Vaccines

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2 pages, 153 KiB

Open AccessEditorial

Research Updates for Influenza Virus and Vaccine Development

by Ewan P. Plant and Hang Xie

Vaccines 2021, 9(4), 383; https://doi.org/10.3390/vaccines9040383 - 14 Apr 2021

Viewed by 1976

Abstract

While the scientific community has been focusing on combating novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is responsible for the current COVID-19 pandemic, we also want to draw your attention to this Special Issue of Vaccines entitled “Influenza Virus and Vaccine [...] Read more.

While the scientific community has been focusing on combating novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is responsible for the current COVID-19 pandemic, we also want to draw your attention to this Special Issue of Vaccines entitled “Influenza Virus and Vaccine Development” [...] Full article

(This article belongs to the Special Issue Influenza Virus and Vaccine Development)

Research

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18 pages, 6364 KiB

Open AccessArticle

Correlation of Influenza B Haemagglutination Inhibiton, Single-Radial Haemolysis and Pseudotype-Based Microneutralisation Assays for Immunogenicity Testing of Seasonal Vaccines

by George W. Carnell, Claudia M. Trombetta, Francesca Ferrara, Emanuele Montomoli and Nigel J. Temperton

Vaccines 2021, 9(2), 100; https://doi.org/10.3390/vaccines9020100 - 28 Jan 2021

Cited by 6 | Viewed by 2378

Abstract

Influenza B is responsible for a significant proportion of the global morbidity, mortality and economic loss caused by influenza-related disease. Two antigenically distinct lineages co-circulate worldwide, often resulting in mismatches in vaccine coverage when vaccine predictions fail. There are currently operational issues with [...] Read more.

Influenza B is responsible for a significant proportion of the global morbidity, mortality and economic loss caused by influenza-related disease. Two antigenically distinct lineages co-circulate worldwide, often resulting in mismatches in vaccine coverage when vaccine predictions fail. There are currently operational issues with gold standard serological assays for influenza B, such as lack of sensitivity and requirement for specific antigen treatment. This study encompasses the gold standard assays with the more recent Pseudotype-based Microneutralisation assay in order to study comparative serological outcomes. Haemagglutination Inhibition, Single Radial Haemolysis and Pseudotype-based Microneutralisation correlated strongly for strains in the Yamagata lineage; however, it correlated with neither gold standard assays for the Victoria lineage. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccine Development)

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13 pages, 1157 KiB

Open AccessFeature PaperArticle

Mass Spectrometric Characterization of Narcolepsy-Associated Pandemic 2009 Influenza Vaccines

by Aditya Ambati, Guo Luo, Elora Pradhan, Jacob Louis, Ling Lin, Ryan D. Leib, Hanna Maria Ollila, Thomas Poiret, Christopher Adams and Emmanuel Mignot

Vaccines 2020, 8(4), 630; https://doi.org/10.3390/vaccines8040630 - 30 Oct 2020

Cited by 8 | Viewed by 3397

Abstract

The onset of narcolepsy, an irreversible sleep disorder, has been associated with 2009 influenza pandemic (pH1N1) infections in China, and with ASO3-adjuvanted pH1N1 vaccinations using Pandemrix in Europe. Intriguingly, however, the increased incidence was only observed following vaccination with Pandemrix but not Arepanrix [...] Read more.

The onset of narcolepsy, an irreversible sleep disorder, has been associated with 2009 influenza pandemic (pH1N1) infections in China, and with ASO3-adjuvanted pH1N1 vaccinations using Pandemrix in Europe. Intriguingly, however, the increased incidence was only observed following vaccination with Pandemrix but not Arepanrix in Canada. In this study, the mutational burden of actual vaccine lots of Pandemrix (n = 6) and Arepanrix (n = 5) sourced from Canada, and Northern Europe were characterized by mass spectrometry. The four most abundant influenza proteins across both vaccines were nucleoprotein NP, hemagglutinin HA, matrix protein M1, with the exception that Pandemrix harbored a significantly increased proportion of neuraminidase NA (7.5%) as compared to Arepanrix (2.6%). Most significantly, 17 motifs in HA, NP, and M1 harbored mutations, which significantly differed in Pandemrix versus Arepanrix. Among these, a 6-fold higher deamidation of HA146 (p.Asn146Asp) in Arepanrix was found relative to Pandemrix, while NP257 (p.Thr257Ala) and NP424 (p.Thr424Ile) were increased in Pandemrix. DQ0602 binding and tetramer analysis with mutated epitopes were conducted in Pandemrix-vaccinated cases versus controls but were unremarkable. Pandemrix harbored lower mutational burden than Arepanrix, indicating higher similarity to wild-type 2009 pH1N1, which could explain differences in narcolepsy susceptibility amongst the vaccines. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccine Development)

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14 pages, 3199 KiB

Open AccessArticle

Development and Evaluation of Vero Cell-Derived Master Donor Viruses for Influenza Pandemic Preparedness

by Po-Ling Chen, Tsai-Teng Tzeng, Alan Yung-Chih Hu, Lily Hui-Ching Wang and Min-Shi Lee

Vaccines 2020, 8(4), 626; https://doi.org/10.3390/vaccines8040626 - 25 Oct 2020

Cited by 4 | Viewed by 3153

Abstract

The embryonated egg-based platform currently produces the majority of seasonal influenza vaccines by employing a well-developed master donor virus (MDV, A/PR/8/34 (PR8)) to generate high-growth reassortants (HGRs) for A/H1N1 and A/H3N2 subtypes. Although the egg-based platform can supply enough seasonal influenza vaccines, it [...] Read more.

The embryonated egg-based platform currently produces the majority of seasonal influenza vaccines by employing a well-developed master donor virus (MDV, A/PR/8/34 (PR8)) to generate high-growth reassortants (HGRs) for A/H1N1 and A/H3N2 subtypes. Although the egg-based platform can supply enough seasonal influenza vaccines, it cannot meet surging demands during influenza pandemics. Therefore, multi-purpose platforms are desirable for pandemic preparedness. The Vero cell-based production platform is widely used for human vaccines and could be a potential multi-purpose platform for pandemic influenza vaccines. However, many wild-type and egg-derived influenza viruses cannot grow efficiently in Vero cells. Therefore, it is critical to develop Vero cell-derived high-growth MDVs for pandemic preparedness. In this study, we evaluated two in-house MDVs (Vero-15 and VB5) and two external MDVs (PR8 and PR8-HY) to generate Vero cell-derived HGRs for five avian influenza viruses (AIVs) with pandemic potentials (H5N1 clade 2.3.4, H5N1 clade 2.3.2.1, American-lineage H5N2, H7N9 first wave and H7N9 fifth wave). Overall, no single MDV could generate HGRs for all five AIVs, but this goal could be achieved by employing two in-house MDVs (vB5 and Vero-15). In immunization studies, mice received two doses of Vero cell-derived inactivated H5N1 and H7N9 whole virus antigens adjuvanted with alum and developed robust antibody responses. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccine Development)

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15 pages, 2624 KiB

Open AccessArticle

Genetic Co-Administration of Soluble PD-1 Ectodomains Modifies Immune Responses against Influenza A Virus Induced by DNA Vaccination

by Pierre Tannig, Antonia Sophia Peter, Dennis Lapuente, Stephan Klessing, Anna Schmidt, Dominik Damm, Matthias Tenbusch, Klaus Überla and Vladimir Temchura

Vaccines 2020, 8(4), 570; https://doi.org/10.3390/vaccines8040570 - 1 Oct 2020

Cited by 6 | Viewed by 3020

Abstract

Due to the low efficacy and the need for seasonal adaptation of currently licensed influenza A vaccines, the importance of alternative vaccination strategies is increasingly recognized. Considering that DNA vaccines can be rapidly manufactured and readily adapted with novel antigen sequences, genetic vaccination [...] Read more.

Due to the low efficacy and the need for seasonal adaptation of currently licensed influenza A vaccines, the importance of alternative vaccination strategies is increasingly recognized. Considering that DNA vaccines can be rapidly manufactured and readily adapted with novel antigen sequences, genetic vaccination is a promising immunization platform. However, the applicability of different genetic adjuvants to this approach still represents a complex challenge. Immune checkpoints are a class of molecules involved in adaptive immune responses and germinal center reactions. In this study, we immunized mice by intramuscular electroporation with a DNA-vaccine encoding hemagglutinin (HA) and nucleoprotein (NP) of the influenza A virus. The DNA-vaccine was applied either alone or in combination with genetic adjuvants encoding the soluble ectodomains of programmed cell death protein-1 (sPD-1) or its ligand (sPD-L1). Co-administration of genetic checkpoint adjuvants did not significantly alter immune responses against NP. In contrast, sPD-1 co-electroporation elevated HA-specific CD4⁺ T cell responses, decreased regulatory CD4⁺ T cell pools, and modulated the IgG2a-biased HA antibody pattern towards an isotype-balanced IgG response with a trend to higher influenza neutralization in vitro. Taken together, our data demonstrate that a genetic DNA-adjuvant encoding soluble ectodomains of sPD-1 was able to modulate immune responses induced by a co-administered influenza DNA vaccine. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccine Development)

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17 pages, 2965 KiB

Open AccessArticle

Immunogenicity and Protective Efficacy of Influenza A DNA Vaccines Encoding Artificial Antigens Based on Conservative Hemagglutinin Stem Region and M2 Protein in Mice

by Sergei Bazhan, Denis Antonets, Ekaterina Starostina, Tatyana Ilyicheva, Olga Kaplina, Vasiliy Marchenko, Alexander Durymanov, Svetlana Oreshkova and Larisa Karpenko

Vaccines 2020, 8(3), 448; https://doi.org/10.3390/vaccines8030448 - 9 Aug 2020

Cited by 9 | Viewed by 3347

Abstract

Background: Development of a universal vaccine capable to induce antibody responses against a broad range of influenza virus strains attracts growing attention. Hemagglutinin stem and the exposed fragment of influenza virus M2 protein are promising targets for induction of cross-protective humoral and cell-mediated [...] Read more.

Background: Development of a universal vaccine capable to induce antibody responses against a broad range of influenza virus strains attracts growing attention. Hemagglutinin stem and the exposed fragment of influenza virus M2 protein are promising targets for induction of cross-protective humoral and cell-mediated response, since they contain conservative epitopes capable to induce antibodies and cytotoxic T lymphocytes (CTLs) to a wide range of influenza virus subtypes. Methods: In this study, we generated DNA vaccine constructs encoding artificial antigens AgH1, AgH3, and AgM2 designed on the basis of conservative hemagglutinin stem fragments of two influenza A virus subtypes, H1N1 and H3N2, and conservative M2 protein, and evaluate their immunogenicity and protective efficacy. To obtain DNA vaccine constructs, genes encoding the designed antigens were cloned into a pcDNA3.1 vector. Expression of the target genes in 293T cells transfected with DNA vaccine constructs has been confirmed by synthesis of specific mRNA. Results: Immunization of BALB/c mice with DNA vaccines encoding these antigens was shown to evoke humoral and T-cell immune responses as well as a moderated statistically significant cross-protective effect against two heterologous viruses A/California/4/2009 (H1N1pdm09) and A/Aichi/2/68 (H3N2). Conclusions: The results demonstrate a potential approach to creating a universal influenza vaccine based on artificial antigens. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccine Development)

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20 pages, 1868 KiB

Open AccessArticle

A Phase 1 Randomized Placebo-Controlled Study to Assess the Safety, Immunogenicity and Genetic Stability of a New Potential Pandemic H7N9 Live Attenuated Influenza Vaccine in Healthy Adults

by Irina Kiseleva, Irina Isakova-Sivak, Marina Stukova, Marianna Erofeeva, Svetlana Donina, Natalie Larionova, Elena Krutikova, Ekaterina Bazhenova, Ekaterina Stepanova, Kirill Vasilyev, Victoria Matyushenko, Marina Krylova, Julia Galatonova, Aleksey Ershov, Dmitry Lioznov, Erin Grace Sparrow, Guido Torelli and Larisa Rudenko

Vaccines 2020, 8(2), 296; https://doi.org/10.3390/vaccines8020296 - 10 Jun 2020

Cited by 5 | Viewed by 3157

Abstract

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of [...] Read more.

This study describes a double-blind randomized placebo-controlled phase I clinical trial in healthy adults of a new potential pandemic H7N9 live attenuated influenza vaccine (LAIV) based on the human influenza virus of Yangtze River Delta hemagglutinin lineage (ClinicalTrials.gov Identifier: NCT03739229). Two doses of H7N9 LAIV or placebo were administered intranasally to 30 and 10 subjects, respectively. The vaccine was well-tolerated and not associated with increased rates of adverse events or with any serious adverse events. Vaccine virus was detected in nasal swabs during the 6 days after vaccination or revaccination. A lower frequency of shedding was observed after the second vaccination. Twenty-five clinical viral isolates obtained after the first and second doses of vaccine retained the temperature-sensitive and cold-adapted phenotypic characteristics of LAIV. There was no confirmed transmission of the vaccine strain from vaccinees to placebo recipients. After the two H7N9 LAIV doses, an immune response was observed in 96.6% of subjects in at least one of the assays conducted. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccine Development)

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14 pages, 2799 KiB

Open AccessArticle

Recombinant Measles AIK-C Vaccine Strain Expressing Influenza HA Protein

by Takashi Ito, Takuji Kumagai, Yoshiaki Yamaji, Akihito Sawada and Tetsuo Nakayama

Vaccines 2020, 8(2), 149; https://doi.org/10.3390/vaccines8020149 - 27 Mar 2020

Cited by 9 | Viewed by 2809

Abstract

Recombinant measles AIK-C vaccine expressing the hemagglutinin (HA) protein of influenza A/Sapporo/107/2013(H1N1pdm) (MVAIK/PdmHA) was constructed. Measles particle agglutination (PA) and influenza hemagglutinin inhibition (HI) antibodies were induced in cotton rats immunized with MVAIK/PdmHA. Cotton rats immunized with two doses of the HA split [...] Read more.

Recombinant measles AIK-C vaccine expressing the hemagglutinin (HA) protein of influenza A/Sapporo/107/2013(H1N1pdm) (MVAIK/PdmHA) was constructed. Measles particle agglutination (PA) and influenza hemagglutinin inhibition (HI) antibodies were induced in cotton rats immunized with MVAIK/PdmHA. Cotton rats immunized with two doses of the HA split vaccine were used as positive controls, and higher HI antibodies were detected 3 weeks after the first dose. Following the challenge of A/California/07/2009(H1N1pdm), higher viral loads (10⁷ TCID50/g) were detected in the lung homogenates of cotton rats immunized with the empty vector (MVAIK) or control groups than those immunized with MVAIK/Pdm HA (10³ TCID50/g) or the group immunized with HA split vaccine (10⁵ TCID50/g). Histopathologically, destruction of the alveolar structure, swelling of broncho-epithelial cells, and thickening of the alveolar wall with infiltration of inflammatory cells and HA antigens were detected in lung tissues obtained from non-immunized rats and those immunized with the empty vector after the challenge, but not in those immunized with the HA spilt or MVAIK/PdmHA vaccine. Lower levels of IFN-α, IL-1β, and TNF-α mRNA, and higher levels of IFN-γ mRNA were found in the lung homogenates of the MVAIK/PdmHA group. Higher levels of IFN-γ mRNA were detected in spleen cell culture from the MVAIK/PdmHA group stimulated with UV-inactivated A/California/07/2009(H1N1pdm). In conclusion, the recombinant MVAIK vaccine expressing influenza HA protein induced protective immune responses in cotton rats. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccine Development)

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15 pages, 920 KiB

Open AccessCommentary

Pandemic Influenza Vaccines: What did We Learn from the 2009 Pandemic and are We Better Prepared Now?

by Steven Rockman, Karen Laurie and Ian Barr

Vaccines 2020, 8(2), 211; https://doi.org/10.3390/vaccines8020211 - 7 May 2020

Cited by 18 | Viewed by 3298

Abstract

In 2009, a novel A(H1N1) influenza virus emerged with rapid human-to-human spread and caused the first pandemic of the 21st century. Although this pandemic was considered mild compared to the previous pandemics of the 20^th century, there was still extensive disease and [...] Read more.

In 2009, a novel A(H1N1) influenza virus emerged with rapid human-to-human spread and caused the first pandemic of the 21st century. Although this pandemic was considered mild compared to the previous pandemics of the 20^th century, there was still extensive disease and death. This virus replaced the previous A(H1N1) and continues to circulate today as a seasonal virus. It is well established that vaccines are the most effective method to alleviate the mortality and morbidity associated with influenza virus infections, but the 2009 A(H1N1) influenza pandemic, like all significant infectious disease outbreaks, presented its own unique set of problems with vaccine supply and demand. This manuscript describes the issues that confronted governments, international agencies and industries in developing a well-matched vaccine in 2009, and identifies the key improvements and remaining challenges facing the world as the next influenza pandemic inevitably approaches. Full article

(This article belongs to the Special Issue Influenza Virus and Vaccine Development)

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