Induction of poxviral immunity by synthetic MVA-based dual-antigen COVID-19 vaccine COH04S1

The recent outbreak of monkeypox (MPXV) outside its endemic boundaries has attracted global attention and prompted world leaders to reserve millions of doses of the only approved third-generation smallpox/MPXV vaccine, Jynneos, which is based on the highly attenuated modified vaccinia Ankara (MVA) vector. We previously developed COH04S1, a multiantigen SARS-CoV-2 vaccine built on a synthetic MVA (sMVA) platform. COH04S1 was extensively tested for efficacy and immunogenicity in animal models, including non-human primates (NHP), and was found to be safe and to induce SARS-CoV-2-specific immunity in a Phase 1 clinical trial in healthy adults. Here we demonstrate that one or two vaccinations of NHP with either COH04S1 or sMVA elicit robust othopoxvirus-specific binding and neutralizing antibody responses. Furthermore, healthy adults vaccinated with COH04S1 at different dose levels develop robust othopoxvirus-specific humoral and cellular immune responses that are durable for over six months post-vaccination. Importantly, both COH04S1 and sMVA vaccinations induce elevated and sustained antibody responses to MPXV-proteins that are major targets of protective neutralizing antibodies. These results demonstrate that COH04S1 and sMVA are valuable vaccine candidates to stimulate robust orthopox/MPXV-specific humoral and cellular immunity.

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

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.

Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.Competing Interest StatementThe authors have declared no competing interest.View Full Text