Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters

Abstract

COVID-19 in humans is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that belongs to the beta family of coronaviruses. SARS-CoV-2 causes severe respiratory illness in 10–15% of infected individuals and mortality in 2–3%. Vaccines are urgently needed to prevent infection and to contain viral spread. Although several mRNA- and adenovirus-based vaccines are highly effective, their dependence on the “cold chain” transportation makes global vaccination a difficult task. In this context, a stable lyophilized vaccine may present certain advantages. Accordingly, establishing additional vaccine platforms remains vital to tackle SARS-CoV-2 and any future variants that may arise. Vaccinia virus (VACV) has been used to eradicate smallpox disease, and several attenuated viral strains with enhanced safety for human applications have been developed. We have generated two candidate SARS-CoV-2 vaccines based on two vaccinia viral strains, MVA and v-NY, that express full-length SARS-CoV-2 spike protein. Whereas MVA is growth-restricted in mammalian cells, the v-NY strain is replication-competent. We demonstrate that both candidate recombinant vaccines induce high titers of neutralizing antibodies in C57BL/6 mice vaccinated according to prime-boost regimens. Furthermore, our vaccination regimens generated TH1-biased immune responses in mice. Most importantly, prime-boost vaccination of a Syrian hamster infection model with MVA-S and v-NY-S protected the hamsters against SARS-CoV-2 infection, supporting that these two vaccines are promising candidates for future development. Finally, our vaccination regimens generated neutralizing antibodies that partially cross-neutralized SARS-CoV-2 variants of concern.

Poxvirus MVA Expressing SARS-CoV-2 S Protein Induces Robust Immunity and Protects Rhesus Macaques From SARS-CoV-2

“…There have been reports of adverse effects of MVA vectors expressing the SARS-CoV-1 S protein when tested in NHPs, with an antibody-dependent enhancement (ADE) effect after SARS-CoV-1 infection ( 62 ) and with liver damage in ferrets ( 63 ). However, such adverse events have not been observed in this NHP study or in any of the preclinical studies performed to date with MVA vectors expressing SARS-CoV-2 S antigens ( 15 – 22 ). This is likely related to the distinct biology of the SARS-CoV-2 infection and the antigenic nature of the viral protein components.…”

“…We and others have developed several COVID-19 vaccine candidates based on the poxvirus-modified vaccinia virus Ankara (MVA) vector expressing the S protein that have shown a potent immunogenicity profile and full efficacy in several animal models, such as mice ( 15 – 21 ), hamsters ( 22 ), and non-human primates (NHPs) ( 20 ). MVA is a highly attenuated strain of vaccinia virus, with a well-established safety, immunogenicity, and protective profile in preclinical and clinical research as a vaccine candidate against several infectious diseases and cancer ( 23 – 25 ).…”

A Single Dose of an MVA Vaccine Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Protein Neutralizes Variants of Concern and Protects Mice From a Lethal SARS-CoV-2 Infection

“…MVA vectors have shown excellent immunogenicity and efficacy in different animal models (33,34) and parental MVA has been approved by FDA and EMA as a vaccine against smallpox and monkeypox; also, recombinant MVA-BN-FILO has been approved as a combined vaccine against Ebola virus (35). Previous recent studies with MVA vectors expressing S protein have shown good immunogenicity and efficacy results against SARS-CoV-2 in mice, hamsters, and monkey models (10)(11)(12)(13)(14)(15). These studies were performed with MVA-based vaccine candidates expressing either a non-stabilized S protein (10,11,15) or a prefusion-stabilized S protein (13,14).…”

“…Among SARS-CoV-2 vaccine candidates, non-replicating modified vaccinia virus Ankara (MVA) poxvirus vector have shown excellent results in preclinical trials (10)(11)(12)(13)(14)(15). In fact, we have previously described that an MVA vector expressing a fulllength non-stabilized SARS-CoV-2 S protein (termed MVA-CoV2-S) induced potent SARS-CoV-2-specific T-cell and humoral immune responses in C57BL/6 mice, as well as full efficacy in K18-hACE2 transgenic mice, especially when two doses of the vaccine candidate were administered (11).…”

Natural and Experimental SARS-CoV-2 Infection in Domestic and Wild Animals

“…Hamsters, particularly Syrian golden hamsters, are the most promising pre-clinical model of SARS-CoV-2 due to their consistent clinical signs and ability to transmit the virus to other hamsters, combined with their relative ease of housing and handling in biocontainment facilities. Syrian golden hamsters have already been used extensively to gain insights into the basic science of SARS-CoV-2 pathogenesis [ 156 , 157 , 158 , 159 , 160 , 161 ] and to test therapeutic interventions [ 162 , 163 , 164 , 165 , 166 , 167 ] and vaccines [ 168 , 169 , 170 , 171 , 172 ]. Moreover, there is clear evidence that older Syrian golden hamsters and Roborovski hamsters develop respiratory disease and lung pathology that recapitulates the severe disease found in older COVID-19 patients, and therefore could be highly informative models [ 77 , 81 ].…”