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Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2. CORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology. This study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.

SUBMITTER: Kurup D

PROVIDER: S-EPMC8023494 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity.

Project description:The objective of this study is to further analyze recombinant rabies virus-vectored SARS-CoV-2 vaccine, CORAVAX, as an effective COVID-19 vaccine strategy. CORAVAX has proven immunogenic and protective against SARS-CoV-2 in animal models. Here, we have screened adjuvants for the highest quality antibody titers, negated the concern of pre-existing rabies-vector immunity, and established its potential as a long-term COVID-19 vaccine. We have tested toll-like receptor 4 (TLR4) agonists, inflammasome activators, and alum adjuvants in CORAVAX and found TLR4-activating MPLA-AddaVax to have the greatest potential. We followed the humoral immune response to CORAVAX in mice with pre-existing rabies virus immunity and saw no significant differences compared to naive mice. We then followed the immune response to CORAVAX over several months and 1-year post-immunization. Mice maintained high antigen-specific serum antibody titers as well as long-lived antibody-secreting cells in the spleen and bone marrow. We believe this rabies-vector strategy combats the problem of waning immunity of other COVID-19 vaccines. These results together support CORAVAX's potential during the ongoing COVID-19 pandemic.

| S-EPMC9508099 | biostudies-literature

Immunogenicity and protective efficacy of BBV152, whole virion inactivated SARS- CoV-2 vaccine candidates in the Syrian hamster model.

Project description:The availability of a safe and effective vaccine would be the eventual measure to deal with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) threat. Here, we have assessed the immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidates BBV152A, BBV152B, and BBV152C in Syrian hamsters. Three dose vaccination regimes with vaccine candidates induced significant titers of SARS-CoV-2-specific IgG and neutralizing antibodies. BBV152A and BBV152B vaccine candidates remarkably generated a quick and robust immune response. Post-SARS-CoV-2 infection, vaccinated hamsters did not show any histopathological changes in the lungs. The protection of the hamster was evident by the rapid clearance of the virus from lower respiratory tract, reduced virus load in upper respiratory tract, absence of lung pathology, and robust humoral immune response. These findings confirm the immunogenic potential of the vaccine candidates and further protection of hamsters challenged with SARS-CoV-2. Of the three candidates, BBV152A showed the better response.

| S-EPMC7829205 | biostudies-literature

Inactivated Rabies Virus Vectored MERS-Coronavirus Vaccine Induces Protective Immunity in Mice, Camels, and Alpacas.

Project description:Middle East respiratory syndrome coronavirus (MERS-CoV) is an emergent coronavirus that has caused frequent zoonotic events through camel-to-human spillover. An effective camelid vaccination strategy is probably the best way to reduce human exposure risk. Here, we constructed and evaluated an inactivated rabies virus-vectored MERS-CoV vaccine in mice, camels, and alpacas. Potent antigen-specific antibody and CD8+ T-cell responses were generated in mice; moreover, the vaccination reduced viral replication and accelerated virus clearance in MERS-CoV-infected mice. Besides, protective antibody responses against both MERS-CoV and rabies virus were induced in camels and alpacas. Satisfyingly, the immune sera showed broad cross-neutralizing activity against the three main MERS-CoV clades. For further characterization of the antibody response induced in camelids, MERS-CoV-specific variable domains of heavy-chain-only antibody (VHHs) were isolated from immunized alpacas and showed potent prophylactic and therapeutic efficacies in the Ad5-hDPP4-transduced mouse model. These results highlight the inactivated rabies virus-vectored MERS-CoV vaccine as a promising camelid candidate vaccine.

| S-EPMC8842186 | biostudies-literature

Absence of Vaccine-enhanced Disease With Unexpected Positive Protection Against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by Inactivated Vaccine Given Within 3 Days of Virus Challenge in Syrian Hamster Model.

Project description:BackgroundMass vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing amidst widespread transmission during the coronavirus disease-2019 (COVID-19) pandemic. Disease phenotypes of SARS-CoV-2 exposure occurring around the time of vaccine administration have not been described.MethodsTwo-dose (14 days apart) vaccination regimen with formalin-inactivated whole virion SARS-CoV-2 in golden Syrian hamster model was established. To investigate the disease phenotypes of a 1-dose regimen given 3 days prior (D-3), 1 (D1) or 2 (D2) days after, or on the day (D0) of virus challenge, we monitored the serial clinical severity, tissue histopathology, virus burden, and antibody response of the vaccinated hamsters.ResultsThe 1-dose vaccinated hamsters had significantly lower clinical disease severity score, body weight loss, lung histology score, nucleocapsid protein expression in lung, infectious virus titers in the lung and nasal turbinate, inflammatory changes in intestines, and a higher serum neutralizing antibody or IgG titer against the spike receptor-binding domain or nucleocapsid protein when compared to unvaccinated controls. These improvements were particularly noticeable in D-3, but also in D0, D1, and even D2 vaccinated hamsters to varying degrees. No increased eosinophilic infiltration was found in the nasal turbinate, lung, and intestine after virus challenge. Significantly higher serum titer of fluorescent foci microneutralization inhibition antibody was detected in D1 and D2 vaccinated hamsters at day 4 post-challenge compared to controls despite undetectable neutralizing antibody titer.ConclusionsVaccination just before or soon after exposure to SARS-CoV-2 does not worsen disease phenotypes and may even ameliorate infection.

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Immunogenicity and efficacy of recombinant subunit SARS-CoV-2 vaccine candidate in the Syrian hamster model.

Project description:SARS-CoV-2 causes devastating impact on the human population and has become a major public health concern. The frequent emergence of SARS-CoV-2 variants of concern urges the development of safe and efficacious vaccine against SARS-CoV-2 variants. We developed a candidate vaccine Baiya SARS-CoV-2 Vax 1, based on SARS-CoV-2 receptor-binding domain (RBD) by fusing with the Fc region of human IgG. The RBD-Fc fusion was produced in Nicotiana benthamiana. Previously, we reported that this plant-produced vaccine is effective in inducing immune response in both mice and non-human primates. Here, the efficacy of our vaccine candidate was tested in Syrian hamster challenge model. Hamsters immunized with two intramuscular doses of Baiya SARS-CoV-2 Vax 1 induced neutralizing antibodies against SARS-CoV-2 and protected from SARS-CoV-2 challenge with reduced viral load in the lungs. These preliminary results demonstrate the ability of plant-produced subunit vaccine Baiya SARS-CoV-2 Vax 1 to provide protection against SARS-CoV-2 infection in hamsters.

| S-EPMC9744481 | biostudies-literature

Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response (Hamster Lung RNA-seq Data)

Project description:The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) variants and “anatomical escape” characteristics threaten the effectiveness of current coronavirus disease (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. In this study, we investigated immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants. Intranasal delivery of dNS1-RBD induced innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrained the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (IL-6, IL-1B, and IFN-γ) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden. To investigate the immune response, pathological process caused by SARS-CoV-2 Beta variants infection in Golden Hamster lung. Golden hamsters were vaccinated with dNS1-RBD vaccine at day0 and day 14, and 2 months later the vccinated hamster were challenged with SARS-CoV-2 Beta varians together with control group hamster. Then the lung samples were collected at 0, 1, 3, 5 post infection to sequence for the RNA-seq data, then performed gene expression analysis using data obtained from RNA-seq.

2023-05-28 | GSE228112 | GEO

Intranasal delivery of NS1-deleted influenza virus vectored COVID-19 vaccine restrains the SARS-CoV-2 inflammatory response (Hamster AMs ATAC-seq Data)

Project description:The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) variants and “anatomical escape” characteristics threaten the effectiveness of current coronavirus disease (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. In this study, we investigated immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants. Intranasal delivery of dNS1-RBD induced innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrained the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (IL-6, IL-1B, and IFN-γ) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden. To investigate the trainned-immunity of alveolar macrophage generated by dNS1-RBD vaccine in Golden Hamster, we vaccinated Golden Hamster with dNS1-RBD/dNS1-Vector/PBS and collect the alveolar macrophage samples to sequence for the ATAC-seq data 2 months post vaccinated. Then performed the differential peak and igv track visualization with this dataset.

2023-05-28 | GSE228111 | GEO

Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques.

Project description:Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways, as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal IgA and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T-cell responses, including tissue-resident memory cells in lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine.

| S-EPMC9164439 | biostudies-literature

A Single Dose of the Deactivated Rabies-Virus Vectored COVID-19 Vaccine, CORAVAX, Is Highly Efficacious and Alleviates Lung Inflammation in the Hamster Model.

Project description:Without sufficient herd immunity through either vaccination or natural infection, the coronavirus disease 2019 pandemic is unlikely to be controlled. Waning immunity with the currently approved vaccines suggests the need to evaluate vaccines causing the induction of long-term responses. Here, we report the immunogenicity and efficacy of our adjuvanted single-dose Rabies-vectored SARS-CoV-2 S1 vaccine, CORAVAX, in hamsters. CORAVAX induces high SARS-CoV-2 S1-specific and virus-neutralizing antibodies (VNAs) that prevent weight loss, viral loads, disease, lung inflammation, and the cytokine storm in hamsters. We also observed high Rabies VNA titers. In summary, CORAVAX is a promising dual-antigen vaccine candidate for clinical evaluation against SARS-CoV-2 and Rabies virus.

| S-EPMC9229041 | biostudies-literature

DNA Based Vaccine Expressing SARS-CoV-2 Spike-CD40L Fusion Protein Confers Protection Against Challenge in a Syrian Hamster Model.

Project description:SARS-CoV-2 infections present a tremendous threat to public health. Safe and efficacious vaccines are the most effective means in preventing the infections. A variety of vaccines have demonstrated excellent efficacy and safety around the globe. Yet, development of alternative forms of vaccines remains beneficial, particularly those with simpler production processes, less stringent storage conditions, and the capability of being used in heterologous prime/boost regimens which have shown improved efficacy against many diseases. Here we reported a novel DNA vaccine comprised of the SARS-CoV-2 spike protein fused with CD40 ligand (CD40L) serving as both a targeting ligand and molecular adjuvant. A single intramuscular injection in Syrian hamsters induced significant neutralizing antibodies 3-weeks after vaccination, with a boost substantially improving immune responses. Moreover, the vaccine also reduced weight loss and suppressed viral replication in the lungs and nasal turbinates of challenged animals. Finally, the incorporation of CD40L into the DNA vaccine was shown to reduce lung pathology more effectively than the DNA vaccine devoid of CD40L. These results collectively indicate that this DNA vaccine candidate could be further explored because of its efficacy and known safety profile.

| S-EPMC8789660 | biostudies-literature

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