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18 pages, 3546 KiB

Open AccessArticle

Oral and Subcutaneous Immunization with a Plant-Produced Mouse-Specific Zona Pellucida 3 Peptide Presented on Hepatitis B Core Antigen Virus-like Particles

by Khadijeh Ghasemian, Inge Broer, Jennifer Schön, Richard Killisch, Nadine Kolp, Armin Springer and Jana Huckauf

Vaccines 2023, 11(2), 462; https://doi.org/10.3390/vaccines11020462 - 17 Feb 2023

Cited by 1 | Viewed by 1921

Abstract

A short mouse-specific peptide from zona pellucida 3 (mZP3, amino acids 328–342) has been shown to be associated with antibody-mediated contraception. In this study, we investigated the production of mZP3 in the plant, as an orally applicable host, and examined the immunogenicity of [...] Read more.

A short mouse-specific peptide from zona pellucida 3 (mZP3, amino acids 328–342) has been shown to be associated with antibody-mediated contraception. In this study, we investigated the production of mZP3 in the plant, as an orally applicable host, and examined the immunogenicity of this small peptide in the BALB/c mouse model. The mZP3 peptide was inserted into the major immunodominant region of the hepatitis B core antigen and was produced in Nicotiana benthamiana plants via Agrobacterium-mediated transient expression. Soluble HBcAg-mZP3 accumulated at levels up to 2.63 mg/g leaf dry weight (LDW) containing ~172 µg/mg LDW mZP3 peptide. Sucrose gradient analysis and electron microscopy indicated the assembly of the HBcAg-mZP3 virus-like particles (VLPs) in the soluble protein fraction. Subcutaneously administered mZP3 peptide displayed on HBcAg VLPs was immunogenic in BALB/c mice at a relatively low dosage (5.5 µg mZP3 per dose) and led to the generation of mZP3-specific antibodies that bound to the native zona pellucida of wild mice. Oral delivery of dried leaves expressing HBcAg-mZP3 also elicited mZP3-specific serum IgG and mucosal IgA that cross-reacted with the zona pellucida of wild mice. According to these results, it is worthwhile to investigate the efficiency of plants producing HBcAg-mZP3 VLPs as immunogenic edible baits in reducing the fertility of wild mice through inducing antibodies that cross-react to the zona pellucida. Full article

(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles-2nd Edition)

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16 pages, 2497 KiB

Open AccessArticle

A cVLP-Based Vaccine Displaying Full-Length PCSK9 Elicits a Higher Reduction in Plasma PCSK9 Than Similar Peptide-Based cVLP Vaccines

by Louise Goksøyr, Magdalena Skrzypczak, Maureen Sampson, Morten A. Nielsen, Ali Salanti, Thor G. Theander, Alan T. Remaley, Willem A. De Jongh and Adam F. Sander

Vaccines 2023, 11(1), 2; https://doi.org/10.3390/vaccines11010002 - 20 Dec 2022

Cited by 5 | Viewed by 1832

Abstract

Administration of PCSK9-specific monoclonal antibodies, as well as peptide-based PCSK9 vaccines, can lower plasma LDL cholesterol by blocking PCSK9. However, these treatments also cause an increase in plasma PCSK9 levels, presumably due to the formation of immune complexes. Here, we utilize a versatile [...] Read more.

Administration of PCSK9-specific monoclonal antibodies, as well as peptide-based PCSK9 vaccines, can lower plasma LDL cholesterol by blocking PCSK9. However, these treatments also cause an increase in plasma PCSK9 levels, presumably due to the formation of immune complexes. Here, we utilize a versatile capsid virus-like particle (cVLP)-based vaccine platform to deliver both full-length (FL) PCSK9 and PCSK9-derived peptide antigens, to investigate whether induction of a broader polyclonal anti-PCSK9 antibody response would mediate more efficient clearance of plasma PCSK9. This head-to-head immunization study reveals a significantly increased capacity of the FL PCSK9 cVLP vaccine to opsonize and clear plasma PCSK9. These findings may have implications for the design of PCSK9 and other vaccines that should effectively mediate opsonization and immune clearance of target antigens. Full article

(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles-2nd Edition)

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21 pages, 3617 KiB

Open AccessArticle

SARS-CoV-2 Subunit Virus-like Vaccine Demonstrates High Safety Profile and Protective Efficacy: Preclinical Study

by Anna V. Vakhrusheva, Aleksandr V. Kudriavtsev, Nickolay A. Kryuchkov, Roman V. Deev, Maria E. Frolova, Konstantin A. Blagodatskikh, Milana Djonovic, Andrey A. Nedorubov, Elena Odintsova, Aleksandr V. Ivanov, Ekaterina A. Romanovskaya-Romanko, Marina A. Stukova, Artur A. Isaev and Igor V. Krasilnikov

Vaccines 2022, 10(8), 1290; https://doi.org/10.3390/vaccines10081290 - 10 Aug 2022

Cited by 2 | Viewed by 2852

Abstract

Public health threat coming from a rapidly developing COVID-19 pandemic calls for developing safe and effective vaccines with innovative designs. This paper presents preclinical trial results of “Betuvax-CoV-2”, a vaccine developed as a subunit vaccine containing a recombinant RBD-Fc fusion protein and betulin-based [...] Read more.

Public health threat coming from a rapidly developing COVID-19 pandemic calls for developing safe and effective vaccines with innovative designs. This paper presents preclinical trial results of “Betuvax-CoV-2”, a vaccine developed as a subunit vaccine containing a recombinant RBD-Fc fusion protein and betulin-based spherical virus-like nanoparticles as an adjuvant (“Betuspheres”). The study aimed to demonstrate vaccine safety in mice, rats, and Chinchilla rabbits through acute, subchronic, and reproductive toxicity studies. Along with safety, the vaccine demonstrated protective efficacy through SARS-CoV-2-neutralizing antibody production in mice, rats, hamsters, rabbits, and primates (rhesus macaque), and lung damage and infection protection in hamsters and rhesus macaque model. Eventually, “Betuvax-CoV-2” was proved to confer superior efficacy and protection against the SARS-CoV-2 in preclinical studies. Based on the above results, the vaccine was enabled to enter clinical trials that are currently underway. Full article

(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles-2nd Edition)

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19 pages, 3118 KiB

Open AccessArticle

Epitope-Based Vaccines against the Chlamydia trachomatis Major Outer Membrane Protein Variable Domain 4 Elicit Protection in Mice

by Amanda L. Collar, Alexandria C. Linville, Susan B. Core and Kathryn M. Frietze

Vaccines 2022, 10(6), 875; https://doi.org/10.3390/vaccines10060875 - 30 May 2022

Cited by 7 | Viewed by 3242

Abstract

Chlamydia trachomatis (Ct) is the most common bacterial sexual transmitted pathogen, yet a vaccine is not currently available. Here, we used the immunogenic bacteriophage MS2 virus-like particle (VLP) technology to engineer vaccines against the Ct major outer membrane protein variable domain 4 (MOMP-VD4), [...] Read more.

Chlamydia trachomatis (Ct) is the most common bacterial sexual transmitted pathogen, yet a vaccine is not currently available. Here, we used the immunogenic bacteriophage MS2 virus-like particle (VLP) technology to engineer vaccines against the Ct major outer membrane protein variable domain 4 (MOMP-VD4), which contains a conserved neutralizing epitope (TTLNPTIAG). A previously described monoclonal antibody to the MOMP-VD4 (E4 mAb) is capable of neutralizing all urogenital Ct serovars and binds this core epitope, as well as several non-contiguous amino acids. This suggests that this core epitope may require conformational context in order to elicit neutralizing antibodies to Ct. In order to identify immunogens that could elicit neutralizing antibodies to the TTLNPTIAG epitope, we used two approaches. First, we used affinity selection with a bacteriophage MS2-VLP library displaying random peptides in a constrained, surface-exposed loop to identify potential E4 mAb mimotopes. After four rounds of affinity selection, we identified a VLP-displayed peptide (HMVGSTKWTN) that could bind to the E4 mAb and elicited serum IgG that bound weakly to Ct elementary bodies by ELISA. Second, two versions of the core conserved TTLNPTIAG epitope (TTLNPTIAG and TTLNPTIAGA) were recombinantly expressed on the coat protein of the MS2 VLP in a constrained, surface-exposed loop. Mouse immune sera IgG bound to Ct elementary bodies by ELISA. Immunization with these MS2 VLPs provided protection from vaginal Chlamydia infection in a murine challenge model. These data suggest that short peptide epitopes targeting the MOMP-VD4 could be appropriate for Ct vaccine design when displayed on an immunogenic bacteriophage VLP vaccine platform. Full article

(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles-2nd Edition)

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14 pages, 2685 KiB

Open AccessArticle

Transdermal Immunization with Microparticulate RSV-F Virus-like Particles Elicits Robust Immunity

by Sucheta D’Sa, Kimberly Braz Gomes, Grace Lovia Allotey-Babington, Cemil Boyoglu, Sang-Moo Kang and Martin J. D’Souza

Vaccines 2022, 10(4), 584; https://doi.org/10.3390/vaccines10040584 - 10 Apr 2022

Cited by 2 | Viewed by 1995

Abstract

No approved vaccines against respiratory syncytial virus (RSV) infections exist to date, due to challenges arising during vaccine development. There is an unmet need to explore novel approaches and a universal strategy to prevent RSV infections. Previous studies have proven the immune efficacy [...] Read more.

No approved vaccines against respiratory syncytial virus (RSV) infections exist to date, due to challenges arising during vaccine development. There is an unmet need to explore novel approaches and a universal strategy to prevent RSV infections. Previous studies have proven the immune efficacy of virus-like particles (VLPs) consisting of RSV fusion (F) protein, yielding a highly immunogenic RSV-F VLP subunit vaccine. In this study, RSV-F VLP (with or without MPL^®) was added to a polymer mix and spray-dried, forming microparticles. The formulations were transdermally administered in C57BL/6 mice to evaluate vaccine efficacy. The transdermal delivery of RSV-F VLP + MPL^® was more effective in clearing lung viral loads and preventing weight loss after RSV challenge. At the cellular level, MPL^® augmented the vaccine response in microparticulate form, which was evidenced by higher serum and lung antibody titers, and lower lung viral titers in the vaccinated groups. These preliminary results validate the effectiveness of the RSV-F VLP microparticulate vaccine via the transdermal route due to its potential to trigger robust immune responses. Full article

(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles-2nd Edition)

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11 pages, 2058 KiB

Open AccessArticle

Induction of Broadly Cross-Reactive Antibodies by Displaying Receptor Binding Domains of SARS-CoV-2 on Virus-like Particles

by Xinyue Chang, Xuelan Liu, Mona O. Mohsen, Andris Zeltins, Byron Martina, Monique Vogel and Martin F. Bachmann

Vaccines 2022, 10(2), 307; https://doi.org/10.3390/vaccines10020307 - 16 Feb 2022

Cited by 4 | Viewed by 2481

Abstract

The impact of the COVID-19 pandemic has been reduced since the application of vaccination programs, mostly shown in the reduction of hospitalized patients. However, the emerging variants, in particular Omicron, have caused a steep increase in the number of infections; this increase is, [...] Read more.

The impact of the COVID-19 pandemic has been reduced since the application of vaccination programs, mostly shown in the reduction of hospitalized patients. However, the emerging variants, in particular Omicron, have caused a steep increase in the number of infections; this increase is, nevertheless, not matched by an increase in hospitalization. Therefore, a vaccine that induces cross-reactive antibodies against most or all variants is a potential solution for the issue of emerging new variants. Here, we present a vaccine candidate which displays receptor-binding domain (RBD) of SARS-CoV-2 on virus-like particles (VLP) that, in mice, not only induce strong antibody responses against RBD but also bind RBDs from other variants of concern (VOCs). The antibodies induced by wild-type (wt) RBD displayed on immunologically optimized Cucumber mosaic virus incorporated tetanus toxin (CuMV_TT) VLPs bind to wt as well as RBDs of VOCs with high avidities, indicating induction of strongly cross-reactive IgG antibodies. Interestingly, similar cross-reactive IgA antibodies were induced in immunized mice. Furthermore, these cross-reactive antibodies demonstrated efficacy in neutralizing wt (Wuhan) as well as SARS-CoV-2 VOCs (Beta, Delta, and Gamma). In summary, RBDs displayed on VLPs are capable of inducing protective cross-reactive IgG and IgA antibodies in mice, indicating that it may be possible to cover emerging VOCs with a single vaccine based on wt RBD. Full article

(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles-2nd Edition)

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15 pages, 3674 KiB

Open AccessArticle

Immunogenicity of Multi-Target Chimeric RHDV Virus-Like Particles Delivering Foreign B-Cell Epitopes

by María Zamora-Ceballos, Noelia Moreno, David Gil-Cantero, José R. Castón, Esther Blanco and Juan Bárcena

Vaccines 2022, 10(2), 229; https://doi.org/10.3390/vaccines10020229 - 2 Feb 2022

Cited by 5 | Viewed by 2039

Abstract

The rabbit hemorrhagic disease virus (RHDV) vaccine platform is a nanoparticle composed of 180 copies of the viral capsid protein, VP60, self-assembled into virus-like particles (VLPs). RHDV VLPs are able to accept the simultaneous incorporation of target epitopes at different insertion sites. The [...] Read more.

The rabbit hemorrhagic disease virus (RHDV) vaccine platform is a nanoparticle composed of 180 copies of the viral capsid protein, VP60, self-assembled into virus-like particles (VLPs). RHDV VLPs are able to accept the simultaneous incorporation of target epitopes at different insertion sites. The resulting chimeric RHDV VLPs displaying immunogenic foreign antigens have been shown to induce specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes in the mouse and pig models. In this study, we explored whether RHDV-based engineered VLPs can be developed as efficient multivalent vaccines co-delivering different foreign B-cell antigens. We generated bivalent chimeric RHDV VLPs displaying two model B-cell epitopes at different surface-exposed insertion sites, as well as the corresponding monovalent chimeric VLPs. The immunogenic potential of the bivalent chimeric VLPs versus the monovalent constructs was assessed in the mouse model. We found that the bivalent chimeric VLPs elicited a strong and balanced antibody response towards the two target epitopes tested, although slight reductions were observed in the levels of specific serum antibody titers induced by bivalent chimeric VLPs as compared with the corresponding monovalent constructs. These results suggest that RHDV VLPs could represent a promising platform for the development of efficient multivalent vaccines. Full article

(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles-2nd Edition)

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Review

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17 pages, 2363 KiB

Open AccessReview

Self-Assembling Protein Nanoparticles in the Design of Vaccines: 2022 Update

by Sergio Morales-Hernández, Nerea Ugidos-Damboriena and Jacinto López-Sagaseta

Vaccines 2022, 10(9), 1447; https://doi.org/10.3390/vaccines10091447 - 2 Sep 2022

Cited by 5 | Viewed by 3291

Abstract

Vaccines constitute a pillar in the prevention of infectious diseases. The unprecedented emergence of novel immunization strategies due to the COVID-19 pandemic has again positioned vaccination as a pivotal measure to protect humankind and reduce the clinical impact and socioeconomic burden worldwide. Vaccination [...] Read more.

Vaccines constitute a pillar in the prevention of infectious diseases. The unprecedented emergence of novel immunization strategies due to the COVID-19 pandemic has again positioned vaccination as a pivotal measure to protect humankind and reduce the clinical impact and socioeconomic burden worldwide. Vaccination pursues the ultimate goal of eliciting a protective response in immunized individuals. To achieve this, immunogens must be efficiently delivered to prime the immune system and produce robust protection. Given their safety, immunogenicity, and flexibility to display varied and native epitopes, self-assembling protein nanoparticles represent one of the most promising immunogen delivery platforms. Currently marketed vaccines against the human papillomavirus, for instance, illustrate the potential of these nanoassemblies. This review is intended to provide novelties, since 2015, on the ground of vaccine design and self-assembling protein nanoparticles, as well as a comparison with the current emergence of mRNA-based vaccines. Full article

(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles-2nd Edition)

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20 pages, 1903 KiB

Open AccessReview

Virus-like Particles as Preventive and Therapeutic Cancer Vaccines

by Anna Lucia Tornesello, Maria Tagliamonte, Franco M. Buonaguro, Maria Lina Tornesello and Luigi Buonaguro

Vaccines 2022, 10(2), 227; https://doi.org/10.3390/vaccines10020227 - 2 Feb 2022

Cited by 30 | Viewed by 5181

Abstract

Virus-like particles (VLPs) are self-assembled viral protein complexes that mimic the native virus structure without being infectious. VLPs, similarly to wild type viruses, are able to efficiently target and activate dendritic cells (DCs) triggering the B and T cell immunities. Therefore, VLPs hold [...] Read more.

Virus-like particles (VLPs) are self-assembled viral protein complexes that mimic the native virus structure without being infectious. VLPs, similarly to wild type viruses, are able to efficiently target and activate dendritic cells (DCs) triggering the B and T cell immunities. Therefore, VLPs hold great promise for the development of effective and affordable vaccines in infectious diseases and cancers. Vaccine formulations based on VLPs, compared to other nanoparticles, have the advantage of incorporating multiple antigens derived from different proteins. Moreover, such antigens can be functionalized by chemical modifications without affecting the structural conformation or the antigenicity. This review summarizes the current status of preventive and therapeutic VLP-based vaccines developed against human oncoviruses as well as cancers. Full article

(This article belongs to the Special Issue Development of Vaccines Based on Virus-Like Particles-2nd Edition)

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