Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates

Abstract

Second-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen Modified Vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.

Single immunization with recombinant ACAM2000 vaccinia viruses expressing the spike and the nucleocapsid proteins protect hamsters against SARS-CoV-2 caused clinical disease

“…Several studies have reported that a recombinant MVA expressing the S protein induced protective immune responses in transgenic mice expressing human ACE2 and in non human primate (NHP) model [11][12][13][14] . More recently, a recombinant MVA expressing both the S and N proteins was shown to induce neutralizing antibody and cell-mediated immune responses 16 and was protective against SARS-CoV-2 challenge in hamsters and NHPs 17 . Although MVA is well known for its safety record and capacity to express foreign proteins, Its immunogenicity is lower than the first generation of VACV 27,[45][46][47] .…”

“…Conserved T-cell epitopes in the N protein have been identified among SARS-CoV-2 variants and these epitopes may induce cross-protective immune responses against a wide range of emerging variants of SARS-CoV-2 50,51 . Several studies have demonstrated that the N protein vaccine candidates based on different platforms induced protection against SARS-CoV-2 infection 17,[52][53][54][55][56] . In this study, we constructed three novel rACAM2000 based COVID-19 vaccine candidates: rACAM2000S, rACAM2000N and rACAM2000SN.…”

“…Thus, our study clearly demonstrates that the immune responses induced by the N protein contribute to the overall protective efficacy. A recombinant COVID-19 vaccine candidate based on MVA expressing both the S and N proteins was shown to protect hamsters against SARS-CoV-2 infection after two doses of vaccination 17 . It would be valuable for the future design of recombinant VACV based COVID-19 vaccines to compare the protective efficacies of the recombinant MVA 17 and the rACAM2000 (described in this study) vaccine candidates expressing both the S and N proteins.…”

“…A recombinant COVID-19 vaccine candidate based on MVA expressing both the S and N proteins was shown to protect hamsters against SARS-CoV-2 infection after two doses of vaccination 17 . It would be valuable for the future design of recombinant VACV based COVID-19 vaccines to compare the protective efficacies of the recombinant MVA 17 and the rACAM2000 (described in this study) vaccine candidates expressing both the S and N proteins. It is interesting to note that the effect from immunization with rACAM2000N on the viral load in the distal tissues, e.g.…”

“…Due to its safety record, the highly attenuated VACV strain, modified vaccinia Ankara (MVA), has been the most widely used vaccinia vector 10 . Currently, several MVA based COVID-19 vaccine candidates have been reported [11][12][13][14][15][16][17] . VACV ACAM2000 is another FDA-licensed smallpox vaccine and was derived by plaquepurification from the VACV NYCBH strain 18 , one of the main vaccines used in the eradication of smallpox.…”