added to improve their antigenicity. Thereafter, a vaccinated feed pellet was tested for feed quality analysis in terms of feed stability in water, proximate nutrient analysis, and palatability, safety, and growth performance using Asian seabass, Lates calcarifer as a fish host model. For immune response analysis, a total of 300 Asian seabass juveniles (15.8 ± 2.6 g) were divided into two groups in triplicate. Fish of group 1 were not vaccinated, while group 2 was vaccinated with the feed-based polyvalent vaccine. Vaccinations were carried out on days 0 and 14 with oral administration of the feed containing the bacterin at 5% body weight. Samples of serum for antibody and lysozyme study and the spleen and gut for gene expression analysis were collected at 7-day intervals for 6 weeks. Its efficacy in protecting fish was evaluated in aquarium challenge. Following vaccination by the polyvalent feed-based vaccine, IgM antibody levels showed a significant (p < 0.05) increase in serum against Vibrio harveyi, Aeromonas hydrophila, and Streptococcus agalactiae and reached the peak at week 3, 5, and 6, respectively. The high-stimulated antibody in the serum remained significantly higher than the control (p < 0.05) at the end of the 6 weeks vaccination trial. Not only that, but the serum lysozyme level was also increased significantly at week 4 (p < 0.05) as compared to the control treatment. The immune-related gene, dendritic cells, C3, Chemokine ligand 4 (CCL4), and major histocompatibility complex class I (MHC I) showed significantly higher expression (p < 0.05) after the fish were vaccinated with the oral vaccine. In the aquarium challenge, the vaccine provided a relative percentage survival of 75 ± 7.1%, 80 ± 0.0%, and 80 ± 0.0% after challenge with V. harveyi, A. hydrophila, and S. agalactiae, respectively. Combining our results demonstrate that the feed-based polyvalent vaccine could elicit significant innate and adaptive immunological responses, and this offers an opportunity for a comprehensive immunization against vibriosis, streptococcosis, and motile aeromonad septicemia in Asian seabass, Lates calcarifer. Nevertheless, this newly developed feed-based polyvalent vaccination can be a promising technique for effective and large-scale fish immunization in the aquaculture industry shortly. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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14 pages, 1725 KiB

Open AccessArticle

Short or Long Interval between Priming and Boosting: Does It Impact on the Vaccine Immunogenicity?

by Elena Pettini, Gabiria Pastore, Fabio Fiorino, Donata Medaglini and Annalisa Ciabattini

Vaccines 2021, 9(3), 289; https://doi.org/10.3390/vaccines9030289 - 20 Mar 2021

Cited by 18 | Viewed by 5560

Abstract

Characterizing the impact of the vaccination schedule on the induction of B and T cell immune responses is critical for improving vaccine immunogenicity. Here we compare the effect of a short (4 weeks) or a long (18 weeks) interval between priming and boosting [...] Read more.

Characterizing the impact of the vaccination schedule on the induction of B and T cell immune responses is critical for improving vaccine immunogenicity. Here we compare the effect of a short (4 weeks) or a long (18 weeks) interval between priming and boosting in mice, using a model vaccine formulation based on the chimeric tuberculosis vaccine antigen H56 combined with alum. While no significant difference was observed in serum antigen-specific IgG response and the induction of antigen-specific T follicular helper cells into draining lymph nodes after the two immunization schedules, a longer interval between priming and boosting elicited a higher number of germinal center-B cells and H56-specific antibody-secreting cells and modulated the effector function of reactivated CD4+ T cells. These data show that the scheduling of the booster immunization could affect the immune response elicited by vaccination modulating and improving the immunogenicity of the vaccine. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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11 pages, 1134 KiB

Open AccessCommunication

Immunogenicity of Calvenza-03 EIV/EHV^® Vaccine in Horses: Comparative In Vivo Study

by Selvaraj Pavulraj, Tobias Bergmann, Claudia Maria Trombetta, Serena Marchi, Emanuele Montomoli, Sidi Sefiane El Alami, Roberto Ragni-Alunni, Nikolaus Osterrieder and Walid Azab

Vaccines 2021, 9(2), 166; https://doi.org/10.3390/vaccines9020166 - 17 Feb 2021

Cited by 7 | Viewed by 3236

Abstract

Equine influenza (EI) is a highly contagious acute respiratory disease of equines that is caused mainly by the H3N8 subtype of influenza A virus. Vaccinating horses against EI is the most effective strategy to prevent the infection. The current study aimed to compare [...] Read more.

Equine influenza (EI) is a highly contagious acute respiratory disease of equines that is caused mainly by the H3N8 subtype of influenza A virus. Vaccinating horses against EI is the most effective strategy to prevent the infection. The current study aimed to compare the kinetics of EI-specific humoral- and cell-mediated immunity (CMI) in horses receiving either identical or mixed vaccinations. Two groups of horses were previously (six months prior) vaccinated with either Calvenza 03 EIV EHV^® (G1) or Fluvac Innovator^® (G2) vaccine. Subsequently, both groups received a booster single dose of Calvenza 03 EIV EHV^®. Immune responses were assessed after 10 weeks using single radial hemolysis (SRH), virus neutralization (VN), and EliSpot assays. Our results revealed that Calvenza-03 EIV/EHV^®-immunized horses had significantly higher protective EI-specific SRH antibodies and VN antibodies. Booster immunization with Calvenza-03 EIV/EHV^® vaccine significantly stimulated cell-mediated immune response as evidenced by significant increase in interferon-γ-secreting peripheral blood mononuclear cells. In conclusion, Calvenza-03 EIV/EHV^® vaccine can be safely and effectively used for booster immunization to elicit optimal long persisting humoral and CMI responses even if the horses were previously immunized with a heterogeneous vaccine. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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11 pages, 2049 KiB

Open AccessArticle

Vaccination with Neospora GRA6 Interrupts the Vertical Transmission and Partially Protects Dams and Offspring against Neospora caninum Infection in Mice

by Ragab M. Fereig, Hanan H. Abdelbaky and Yoshifumi Nishikawa

Vaccines 2021, 9(2), 155; https://doi.org/10.3390/vaccines9020155 - 15 Feb 2021

Cited by 1 | Viewed by 1995

Abstract

Vaccination is the mainstay of preventative measures for numerous infectious diseases. Neospora caninum infection induces storms of abortion in pregnant cows and ewes, resulting in drastic economic losses because of fetal losses and culling of the dams. Herein, we evaluated the potential of [...] Read more.

Vaccination is the mainstay of preventative measures for numerous infectious diseases. Neospora caninum infection induces storms of abortion in pregnant cows and ewes, resulting in drastic economic losses because of fetal losses and culling of the dams. Herein, we evaluated the potential of recombinant protein of N. caninum dense granule protein 6 fused with glutathione-S-transferase (NcGRA6+GST) as a vaccine candidate against neosporosis in a pregnant mouse model. The protective efficacy was investigated by subcutaneous inoculation of BALB/c mice with recombinant NcGRA6+GST (25 pmol), and GST alone (25 pmol) or phosphate-buffered saline (PBS) as the controls. This study revealed the partial ability of NcGRA6+GST to protect the dams and offspring from N. caninum infection during the critical period of pregnancy. This ability was revealed by higher survival rate and lower parasite burden in brains of offspring of the NcGRA6+GST-immunized group in comparison with the control groups. In addition, mouse dams from NcGRA6+GST-immunized groups exhibited lower clinical score and minimum alteration in body weight in comparison with PBS or GST groups after challenge with N. caninum tachyzoites. Taken together, our results suggest the efficacy of recombinant NcGRA6 for interrupting the vertical transmission of N. caninum in mice by reducing the severity of infections in dams and offspring. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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14 pages, 6644 KiB

Open AccessArticle

Immunogenicity Assessment of Different Segments and Domains of Group A Streptococcal C5a Peptidase and Their Application Potential as Carrier Protein for Glycoconjugate Vaccine Development

by Guirong Wang, Jielin Zhao, Yisheng Zhao, Subo Wang, Shaojie Feng and Guofeng Gu

Vaccines 2021, 9(2), 139; https://doi.org/10.3390/vaccines9020139 - 9 Feb 2021

Cited by 5 | Viewed by 2493

Abstract

Group A streptococcal C5a peptidase (ScpA) is a highly conserved surface virulence factor present on group A streptococcus (GAS) cell surfaces. It has attracted much more attention as a promising antigenic target for GAS vaccine development due to its high antigenicity to stimulate [...] Read more.

Group A streptococcal C5a peptidase (ScpA) is a highly conserved surface virulence factor present on group A streptococcus (GAS) cell surfaces. It has attracted much more attention as a promising antigenic target for GAS vaccine development due to its high antigenicity to stimulate specific and immunoprotective antibodies. In this study, a series of segments of ScpA were rationally designed according to the functional domains described in its crystal structure, efficiently prepared and immunologically evaluated so as to assess their potential as antigens for the development of subunit vaccines. Immunological studies revealed that Fn, Fn2, and rsScpA193 proteins were promising antigen candidates worthy for further exploration. In addition, the potential of Fn and Fn2 as carrier proteins to formulate effective glycoconjugate vaccine was also investigated. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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13 pages, 1735 KiB

Open AccessArticle

Refinement of a Live Attenuated Salmonella enterica Serovar Newport Vaccine with Improved Safety

by Shamima Nasrin, Fabien J. Fuche, Khandra T. Sears, Jennifer A. Jones, Myron M. Levine, Raphael Simon and Sharon M. Tennant

Vaccines 2021, 9(1), 57; https://doi.org/10.3390/vaccines9010057 - 16 Jan 2021

Cited by 4 | Viewed by 2957

Abstract

Non-typhoidal Salmonella (NTS) is a major cause of gastroenteritis and is responsible for approximately 93 million cases annually. In healthy individuals, gastroenteritis caused by NTS is usually self-limiting, however, NTS can cause severe invasive disease in immunocompromised patients. Very little research has been [...] Read more.

Non-typhoidal Salmonella (NTS) is a major cause of gastroenteritis and is responsible for approximately 93 million cases annually. In healthy individuals, gastroenteritis caused by NTS is usually self-limiting, however, NTS can cause severe invasive disease in immunocompromised patients. Very little research has been directed towards development of vaccines against Salmonella serogroups O:6,7 or O:8. We have constructed a live attenuated serogroup O:8 vaccine, CVD 1979, by deleting guaBA, htrA, and aroA from the genome of S. Newport. We have shown that the candidate vaccine is well tolerated in mice and elicits serum immunoglobulin G (IgG) antibodies against core O-polysaccharide (COPS) when administered orally. Immunized mice were challenged intraperitoneally with wild-type S. Newport and bacterial burden in the liver and spleen was found to be significantly reduced in the livers of immunized mice compared to control mice. We also observed moderate vaccine efficacy (45%) against lethal challenge with the serogroup O:8 serovar, S. Muenchen, but low vaccine efficacy (28%) following lethal challenge with a serogroup O:6,7 serovar, S. Virchow. In vitro, we have shown that antibodies generated by CVD 1979 only recognize lipopolysaccharide (LPS) from serogroup O:8 but not serogroup O:6,7 serovars, and that they mediate opsonophagocytic antibody (OPA) activity against serogroup O:8 but not serogroup O:6,7 serovars. We also showed that OPA activity can be blocked by pre-incubating the antisera with serogroup O:8 lipopolysaccharide. Taken together, our data demonstrate that we have constructed a well-tolerated, effective live attenuated S. Newport vaccine which elicits functional antibodies against serogroup O:8 but not O:6,7 serovars. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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15 pages, 3946 KiB

Open AccessArticle

Recombinant Baculovirus-Produced Grass Carp Reovirus Virus-Like Particles as Vaccine Candidate That Provides Protective Immunity against GCRV Genotype II Infection in Grass Carp

by Ting Gao, Caixia Gao, Siyu Wu, Yingying Wang, Jiyuan Yin, Yingying Li, Weiwei Zeng, Sven M. Bergmann and Qing Wang

Vaccines 2021, 9(1), 53; https://doi.org/10.3390/vaccines9010053 - 14 Jan 2021

Cited by 11 | Viewed by 3444

Abstract

Grass carp reovirus (GCRV) leads to severe hemorrhagic disease in grass carp (Ctenopharyngodon idella) and causes economic losses in grass carp aquaculture. Recent epidemiological investigations showed that GCRV genotype II is the dominant subtype in China. Therefore, it is very important [...] Read more.

Grass carp reovirus (GCRV) leads to severe hemorrhagic disease in grass carp (Ctenopharyngodon idella) and causes economic losses in grass carp aquaculture. Recent epidemiological investigations showed that GCRV genotype II is the dominant subtype in China. Therefore, it is very important to develop a novel vaccine for preventing diseases caused by GCRV genotype II. In this study, we employed a bac-to-bac expression system to generate GCRV-II-based virus-like particles (VLPs). Previous studies have shown that the structural proteins VP3, VP4, and VP38 encoded by the segments S3, S6, and S10 of type II GCRV are immunogenic. Hence, the GCRV-VLPs were produced by co-infection of sf9 cells with recombinant baculoviruses PFBH-VP3, PFBH-VP4, and PFBH-VP38. The expressions of VP3, VP4, and VP38 proteins in GCRV-VLPs were tested by IFA and Western blot analysis. By electron microscopic observations of ultrathin sections, purified VLPs showed that the expressed proteins are similar in shape to GCRV genotype II with a size range from 40 nm to 60 nm. The immunogenicity of GCRV-VLPs was evaluated by the injection immunization of grass carp. The analysis of serum-specific IgM antibody showed that grass carp immunized with GCRV-VLPs produced GCRV-specific antibodies. Furthermore, injection with GCRV-VLPs increased the expressions of immune-related genes (IgM, IFN, TLR3, TLR7) in the spleen and kidney. In addition, grass carp immunized with a GCRV-VLPs-based vaccine showed a relative percent survival rate (RPS) of 83.33% after challenge. The data in this study showed that GCRV-VLPs demonstrated an excellent immunogenicity and represent a promising approach for vaccine development against GCRV genotype II infection. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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17 pages, 1783 KiB

Open AccessArticle

Evaluation of the Efficacy of a Cholera Toxin-Based Staphylococcus aureus Vaccine against Bovine Intramammary Challenge

by Hussain A. Alabdullah, Elise Overgaard, Danielle Scarbrough, Janet E. Williams, Omid Mohammad Mousa, Gary Dunn, Laura Bond, Mark A. McGuire and Juliette K. Tinker

Vaccines 2021, 9(1), 6; https://doi.org/10.3390/vaccines9010006 - 24 Dec 2020

Cited by 9 | Viewed by 4159

Abstract

Staphylococcus aureus (S. aureus) is a primary agent of bovine mastitis and a source of significant economic loss for the dairy industry. We previously reported antigen-specific immune induction in the milk and serum of dairy cows following vaccination with a cholera [...] Read more.

Staphylococcus aureus (S. aureus) is a primary agent of bovine mastitis and a source of significant economic loss for the dairy industry. We previously reported antigen-specific immune induction in the milk and serum of dairy cows following vaccination with a cholera toxin A₂ and B subunit (CTA₂/B) based vaccine containing the iron-regulated surface determinant A (IsdA) and clumping factor A (ClfA) antigens of S. aureus (IsdA + ClfA-CTA₂/B). The goal of the current study was to assess the efficacy of this vaccine to protect against S. aureus infection after intramammary challenge. Six mid-lactation heifers were randomized to vaccinated and control groups. On days 1 and 14 animals were inoculated intranasally with vaccine or vehicle control, and on day 20 animals were challenged with S. aureus. Clinical outcome, milk quality, bacterial shedding, and somatic cell count (SCC) were followed for ten days post-challenge. Vaccinated animals did not show signs of clinical S. aureus mastitis and had lower SCCs compared to control animals during the challenge period. Reductions in bacterial shedding were observed but were not significant between groups. Antibody analysis of milk and serum indicated that, upon challenge, vaccinated animals produced enhanced IsdA- and ClfA-CTA₂/B specific immunoglobulin G (IgG) responses, while responses to CTA₂/B alone were not different between groups. Responses after challenge were largely IgG1 against the IsdA antigen and mixed IgG1/IgG2 against the ClfA antigen. In addition, there was a significant increase in interferon gamma (IFN-γ) expression from blood cells in vaccinated animals on day 20. While preliminary, these findings support evidence of the induction of active immunity by IsdA + ClfA-CTA₂/B, and further assessment of this vaccine is warranted. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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17 pages, 2608 KiB

Open AccessArticle

Generation and Evaluation of an African Swine Fever Virus Mutant with Deletion of the CD2v and UK Genes

by Teshale Teklue, Tao Wang, Yuzi Luo, Rongliang Hu, Yuan Sun and Hua-Ji Qiu

Vaccines 2020, 8(4), 763; https://doi.org/10.3390/vaccines8040763 - 14 Dec 2020

Cited by 66 | Viewed by 5253

Abstract

African swine fever (ASF) is a highly contagious and often lethal disease caused by African swine fever virus (ASFV). ASF emerged in China in August 2018 and has since rapidly spread into many areas of the country. The disease has caused a significant [...] Read more.

African swine fever (ASF) is a highly contagious and often lethal disease caused by African swine fever virus (ASFV). ASF emerged in China in August 2018 and has since rapidly spread into many areas of the country. The disease has caused a significant impact on China’s pig and related industries. A safe and effective vaccine is needed to prevent and control the disease. Several gene-deleted ASFVs have been reported; however, none of them is safe enough and commercially available. In this study, we report the generation of a double gene-deleted ASFV mutant, ASFV-SY18-∆CD2v/UK, from a highly virulent field strain ASFV-SY18 isolated in China. The results showed that ASFV-SY18-∆CD2v/UK lost hemadsorption properties, and the simultaneous deletion of the two genes did not significantly affect the in vitro replication of the virus in primary porcine alveolar macrophages. Furthermore, ASFV-SY18-∆CD2v/UK was attenuated in pigs. All the ASFV-SY18-∆CD2v/UK-inoculated pigs remained healthy, and none of them developed ASF-associated clinical signs. Additionally, the ASFV-SY18-∆CD2v/UK-infected pigs developed ASFV-specific antibodies, and no virus genome was detected in blood and nasal discharges at 21 and 28 days post-inoculation. More importantly, we found that all the pigs inoculated with 10⁴ TCID₅₀ of ASFV-SY18-∆CD2v/UK were protected against the challenge with the parental ASFV-SY18. However, low-level ASFV DNA was detected in blood, nasal swabs, and lymphoid tissue after the challenge. The results demonstrate that ASFV-SY18-∆CD2v/UK is safe and able to elicit protective immune response in pigs and can be a potential vaccine candidate to control ASF. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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14 pages, 2595 KiB

Open AccessArticle

Efficacy of Whole Cell Inactivated Vibrio harveyi Vaccine against Vibriosis in a Marine Red Hybrid Tilapia (Oreochromis niloticus × O. mossambicus) Model

by Nadirah Abu Nor, Mohd Zamri-Saad, Ina-Salwany Md Yasin, Annas Salleh, Farina Mustaffa-Kamal, Mohd Fuad Matori and Mohd Noor Amal Azmai

Vaccines 2020, 8(4), 734; https://doi.org/10.3390/vaccines8040734 - 4 Dec 2020

Cited by 21 | Viewed by 3617

Abstract

Vibrio harveyi causes vibriosis in various commercial marine fish species. The infection leads to significant economic losses for aquaculture farms, and vaccination is an alternative approach for the prevention and control of fish diseases for aquaculture sustainability. This study describes the use of [...] Read more.

Vibrio harveyi causes vibriosis in various commercial marine fish species. The infection leads to significant economic losses for aquaculture farms, and vaccination is an alternative approach for the prevention and control of fish diseases for aquaculture sustainability. This study describes the use of formalin-killed Vibrio harveyi (FKVh) strain Vh1 as a vaccine candidate to stimulate innate and adaptive immunities against vibriosis in a marine red hybrid tilapia model. Tilapia are fast growing; cheap; resistant to diseases; and tolerant to adverse environmental conditions of fresh water, brackish water, and marine water and because of these advantages, marine red hybrid tilapia is a suitable candidate as a model to study fish diseases and vaccinations against vibriosis. A total of 180 healthy red hybrid tilapias were gradually adapted to the marine environment before being divided into two groups, with 90 fish in each group and were kept in triplicate with 30 fish per tank. Group 1 was vaccinated intraperitoneally with 100 µL of FKVh on week 0, and a booster dose was similarly administered on week 2. Group 2 was similarly injected with PBS. Skin mucus, serum, and gut lavage were collected weekly for enzyme-linked immunosorbent assay (ELISA) and a lysozyme activity assay from a total of 30 fish of each group. On week 4, the remaining 60 fish of Groups 1 and 2 were challenged with 10⁸ cfu/fish of live Vibrio harveyi. The clinical signs were monitored while the survival rate was recorded for 48 h post-challenge. Vaccination with FKVh resulted in a significantly (p < 0.05) higher rate of survival (87%) compared to the control (20%). The IgM antibody titer and lysozyme activities of Group 1 were significantly (p < 0.05) higher than the unvaccinated Groups 2 in most weeks throughout the experiment. Therefore, the intraperitoneal exposure of marine red hybrid tilapia to killed V. harveyi enhanced the resistance and antibody response of the fish against vibriosis. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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13 pages, 1769 KiB

Open AccessArticle

The Immunogenic and Immunoprotective Activities of Recombinant Chimeric T. gondii Proteins Containing AMA1 Antigen Fragments

by Justyna Gatkowska, Katarzyna Dzitko, Bartłomiej Tomasz Ferra, Lucyna Holec-Gąsior, Malwina Kawka and Bożena Dziadek

Vaccines 2020, 8(4), 724; https://doi.org/10.3390/vaccines8040724 - 2 Dec 2020

Cited by 5 | Viewed by 2376

Abstract

Toxoplasmosis, one of the most common parasitoses worldwide, is potentially dangerous for individuals with a weakened immune system, but specific immunoprophylaxis intended for humans is still lacking. Thus, efforts have been made to create an efficient universal vaccine for both animals and humans [...] Read more.

Toxoplasmosis, one of the most common parasitoses worldwide, is potentially dangerous for individuals with a weakened immune system, but specific immunoprophylaxis intended for humans is still lacking. Thus, efforts have been made to create an efficient universal vaccine for both animals and humans to overcome the shortcomings of currently used treatment methods and protect all hosts against toxoplasmosis. The current work represents a relatively new approach to vaccine development based on recombinant chimeric Toxoplasma gondii antigens. In the present research, three tetravalent chimeric proteins containing different portions of the parasite’s AMA1 antigen—AMA1^domain^I-SAG2-GRA1-ROP1_L (A^NSGR), AMA1^domains^II,^III-SAG2-GRA1-ROP1_L (A^CSGR) and AMA1^full^protein-SAG2-GRA1-ROP1_L (A^FSGR)—were tested for their immunogenic and immunoprotective capacities. All tested proteins were immunogenic, as evidenced by the triggering of specific humoral and cellular immune responses in vaccinated C3H/HeOuJ mice, defined by the production of specific IgG (IgG1/IgG2a) antibodies in vivo and synthesis of key Th1/Th2 cytokines by Toxoplasma lysate antigen-stimulated splenocytes in vitro. Although all tested preparations provided partial protection against chronic toxoplasmosis in immunized and T. gondii-challenged mice, the intensity of the generated immunoprotection depended on the fragment of the AMA1 antigen incorporated into the chimeric antigen’s structure. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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11 pages, 1361 KiB

Open AccessArticle

Redefining Non-Inferiority in Anamnestic Antibody Responses Using the Mean Increase of Log-Transformed Antibody Titers after Revaccination: Secondary Analysis of a Randomized Controlled Rabies Vaccination Trial

by Lisanne A. Overduin, Patrick H. P. Soentjens, Jelle J. Goeman, Magdalena A. Berkowska, Jacques J. M. van Dongen and Leo G. Visser

Vaccines 2020, 8(4), 721; https://doi.org/10.3390/vaccines8040721 - 2 Dec 2020

Cited by 2 | Viewed by 2532

Abstract

Non-inferiority in the anamnestic antibody response is conventionally determined by comparing seroconversion rates after revaccination. However, this approach is inadequate in the case of high pre-booster antibody titers. Therefore, we propose an alternative method to determine non-inferiority of booster responses. We used anonymized [...] Read more.

Non-inferiority in the anamnestic antibody response is conventionally determined by comparing seroconversion rates after revaccination. However, this approach is inadequate in the case of high pre-booster antibody titers. Therefore, we propose an alternative method to determine non-inferiority of booster responses. We used anonymized data from a randomized controlled trial (NCT01388985; EudraCT 2011-001612-62) in 500 adults, comparing a two-visit primary vaccination schedule (two intradermal 0.1 mL rabies vaccine doses on day 0 and 7) with a three-visit schedule (single intradermal 0.1 mL dose on day 0, 7, and 28). Participants were revaccinated intradermally (single dose) 1 to 3 years later. Rabies virus neutralizing antibody titers were measured on day 0 and 7 after revaccination. After log₃-transformation of antibody titers, the mean increase in titers after revaccination was compared between schedules. Non-inferiority was defined as the lower bound of the two-sided 95% confidence interval not exceeding −0.369. Four hundred and ten participants fulfilled the inclusion criteria. The mean increase in log₃ titer was 2.21 and 2.31 for the two-visit and three-visit schedule, respectively. The difference between these increases was −0.10 [−0.28, 0.08], meeting the non-inferiority criterion. In conclusion, comparing mean increases in log-transformed titers after revaccination appears to be a feasible and more informative method of studying non-inferiority regarding the anamnestic antibody response. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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15 pages, 2989 KiB

Open AccessArticle

Recombinant Live Attenuated Influenza Virus Expressing Conserved G-Protein Domain in a Chimeric Hemagglutinin Molecule Induces G-Specific Antibodies and Confers Protection against Respiratory Syncytial Virus

by Yu-Jin Jung, Yu-Na Lee, Ki-Hye Kim, Youri Lee, Subbiah Jeeva, Bo Ryoung Park and Sang-Moo Kang

Vaccines 2020, 8(4), 716; https://doi.org/10.3390/vaccines8040716 - 1 Dec 2020

Cited by 7 | Viewed by 3339

Abstract

Respiratory syncytial virus (RSV) is one of the most important pathogens causing significant morbidity and mortality in infants and the elderly. Live attenuated influenza vaccine (LAIV) is a licensed vaccine platform in humans and it is known to induce broader immune responses. RSV [...] Read more.

Respiratory syncytial virus (RSV) is one of the most important pathogens causing significant morbidity and mortality in infants and the elderly. Live attenuated influenza vaccine (LAIV) is a licensed vaccine platform in humans and it is known to induce broader immune responses. RSV G attachment proteins mediate virus binding to the target cells and they contain a conserved central domain with neutralizing epitopes. Here, we generated recombinant LAIV based on the attenuated A/Puerto Rico/8/1934 virus backbone, expressing an RSV conserved G-domain in a chimeric hemagglutinin (HA) fusion molecule (HA-G). The attenuated phenotypes of chimeric HA-G LAIV were evident by restricted replication in the upper respiratory tract and low temperature growth characteristics. The immunization of mice with chimeric HA-G LAIV induced significant increases in G-protein specific IgG2a (T helper type 1) and IgG antibody-secreting cell responses in lung, bronchioalveolar fluid, bone marrow, and spleens after RSV challenge. Vaccine-enhanced disease that is typically caused by inactivated-RSV vaccination was not observed in chimeric HA-G LAIV as analyzed by lung histopathology. These results in this study suggest a new approach of developing an RSV vaccine candidate while using recombinant LAIV, potentially conferring protection against influenza virus and RSV. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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15 pages, 3616 KiB

Open AccessArticle

Antibody Responses to SARS-CoV-2 Antigens in Humans and Animals

by Hyunsuh Kim, Patrick Seiler, Jeremy C. Jones, Granger Ridout, Kristi P. Camp, Thomas P. Fabrizio, Trushar Jeevan, Lance A. Miller, Robert E. Throm, Francesca Ferrara, Richard L. Fredrickson, James F. Lowe, Leyi Wang, Solomon O. Odemuyiwa, Xiu-Feng Wan and Richard J. Webby

Vaccines 2020, 8(4), 684; https://doi.org/10.3390/vaccines8040684 - 16 Nov 2020

Cited by 10 | Viewed by 4953

Abstract

To optimize the public health response to coronavirus disease 2019 (COVID-19), we must first understand the antibody response to individual proteins on the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the antibody’s cross reactivity to other coronaviruses. Using a panel of 37 [...] Read more.

To optimize the public health response to coronavirus disease 2019 (COVID-19), we must first understand the antibody response to individual proteins on the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and the antibody’s cross reactivity to other coronaviruses. Using a panel of 37 convalescent COVID-19 human serum samples, we showed that the magnitude and specificity of responses varied across individuals, independent of their reactivity to seasonal human coronaviruses (HCoVs). These data suggest that COVID-19 vaccines will elicit primary humoral immune responses in naïve individuals and variable responses in those previously exposed to SARS-CoV-2. Unlike the limited cross-coronavirus reactivities in humans, serum samples from 96 dogs and 10 cats showed SARS-CoV-2 protein-specific responses focused on non–S1 proteins. The correlation of this response with those to other coronaviruses suggests that the antibodies are cross-reactive and generated to endemic viruses within these hosts, which must be considered in seroepidemiologic studies. We conclude that substantial variation in antibody generation against coronavirus proteins will influence interpretations of serologic data in the clinical and veterinary settings. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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16 pages, 1573 KiB

Open AccessArticle

Macrophage Activation Assays to Evaluate the Immunostimulatory Capacity of Avibacterium paragallinarum in A Multivalent Poultry Vaccine

by Robin H. G. A. van den Biggelaar, Willem van Eden, Victor P. M. G. Rutten and Christine A. Jansen

Vaccines 2020, 8(4), 671; https://doi.org/10.3390/vaccines8040671 - 10 Nov 2020

Cited by 9 | Viewed by 3969

Abstract

High-quality vaccines are crucial to prevent infectious disease outbreaks in the poultry industry. In vivo vaccination tests are routinely used to test poultry vaccines for their potency, i.e., their capacity to induce protection against the targeted diseases. A better understanding of how poultry [...] Read more.

High-quality vaccines are crucial to prevent infectious disease outbreaks in the poultry industry. In vivo vaccination tests are routinely used to test poultry vaccines for their potency, i.e., their capacity to induce protection against the targeted diseases. A better understanding of how poultry vaccines activate immune cells will facilitate the replacement of in vivo potency tests for in vitro assays. Using the chicken macrophage-like HD11 cell line as a model to evaluate innate immune responses, the current explorative study addresses the immunostimulatory capacity of an inactivated multivalent vaccine for infectious bronchitis, Newcastle disease, egg-drop syndrome, and infectious coryza. The vaccine stimulated HD11 cells to produce nitric oxide and to express pro-inflammatory cytokines IL-1β, TNF, and IL-12p40, chemokines CXCLi1 and CXCLi2, and the anti-inflammatory cytokine IL-10, but only when inactivated Avibacterium paragallinarum, the causative agent of infectious coryza, was present. Lipopolysaccharides from Avibacterium paragallinarum were crucial for the production of nitric oxide and expression of IL-1β and CXCLi1. The described immune parameters demonstrate the capacity of this multivalent vaccine to activate innate immune cells and may in the future, combined with antigen quantification methods, contribute to vaccine quality testing in vitro, hence the replacement of current in vivo vaccination tests. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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13 pages, 2775 KiB

Open AccessArticle

The Effects of Imprinting and Repeated Seasonal Influenza Vaccination on Adaptive Immunity after Influenza Vaccination

by Amy C. Sherman, Lilin Lai, Mary Bower, Muktha S. Natrajan, Christopher Huerta, Vinit Karmali, Jennifer Kleinhenz, Yongxian Xu, Nadine Rouphael and Mark J. Mulligan

Vaccines 2020, 8(4), 663; https://doi.org/10.3390/vaccines8040663 - 7 Nov 2020

Cited by 8 | Viewed by 2878

Abstract

(1) Background: The influenza virus continues to cause significant annual morbidity and mortality. The overall efficacy of seasonal influenza vaccination is suboptimal, which is partly due to host immune factors. The effects of imprinting and repeated seasonal influenza vaccination were investigated to assess [...] Read more.

(1) Background: The influenza virus continues to cause significant annual morbidity and mortality. The overall efficacy of seasonal influenza vaccination is suboptimal, which is partly due to host immune factors. The effects of imprinting and repeated seasonal influenza vaccination were investigated to assess for immune factors and mechanisms that impact influenza vaccine responses. (2) Methods: Twenty participants were enrolled into a prospective pilot study based on birth cohort and seasonal influenza immunization history. Immunologic parameters were assessed over a six-month period after the seasonal influenza vaccine was administered. (3) Results: There was no significant imprinting effect, as measured by hemagglutination inhibition (HAI) fold change, HAI geometric mean titer (GMT) for Day 29 or Day 180 post-vaccination and antigen- specific antibody-secreting cells (ASC) for Day 8 post-vaccination. Individuals who had minimal prior seasonal influenza vaccination had a higher magnitude ASC response and a higher HAI fold change post-vaccination than individuals who were repeatedly vaccinated. (4) Conclusions: Repeated seasonal influenza vaccination resulted in a decreased fold change of the immune response, although individuals in this cohort tended to have high HAI titers at baseline that persisted after vaccination. Imprinting effects were not observed in this cohort. These host immune factors should be considered in the development of universal influenza vaccines. ClinicalTrials.gov Identifier: NCT03686514. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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17 pages, 14085 KiB

Open AccessArticle

Safety and Immunogenicity of the GamTBvac, the Recombinant Subunit Tuberculosis Vaccine Candidate: A Phase II, Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study

by Artem P. Tkachuk, Evgeniia N. Bykonia, Liubov I. Popova, Denis A. Kleymenov, Maria A. Semashko, Vladimir P. Chulanov, Sergey B. Fitilev, Semyon L. Maksimov, Elena A. Smolyarchuk, Victor A. Manuylov, Daria V. Vasina, Vladimir A. Gushchin and Alexander L. Gintsburg

Vaccines 2020, 8(4), 652; https://doi.org/10.3390/vaccines8040652 - 3 Nov 2020

Cited by 37 | Viewed by 4543

Abstract

GamTBvac is a candidate tuberculosis vaccine with two fusion proteins, containing Ag85a, ESAT6, CFP10, and a dextran-binding domain (DBD). Phase II of a double-blind, randomized, multicenter, placebo-controlled study in parallel groups in healthy adults to evaluate the safety and immunogenicity of GamTBvac in [...] Read more.

GamTBvac is a candidate tuberculosis vaccine with two fusion proteins, containing Ag85a, ESAT6, CFP10, and a dextran-binding domain (DBD). Phase II of a double-blind, randomized, multicenter, placebo-controlled study in parallel groups in healthy adults to evaluate the safety and immunogenicity of GamTBvac in 180 previously-vaccinated with Bacillus Calmette–Guérin vaccine (BCG) healthy volunteers without Mycobacterium tuberculosis (MTB) infection was conducted. The dose (0.5 mL) of either the study drug or a placebo was administered subcutaneously twice with an 8-week interval. At eight timepoints from 14 to 150 days, whole blood and sera were assayed. Antigen-specific T-cell responses were measured by an in-house interferon-gamma release assay (IGRA-test), the QuantiFERON (QTF) test, and intracellular cytokine staining (ICS). For antibody response detection, the bead-based multiplex immunoassay (MIA) was applied. The vaccine confirmed an acceptable safety profile previously shown in a first-in-human clinical study. After stimulation with both fusions, the highest median level of INF-γ was detected on day 21. The GamTBvac vaccine induced antigen-specific interferon-gamma release, Th1 cytokine-expressing CD4⁺ T-cells, and IgG responses and results support further clinical testing of GamTBvac. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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15 pages, 1976 KiB

Open AccessArticle

Conjugation of Human β-Defensin 2 to Spike Protein Receptor-Binding Domain Induces Antigen-Specific Protective Immunity against Middle East Respiratory Syndrome Coronavirus Infection in Human Dipeptidyl Peptidase 4 Transgenic Mice

by Ju Kim, Ye Lin Yang, Yongsu Jeong and Yong-Suk Jang

Vaccines 2020, 8(4), 635; https://doi.org/10.3390/vaccines8040635 - 1 Nov 2020

Cited by 14 | Viewed by 3276

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory symptoms. Due to the lack of medical countermeasures, effective and safe vaccines against MERS-CoV infection are urgently required. Although different types of candidate vaccines have been developed, their immunogenicity is limited, and the [...] Read more.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory symptoms. Due to the lack of medical countermeasures, effective and safe vaccines against MERS-CoV infection are urgently required. Although different types of candidate vaccines have been developed, their immunogenicity is limited, and the dose and administration route need optimization to achieve optimal protection. We here investigated the potential use of human β-defensin 2 (HBD 2) as an adjuvant to enhance the protection provided by MERS-CoV vaccination. We found that immunization of human dipeptidyl peptidase 4 (hDPP4)-transgenic (hDPP4-Tg) mice with spike protein receptor-binding domain (S RBD) conjugated with HBD 2 (S RBD-HBD 2) induced potent antigen (Ag)-specific adaptive immune responses and protected against MERS-CoV infection. In addition, immunization with S RBD-HBD 2 alleviated progressive pulmonary fibrosis in the lungs of MERS-CoV-infected hDPP4-Tg mice and suppressed endoplasmic reticulum stress signaling activation upon viral infection. Compared to intramuscular administration, intranasal administration of S RBD-HBD 2 induced more potent mucosal IgA responses and was more effective for protecting against intranasal MERS-CoV infection. In conclusion, our findings suggest that HBD 2 potentiates Ag-specific immune responses against viral Ag and can be used as an adjuvant enhancing the immunogenicity of subunit vaccine candidates against MERS-CoV. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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20 pages, 2651 KiB

Open AccessArticle

Flexible RSV Prefusogenic Fusion Glycoprotein Exposes Multiple Neutralizing Epitopes that May Collectively Contribute to Protective Immunity

by Nita Patel, Jing-Hui Tian, Rhonda Flores, Kelsey Jacobson, Michelle Walker, Alyse Portnoff, Mimi Gueber-Xabier, Michael J. Massare, Greg Glenn, Larry Ellingsworth and Gale Smith

Vaccines 2020, 8(4), 607; https://doi.org/10.3390/vaccines8040607 - 14 Oct 2020

Cited by 12 | Viewed by 5640

Abstract

Human respiratory syncytial virus (RSV) is a cause of lower respiratory tract infection in infants, young children, and older adults. There is no licensed vaccine and prophylactic treatment options are limited. The RSV fusion (F) glycoprotein is a target of host immunity and [...] Read more.

Human respiratory syncytial virus (RSV) is a cause of lower respiratory tract infection in infants, young children, and older adults. There is no licensed vaccine and prophylactic treatment options are limited. The RSV fusion (F) glycoprotein is a target of host immunity and thus a focus for vaccine development. F-trimers are metastable and undergo significant rearrangements from the prefusion to a stable postfusion structure with neutralizing epitopes on intermediate structures. We hypothesize that vaccine strategies that recapitulate the breathable F quaternary structure, and provide accessibility of B-cells to epitopes on intermediate conformations, may collectively contribute to protective immunity, while rigid prefusion F structures restrict access to key protective epitopes. To test this hypothesis, we used the near full-length prefusogenic F as a backbone to construct three prefusion F variants with substitutions in the hydrophobic head cavity: (1) disulfide bond mutant (DS), (2) space filling hydrophobic amino acid substitutions (Cav1), and (3) DS, Cav1 double mutant (DS-Cav1). In this study, we compared the immunogenicity of prefusogenic F to prefusion F variants in two animal models. Native prefusogenic F was significantly more immunogenic, producing high titer antibodies to prefusogenic, prefusion, and postfusion F structures, while animals immunized with DS or DS-Cav1 produced antibodies to prefusion F. Importantly, prefusogenic F elicited antibodies that target neutralizing epitopes including prefusion-specific site zero (Ø) and V and conformation-independent neutralizing sites II and IV. Immunization with DS or DS-Cav1 elicited antibodies primarily to prefusion-specific sites Ø and V with little or no antibodies to other key neutralizing sites. Animals immunized with prefusogenic F also had significantly higher levels of antibodies that cross-neutralized RSV A and B subtypes, while immunization with DS or DS-Cav1 produced antibodies primarily to the A subtype. We conclude that breathable trimeric vaccines that closely mimic the native F-structure, and incorporate strategies for B-cell accessibility to protective epitopes, are important considerations for vaccine design. F structures locked in a single conformation restrict access to neutralizing epitopes that may collectively contribute to destabilizing F-trimers important for broad protection. These results also have implications for vaccine strategies targeting other type 1 integral membrane proteins. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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14 pages, 974 KiB

Open AccessArticle

Humoral Immune Response of Thai Dogs after Oral Vaccination against Rabies with the SPBN GASGAS Vaccine Strain

by Kansuda Leelahapongsathon, Suwicha Kasemsuwan, Tanu Pinyopummintr, Orawan Boodde, Parinya Phawaphutayanchai, Nirut Aiyara, Katharina Bobe, Ad Vos, Virginia Friedrichs, Thomas Müller, Conrad M. Freuling and Karoon Chanachai

Vaccines 2020, 8(4), 573; https://doi.org/10.3390/vaccines8040573 - 1 Oct 2020

Cited by 22 | Viewed by 3712

Abstract

Applied research is crucial in pushing the boundaries and finding a solution to the age-old problem of dog-mediated rabies. Although oral vaccination of dogs is considered to have great potential in mass dog vaccination campaigns and could have far-reaching benefits, it is perhaps [...] Read more.

Applied research is crucial in pushing the boundaries and finding a solution to the age-old problem of dog-mediated rabies. Although oral vaccination of dogs is considered to have great potential in mass dog vaccination campaigns and could have far-reaching benefits, it is perhaps the most ignored of all available tools in efforts to eliminate dog-mediated rabies, not least because of limited data on immunogenicity, efficacy, and safety of potential oral rabies vaccine candidates. In this study, the long-term immunogenicity in local Thai dogs after oral administration of the highly attenuated 3rd generation rabies virus vaccine strain SPBN GASGAS was assessed. The oral rabies vaccine was administered to dogs by either direct oral administration (n = 10) or by offering a vaccine loaded intestine bait (n = 15). The humoral immune response was then compared to three groups of dogs; a group that received a parenteral delivered inactivated rabies vaccine (n = 10), a group offered a placebo intestine bait (n = 7), and a control group (n = 4) for an observation period of 365 days. There was no significant difference in the immune response of dogs that received oral and parenteral vaccine in terms of magnitude, kinetics, and persistence of both rabies virus (RABV) neutralizing (RFFIT) and binding (ELISA) antibodies. Although the single parenteral injection of an inactivated rabies vaccine mounted a slightly higher humoral immune response than the orally delivered live vaccine, RABV specific antibodies of both types were still detectable after one year in most animals for all treatment groups and resulted in no difference in seropositivity. Characterization of rabies specific antibodies revealed two main classes of antibodies involved in the immune response of dogs vaccinated. While IgM antibodies were the first to appear, the succeeding IgG response was mainly IgG2 dominated independent of the vaccine type used. The results support the view that SPBN GASGAS induces a sustained detectable immune response in local dogs both after direct oral administration and via bait application. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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16 pages, 3111 KiB

Open AccessArticle

Association of Porcine Swine Leukocyte Antigen (SLA) Haplotypes with B- and T-Cell Immune Response to Foot-and-Mouth Disease Virus (FMDV) Peptides

by Patricia de León, Rodrigo Cañas-Arranz, Yago Saez, Mar Forner, Sira Defaus, Dolores Cuadra, María J. Bustos, Elisa Torres, David Andreu, Esther Blanco, Francisco Sobrino and Sabine E. Hammer

Vaccines 2020, 8(3), 513; https://doi.org/10.3390/vaccines8030513 - 8 Sep 2020

Cited by 8 | Viewed by 3520

Abstract

Dendrimer peptides are promising vaccine candidates against the foot-and-mouth disease virus (FMDV). Several B-cell epitope (B₂T) dendrimers, harboring a major FMDV antigenic B-cell site in VP1 protein, are covalently linked to heterotypic T-cell epitopes from 3A and/or 3D proteins, and elicited [...] Read more.

Dendrimer peptides are promising vaccine candidates against the foot-and-mouth disease virus (FMDV). Several B-cell epitope (B₂T) dendrimers, harboring a major FMDV antigenic B-cell site in VP1 protein, are covalently linked to heterotypic T-cell epitopes from 3A and/or 3D proteins, and elicited consistent levels of neutralizing antibodies and IFN-γ-producing cells in pigs. To address the contribution of the highly polymorphic nature of the porcine MHC (SLA, swine leukocyte antigen) on the immunogenicity of B₂T dendrimers, low-resolution (Lr) haplotyping was performed. We looked for possible correlations between particular Lr haplotypes with neutralizing antibody and T-cell responses induced by B₂T peptides. In this study, 63 pigs immunized with B₂T dendrimers and 10 non-immunized (control) animals are analyzed. The results reveal a robust significant correlation between SLA class-II Lr haplotypes and the T-cell response. Similar correlations of T-cell response with SLA class-I Lr haplotypes, and between B-cell antibody response and SLA class-I and SLA class-II Lr haplotypes, were only found when the sample was reduced to animals with Lr haplotypes represented more than once. These results support the contribution of SLA class-II restricted T-cells to the magnitude of the T-cell response and to the antibody response evoked by the B₂T dendrimers, being of potential value for peptide vaccine design against FMDV. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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17 pages, 3469 KiB

Open AccessArticle

LvYY1 Activates WSSV ie1 Promoter for Enhanced Vaccine Production and Efficacy

by Li-Na Tao, Ze-Hui Liu, Hui-Ling Xu, Ying Lu, Min Liao and Fang He

Vaccines 2020, 8(3), 510; https://doi.org/10.3390/vaccines8030510 - 8 Sep 2020

Cited by 3 | Viewed by 3050

Abstract

The baculovirus expression vector system (BEVS) has been used as a preferred platform for the production of recombinant protein complexes and efficacious vaccines. However, limited protein yield hinders the application of BEVS. It is well accepted that transcription enhancers are capable of increasing [...] Read more.

The baculovirus expression vector system (BEVS) has been used as a preferred platform for the production of recombinant protein complexes and efficacious vaccines. However, limited protein yield hinders the application of BEVS. It is well accepted that transcription enhancers are capable of increasing translational efficiency of mRNAs, thereby achieving better protein production. In this study, the ability of LvYY1 as a transcription enhancer was assessed. LvYY1 could interact with the WSSV ie1 promoter via binding to special DNA sites in BEVS. The effects of LvYY1 on protein expression mediated by WSSV ie1 promoter of BEVS was investigated using eGFP as a reporter gene. Enhanced eGFP expression was observed in Sf-9 cells with LvYY1. On this basis, a modified vector combining ie1 promoter and LvYY1 was developed to express either secreting CSFV E2 or baculovirus surface displayed H5 HA of AIVs. Compared to control groups without LvYY1, E2 protein yield increases to 1.6-fold, while H5 production improves as revealed by an upregulated hemagglutination titer of 8-fold at least. Moreover, with LvYY1, H5 displaying baculovirus driven by WSSV ie1 promoter (BV-LvYY1-ie1-HA) sustains the transduction activity in CEF cells. In chicken, BV-LvYY1-ie1-HA elicits a robust immune response against H5 AIVs in the absence of adjuvant, as indicated by specific antibody and cytokine responses. The findings suggest its potential function as both a vectored and subunit vaccine. These results demonstrate that the coexpression with LvYY1 serves as a promising strategy to extensively improve the efficiency of BEVS for efficacious vaccine production. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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20 pages, 10849 KiB

Open AccessArticle

Vaccination of Mice with a Novel Trypsin from Trichinella spiralis Elicits the Immune Protection against Larval Challenge

by Yao Zhang, Jie Zeng, Yan Yan Song, Shao Rong Long, Ruo Dan Liu, Peng Jiang, Xi Zhang, Jing Cui and Zhong Quan Wang

Vaccines 2020, 8(3), 437; https://doi.org/10.3390/vaccines8030437 - 5 Aug 2020

Cited by 9 | Viewed by 3262

Abstract

Trichinella spiralis is a major foodborne parasite and has a serious threat to meat safety. Development of anti-Trichinella vaccines is prospective to eliminate Trichinella infection in food animal. The aim of this study was to assess the biological properties of a novel [...] Read more.

Trichinella spiralis is a major foodborne parasite and has a serious threat to meat safety. Development of anti-Trichinella vaccines is prospective to eliminate Trichinella infection in food animal. The aim of this study was to assess the biological properties of a novel T. spiralis trypsin (TsT) and its elicited immune protection against larval challenge. The cDNA sequence of TsT gene was cloned and expressed. Western blotting showed rTsT was identified by infection serum and anti-TsT serum. RT-PCR results revealed that TsT gene was transcribed at diverse T. spiralis lifecycle stages. The IIFT results showed that natural TsT was principally expressed at epicuticle of 5-6 day adult worms, indicating that TsT is a worm somatic antigen and adult-stage specific surface antigen. Vaccination of mice with rTsT triggered an evident humoral immune response (high levels of serum IgG, IgG1/IgG2a, and enteral sIgA), and it also induced the systemic and enteral local cellular immune response, demonstrated by an significantly elevation of cytokines IFN-γ and IL-4. The mice vaccinated with rTsT exhibited a 33.17% reduction of enteral adult worms and a 37.80% reduction of muscle larvae after larval challenge. The results showed that TsT might be considered as a candidate target antigen for anti-T. spiralis vaccines. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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12 pages, 1300 KiB

Open AccessArticle

Designing Functionally Versatile, Highly Immunogenic Peptide-Based Multiepitopic Vaccines against Foot-and-Mouth Disease Virus

by Sira Defaus, Mar Forner, Rodrigo Cañas-Arranz, Patricia de León, María J. Bustos, Miguel Rodríguez-Pulido, Esther Blanco, Francisco Sobrino and David Andreu

Vaccines 2020, 8(3), 406; https://doi.org/10.3390/vaccines8030406 - 22 Jul 2020

Cited by 8 | Viewed by 3183

Abstract

A broadly protective and biosafe vaccine against foot-and-mouth disease virus (FMDV) remains an unmet need in the animal health sector. We have previously reported solid protection against serotype O FMDV afforded by dendrimeric peptide structures harboring virus-specific B- and T-cell epitopes, and also [...] Read more.

A broadly protective and biosafe vaccine against foot-and-mouth disease virus (FMDV) remains an unmet need in the animal health sector. We have previously reported solid protection against serotype O FMDV afforded by dendrimeric peptide structures harboring virus-specific B- and T-cell epitopes, and also shown such type of multivalent presentations to be advantageous over simple B-T-epitope linear juxtaposition. Chemically, our vaccine platforms are modular constructions readily made from specified B- and T-cell epitope precursor peptides that are conjugated in solution. With the aim of developing an improved version of our formulations to be used for on-demand vaccine applications, we evaluate in this study a novel design for epitope presentation to the immune system based on a multiple antigen peptide (MAP) containing six immunologically relevant motifs arranged in dendrimeric fashion (named B₂T-TB₂). Interestingly, two B₂T units fused tail-to-tail into a single homodimer platform elicited higher B- and T-cell specific responses than former candidates, with immunization scores remaining stable even after 4 months. Moreover, this macromolecular assembly shows consistent immune response in swine, the natural FMDV host, at reduced dose. Thus, our versatile, immunogenic prototype can find application in the development of peptide-based vaccine candidates for various therapeutic uses using safer and more efficacious vaccination regimens. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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Review

Jump to: Research, Other

17 pages, 1515 KiB

Open AccessReview

Correlates of Vaccine-Induced Protection against SARS-CoV-2

by Till Koch, Sibylle C. Mellinghoff, Parichehr Shamsrizi, Marylyn M. Addo and Christine Dahlke

Vaccines 2021, 9(3), 238; https://doi.org/10.3390/vaccines9030238 - 10 Mar 2021

Cited by 43 | Viewed by 8490

Abstract

We are in the midst of a pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). SARS-CoV-2 has caused more than two million deaths after one year of the pandemic. The world is [...] Read more.

We are in the midst of a pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). SARS-CoV-2 has caused more than two million deaths after one year of the pandemic. The world is experiencing a deep economic recession. Safe and effective vaccines are needed to prevent further morbidity and mortality. Vaccine candidates against COVID-19 have been developed at an unprecedented speed, with more than 200 vaccine candidates currently under investigation. Among those, 20 candidates have entered the clinical Phase 3 to evaluate efficacy, and three have been approved by the European Medicines Agency. The aim of immunization is to act against infection, disease and/or transmission. However, the measurement of vaccine efficacy is challenging, as efficacy trials need to include large cohorts with verum and placebo cohorts. In the future, this will be even more challenging as further vaccine candidates will receive approval, an increasing number of humans will receive vaccinations and incidence might decrease. To evaluate novel and second-generation vaccine candidates, randomized placebo-controlled trials might not be appropriate anymore. Correlates of protection (CoP) could be an important tool to evaluate novel vaccine candidates, but vaccine-induced CoP have not been clearly defined for SARS-CoV-2 vaccines. In this review, we report on immunogenicity against natural SARS-CoV-2 infection, vaccine-induced immune responses and discuss immunological markers that can be linked to protection. By discussing the immunogenicity and efficacy of forerunner vaccines, we aim to give a comprehensive overview of possible efficacy measures and CoP. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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10 pages, 455 KiB

Open AccessReview

Enterovirus A71 Vaccines

by Mei-Ling Li, Shin-Ru Shih, Blanton S. Tolbert and Gary Brewer

Vaccines 2021, 9(3), 199; https://doi.org/10.3390/vaccines9030199 - 27 Feb 2021

Cited by 41 | Viewed by 5701

Abstract

Enterovirus A71 (EV-A71) is a major causative agent of hand, foot, and mouth disease (HFMD) and herpangina. Moreover, EV-A71 infection can lead to neurological complications and death. Vaccination is the most efficient way to control virus infection. There are currently three inactivated, whole [...] Read more.

Enterovirus A71 (EV-A71) is a major causative agent of hand, foot, and mouth disease (HFMD) and herpangina. Moreover, EV-A71 infection can lead to neurological complications and death. Vaccination is the most efficient way to control virus infection. There are currently three inactivated, whole EV-A71 vaccines licensed by the China NMPA (National Medical Products Administration). Several other types of vaccines, such as virus-like particles and recombinant VP1 (capsid protein), are also under development. In this review, we discuss recent advances in the development of EV-A71 vaccines. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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24 pages, 932 KiB

Open AccessReview

Multiple Levels of Immunological Memory and Their Association with Vaccination

by Zsófia Bugya, József Prechl, Tibor Szénási, Éva Nemes, Attila Bácsi and Gábor Koncz

Vaccines 2021, 9(2), 174; https://doi.org/10.3390/vaccines9020174 - 19 Feb 2021

Cited by 11 | Viewed by 6147

Abstract

Immunological memory is divided into many levels to counteract the provocations of diverse and ever-changing infections. Fast functions of effector memory and the superposition of both quantitatively and qualitatively plastic anticipatory memory responses together form the walls of protection against pathogens. Here we [...] Read more.

Immunological memory is divided into many levels to counteract the provocations of diverse and ever-changing infections. Fast functions of effector memory and the superposition of both quantitatively and qualitatively plastic anticipatory memory responses together form the walls of protection against pathogens. Here we provide an overview of the role of different B and T cell subsets and their interplay, the parallel and independent functions of the B1, marginal zone B cells, T-independent- and T-dependent B cell responses, as well as functions of central and effector memory T cells, tissue-resident and follicular helper T cells in the memory responses. Age-related limitations in the immunological memory of these cell types in neonates and the elderly are also discussed. We review how certain aspects of immunological memory and the interactions of components can affect the efficacy of vaccines, in order to link our knowledge of immunological memory with the practical application of vaccination. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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19 pages, 744 KiB

Open AccessReview

Strategies for Enhancement of Live-Attenuated Salmonella-Based Carrier Vaccine Immunogenicity

by James E. Galen, Rezwanul Wahid and Amanda D. Buskirk

Vaccines 2021, 9(2), 162; https://doi.org/10.3390/vaccines9020162 - 17 Feb 2021

Cited by 9 | Viewed by 3292

Abstract

The use of live-attenuated bacterial vaccines as carriers for the mucosal delivery of foreign antigens to stimulate the mucosal immune system was first proposed over three decades ago. This novel strategy aimed to induce immunity against at least two distinct pathogens using a [...] Read more.

The use of live-attenuated bacterial vaccines as carriers for the mucosal delivery of foreign antigens to stimulate the mucosal immune system was first proposed over three decades ago. This novel strategy aimed to induce immunity against at least two distinct pathogens using a single bivalent carrier vaccine. It was first tested using a live-attenuated Salmonella enterica serovar Typhi strain in clinical trials in 1984, with excellent humoral immune responses against the carrier strain but only modest responses elicited against the foreign antigen. Since then, clinical trials with additional Salmonella-based carrier vaccines have been conducted. As with the original trial, only modest foreign antigen-specific immunity was achieved in most cases, despite the incorporation of incremental improvements in antigen expression technologies and carrier design over the years. In this review, we will attempt to deconstruct carrier vaccine immunogenicity in humans by examining the basis of bacterial immunity in the human gastrointestinal tract and how the gut detects and responds to pathogens versus benign commensal organisms. Carrier vaccine design will then be explored to determine the feasibility of retaining as many characteristics of a pathogen as possible to elicit robust carrier and foreign antigen-specific immunity, while avoiding over-stimulation of unacceptably reactogenic inflammatory responses. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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13 pages, 1385 KiB

Open AccessReview

Immunogenicity of Alternative Dosing Schedules for HPV Vaccines among Adolescent Girls and Young Women: A Systematic Review and Meta-Analysis

by Andrew M. Secor, Matthew Driver, Brenda Kharono, Dianna Hergott, Gui Liu, Ruanne V. Barnabas, Peter Dull, Stephen E. Hawes and Paul K. Drain

Vaccines 2020, 8(4), 618; https://doi.org/10.3390/vaccines8040618 - 20 Oct 2020

Cited by 5 | Viewed by 4057

Abstract

Alternative dosing schedules for licensed human papilloma virus (HPV) vaccines, particularly single dose and extended intervals between doses (>12 months), are being considered to address vaccine shortages and improve operational flexibility. We searched PUBMED/MEDLINE for publications reporting immunogenicity data following administration of one [...] Read more.

Alternative dosing schedules for licensed human papilloma virus (HPV) vaccines, particularly single dose and extended intervals between doses (>12 months), are being considered to address vaccine shortages and improve operational flexibility. We searched PUBMED/MEDLINE for publications reporting immunogenicity data following administration of one of the licensed HPV vaccines (2vHPV, 4vHPV, and 9vHPV) to females aged 9–26 years. We conducted non-inferiority analyses comparing alternative to standard schedules using mixed effects meta-regression controlling for baseline HPV status and disaggregated by vaccine, subtype, time point, and age group (9–14 and 15–26 years). Non-inferiority was defined as the lower bound of the 95% confidence interval (CI) for the geometric mean titer (GMT) ratio being greater than 0.5. Our search returned 2464 studies, of which 23 were included in data analyses. When evaluated against standard schedules, although robust immunogenicity was demonstrated across all multi-dose groups, non-inferiority of extended interval dosing was mixed across vaccines, subtypes, and time points. Single dose did not meet the criteria for non-inferiority in any comparisons. Sparse data limited the number of possible comparisons, and further research is warranted. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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10 pages, 1532 KiB

Open AccessBrief Report

Intranasal Delivery of a Chitosan-Hydrogel Vaccine Generates Nasal Tissue Resident Memory CD8⁺ T Cells That Are Protective against Influenza Virus Infection

by James G. Bedford, Irina Caminschi and Linda M. Wakim

Vaccines 2020, 8(4), 572; https://doi.org/10.3390/vaccines8040572 - 1 Oct 2020

Cited by 31 | Viewed by 4641

Abstract

Rapid antigen clearance from the nasal mucosa is one of the major challenges in the development of intranasal vaccines. Here, we tested whether intranasal immunization with a chitosan-hydrogel vaccine, with in situ gelling properties, extended antigen retention time within the nasal mucosa. Intranasal [...] Read more.

Rapid antigen clearance from the nasal mucosa is one of the major challenges in the development of intranasal vaccines. Here, we tested whether intranasal immunization with a chitosan-hydrogel vaccine, with in situ gelling properties, extended antigen retention time within the nasal mucosa. Intranasal immunization with a chitosan-hydrogel vaccine retained antigen within the upper respiratory tract (URT), while intranasal delivery of less viscous vaccines led to antigen accumulation within the lower airways. Interestingly, sustained antigen retention within the URT following chitosan-hydrogel vaccination boosted the number of vaccine-specific, tissue resident memory (Trm) CD8⁺ T cells that developed within the nasal mucosa. Mice immunized with a chitosan-hydrogel vaccine loaded with influenza virus peptides developed a large pool of influenza-specific CD8⁺ nasal Trm and these cells were highly protective during an influenza challenge. Our results describe an effective vaccine formulation that can be utilized to boost local immunity in the nasal mucosa. Full article

(This article belongs to the Special Issue Evaluation of Vaccine Immunogenicity)

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