Lack of Effects on Female Fertility or Pre- and Postnatal Development of Offspring in Rats after Exposure to AS03-adjuvanted Recombinant Plant-Derived Virus-Like Particle Vaccine Candidate for COVID-19

Although antivirals are important tools to control the SARS-CoV-2 infection, effective vaccines are essential to control the current pandemic. Plant-derived virus-like particle (VLP) vaccine candidates have previously demonstrated immunogenicity and efficacy against influenza. Here we report the immunogenicity and protection induced in macaques by intramuscular injections of VLP bearing SARS-CoV-2 spike protein (CoVLP) vaccine candidate formulated with or without Adjuvant System 03 (AS03) or cytosine phosphoguanine (CpG) 1018. Although a single dose of unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses, booster immunization (at 28 days after prime) and adjuvants significantly improved both responses with a higher immunogenicity and protection provided by AS03 adjuvanted CoVLP. Fifteen microgram CoVLP adjuvanted with AS03 induced a balanced IL-2 driven response along with IL-4 expression in CD4 T cells and mobilization of CD4 follicular helper cells (Tfh). Animals were challenged by multiple routes (i.e. intratracheal, intranasal and ocular) with a total viral dose of 106 plaque forming units of SARS-CoV-2. Lower viral replication in nasal swabs and broncho-alveolar lavage (BAL) as well as fewer SARS-CoV-2 infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of pro-inflammatory cytokines and chemotactic factors in BAL were observed in the animals immunized with CoVLP adjuvanted with AS03. No clinical, pathologic or virologic evidences of vaccine associated enhanced disease (VAED) were observed in vaccinated animals. CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.

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Safety, immunogenicity, and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman primates

Cellular and Molecular Immunology ◽

10.1038/s41423-021-00809-2 ◽

2022 ◽

Author(s):

Stéphane Pillet ◽

Prabhu S. Arunachalam ◽

Guadalupe Andreani ◽

Nadia Golden ◽

Jane Fontenot ◽

...

Keyword(s):

Immune Cell ◽

Vaccine Development ◽

Vaccine Candidate ◽

Rhesus Macaques ◽

Interleukin 2 ◽

Lavage Fluid ◽

Booster Immunization ◽

Recombinant Plant ◽

Virus Like Particle ◽

Multiple Routes

AbstractAlthough antivirals are important tools to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, effective vaccines are essential to control the current coronavirus disease 2019 (COVID-19) pandemic. Plant-derived virus-like particle (VLP) vaccine candidates have previously demonstrated immunogenicity and efficacy against influenza. Here, we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a VLP bearing a SARS-CoV-2 spike protein (CoVLP) vaccine candidate formulated with or without Adjuvant System 03 (AS03) or cytidine-phospho-guanosine (CpG) 1018. Although a single dose of the unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses, booster immunization (at 28 days after priming) and adjuvant administration significantly improved both responses, with higher immunogenicity and protection provided by the AS03-adjuvanted CoVLP. Fifteen micrograms of CoVLP adjuvanted with AS03 induced a polyfunctional interleukin-2 (IL-2)-driven response and IL-4 expression in CD4 T cells. Animals were challenged by multiple routes (i.e., intratracheal, intranasal, and ocular) with a total viral dose of 106 plaque-forming units of SARS-CoV-2. Lower viral replication in nasal swabs and bronchoalveolar lavage fluid (BALF) as well as fewer SARS-CoV-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CoVLP adjuvanted with AS03. No clinical, pathologic, or virologic evidence of vaccine-associated enhanced disease was observed in vaccinated animals. The CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.

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Immunogenicity and Protective Effect of a Virus-Like Particle Containing the SAG1 Antigen of Toxoplasma gondii as a Potential Vaccine Candidate for Toxoplasmosis

Biomedicines ◽

10.3390/biomedicines8040091 ◽

2020 ◽

Vol 8 (4) ◽

pp. 91

Author(s):

Won Hyung Choi ◽

Ji Sun Park

Keyword(s):

Toxoplasma Gondii ◽

Vaccine Candidate ◽

Survival Rates ◽

Pcr Analysis ◽

Antigen Delivery ◽

Strong Activity ◽

Western Blot Method ◽

Cytokine Analysis ◽

Virus Like Particle ◽

Potential Vaccine

This study was carried out to evaluate the vaccination effect of a virus-like particle (VLP) including the surface antigen 1 (SAG1) of Toxoplasma gondii as a potential vaccine for toxoplasmosis. The SAG1 virus-like particles (SAG1-VLPs) were expressed by Sf9 cells, and their expression was confirmed through cloning, RT-PCR analysis, and western blot method. The immunogenicity and vaccine efficacy of SAG1-VLPs were assessed by the antibody response, cytokine analysis, neutralization activity, splenocyte assay, and survival rates through a mouse model. In particular, IgG, IgG1, IgG2a, and IgA were markedly increased after immunization, and the survival rates of T. gondii were strongly inhibited by the immunized sera. Furthermore, the immunization of SAG1-VLPs effectively decreased the production of specific cytokines, such as IL-1β, IL-6, TNF-α, and IFN-γ, after parasite infection. In particular, the immunized group showed strong activity and viability compared with the non-immunized infection group, and their survival rate was 75%. These results demonstrate that SAG1-VLP not only has the immunogenicity to block T. gondii infection by effectively inducing the generation of specific antibodies against T. gondii, but is also an effective antigen delivery system for preventing toxoplasmosis. This study indicates that SAG1-VLP can be effectively utilized as a promising vaccine candidate for preventing or inhibiting T. gondii infection.

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Persistence of Antibodies to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: 1-Year Follow-up With Memory Probe Vaccination

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz170 ◽

2019 ◽

Vol 220 (4) ◽

pp. 603-614 ◽

Cited By ~ 6

Author(s):

Robert L Atmar ◽

Frank Baehner ◽

Jakob P Cramer ◽

Eric Lloyd ◽

James Sherwood ◽

...

Keyword(s):

Vaccine Candidate ◽

Immunoglobulin A ◽

Primary Vaccination ◽

Immune Memory ◽

Virus Like Particle ◽

Memory Probe ◽

Antibody Titers ◽

Antibody Levels ◽

With Memory

AbstractBackgroundWe previously reported the tolerability and immunogenicity 1 month after intramuscular administration of 2 bivalent virus-like particle (VLP)–based candidate norovirus vaccine formulations in adults. We now describe the persistence of immunity and responses to a memory probe vaccination 1 year later.MethodsA total of 454 healthy men and women aged 18–49 years in 3 equal groups received placebo (saline) or 15/50 or 50/50 vaccine formulations (ie, 15 or 50 µg of GI.1 genotype VLPs, respectively, and 50 µg of GII.4c VLPs) with MPL and Al(OH)3. Immunogenicity and safety were assessed up to day 365, when 351 participants received a memory probe vaccination of 15 µg each of GI.1 and GII.4c VLPs with Al(OH)3.ResultsNo safety signals were detected up to 1 year after the first vaccination. Pan-immunoglobulin, immunoglobulin A, and histo-blood group antigen–blocking (HBGA) antibody levels among vaccinees waned but remained higher than levels before vaccination and levels in placebo recipients on days 180 and 365. Memory probe vaccination increased all antibody titers. Levels of HBGA antibodies to GI.1 but not GII.4c were higher after the first vaccination in candidate vaccine groups, compared with those in the placebo group.ConclusionLevels of antibodies to both candidate norovirus VLP formulations persisted above baseline levels for at least 1 year after primary vaccination. HBGA-blocking responses to the memory probe for GI.1 but not GII.4c displayed characteristics of immune memory.Clinical Trials RegistrationNCT02142504.

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Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial

The Journal of Infectious Diseases ◽

10.1093/infdis/jiw259 ◽

2016 ◽

Vol 214 (6) ◽

pp. 845-853 ◽

Cited By ~ 28

Author(s):

Robert L. Atmar ◽

Frank Baehner ◽

Jakob P. Cramer ◽

Eric Song ◽

Astrid Borkowski ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Vaccine Candidate ◽

Controlled Trial ◽

Healthy Adults ◽

Randomized Controlled ◽

Rapid Responses ◽

Virus Like Particle

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Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate

10.1101/2020.05.18.099234 ◽

2020 ◽

Cited By ~ 1

Author(s):

Kajal Arora ◽

Ruchir Rastogi ◽

Nupur Mehrotra Arora ◽

Deepak Parashar ◽

Jeny Paliwal ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Self Assembly ◽

Vaccine Candidate ◽

Analytical Data ◽

Surface Coat ◽

Uniform Size ◽

Virus Surface ◽

Transmission Electron ◽

Virus Like Particle ◽

Uniform Size Distribution

AbstractSpike, Envelope and Membrane proteins from the SARS CoV-2 virus surface coat are important vaccine targets. We hereby report recombinant co-expression of the three proteins (Spike, Envelope and Membrane) in a engineered Saccharomyces cerevisiae platform (D-Crypt™) and their self-assembly as Virus-like particle (VLP). This design as a multi-antigenic VLP for SARS CoV-2 has the potential to be a scalable vaccine candidate. The VLP is confirmed by transmission electron microscopy (TEM) images of the SARS CoV-2, along with supportive HPLC, Dynamic Light Scattering (DLS) and allied analytical data. The images clearly outline the presence of a “Corona” like morphology, and uniform size distribution.

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Structural Characterization and Formulation Development of a Trivalent Equine Encephalitis Virus-Like Particle Vaccine Candidate

Journal of Pharmaceutical Sciences ◽

10.1016/j.xphs.2018.05.022 ◽

2018 ◽

Vol 107 (10) ◽

pp. 2544-2558 ◽

Cited By ~ 3

Author(s):

Vishal M. Toprani ◽

Yuan Cheng ◽

Newton Wahome ◽

Harshit Khasa ◽

Lisa A. Kueltzo ◽

...

Keyword(s):

Structural Characterization ◽

Vaccine Candidate ◽

Encephalitis Virus ◽

Formulation Development ◽

Equine Encephalitis Virus ◽

Virus Like Particle

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Single Dose of Bivalent H5 and H7 Influenza Virus-Like Particle Protects Chickens Against Highly Pathogenic H5N1 and H7N9 Avian Influenza Viruses

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.774630 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jiao Hu ◽

Peipei Peng ◽

Jun Li ◽

Qi Zhang ◽

Rumeng Li ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Avian Influenza ◽

Vaccine Candidate ◽

Influenza Viruses ◽

Avian Influenza Viruses ◽

Highly Pathogenic ◽

Virus Like Particle ◽

Inactivated Vaccines ◽

Pathogenic H5n1

Both H5N1 and H7N9 subtype avian influenza viruses cause enormous economic losses and pose considerable threats to public health. Bivalent vaccines against both two subtypes are more effective in control of H5N1 and H7N9 viruses in poultry and novel egg-independent vaccines are needed. Herein, H5 and H7 virus like particle (VLP) were generated in a baculovirus expression system and a bivalent H5+H7 VLP vaccine candidate was prepared by combining these two antigens. Single immunization of the bivalent VLP or commercial inactivated vaccines elicited effective antibody immune responses, including hemagglutination inhibition, virus neutralizing and HA-specific IgG antibodies. All vaccinated birds survived lethal challenge with highly pathogenic H5N1 and H7N9 viruses. Furthermore, the bivalent VLP significantly reduced viral shedding and virus replication in chickens, which was comparable to that observed for the commercial inactivated vaccine. However, the bivalent VLP was better than the commercial vaccine in terms of alleviating pulmonary lesions caused by H7N9 virus infection in chickens. Therefore, our study suggests that the bivalent H5+H7 VLP vaccine candidate can serve as a critical alternative for the traditional egg-based inactivated vaccines against H5N1 and H7N9 avian influenza virus infection in poultry.

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