MVA-CoV2-S Vaccine Candidate Neutralizes Distinct Variants of Concern and Protects Against SARS-CoV-2 Infection in Hamsters

Abstract

To control the coronavirus disease 2019 (COVID-19) pandemic and the emergence of different variants of concern (VoCs), novel vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed. In this study, we report the potent immunogenicity and efficacy induced in hamsters by a vaccine candidate based on a modified vaccinia virus Ankara (MVA) vector expressing a human codon optimized full-length SARS-CoV-2 spike (S) protein (MVA-S). Immunization with one or two doses of MVA-S elicited high titers of S- and receptor-binding domain (RBD)-binding IgG antibodies and neutralizing antibodies against parental SARS-CoV-2 and VoC alpha, beta, gamma, delta, and omicron. After SARS-CoV-2 challenge, MVA-S-vaccinated hamsters showed a significantly strong reduction of viral RNA and infectious virus in the lungs compared to the MVA-WT control group. Moreover, a marked reduction in lung histopathology was also observed in MVA-S-vaccinated hamsters. These results favor the use of MVA-S as a potential vaccine candidate for SARS-CoV-2 in clinical trials.

Intranasal administration of a single dose of MVA-based vaccine candidates against COVID-19 induced local and systemic immune responses and protects mice from a lethal SARS-CoV-2 infection

“…Here, we demonstrated with three recombinant MVA-based vaccine candidates expressing either the native or a prefusion-stabilized SARS-CoV-2 S protein that a single IN administration of each vaccine was quite effective to induce robust immunogenicity and to better control SARS-CoV-2 infection in mice. The higher immunogenicity and efficacy of the MVA-S(3P) vaccine candidate, in comparison to MVA-S or MVA-Δ-S, agreed with our reported observations in mice immunized intramuscularly ( 26 ) and extended our previous investigations showing that MVA-based vaccines administered intramuscularly induced potent SARS-CoV-2-specific T-cell and humoral immune responses in several animal models, and fully protected against SARS-CoV-2 infection ( 16 , 19 , 20 , 22 , 25 , 26 ). Interestingly, the IN administration of the MVA-based vaccine candidates elicited in mice systemic SARS-CoV-2-specific humoral and T-cell (spleen) immune responses as that seen with the intramuscular route ( 19 , 20 , 22 , 26 ).…”

“…The capacity of the sera obtained from C57BL/6 or K18-hACE2 immunized mice to neutralize live SARS-CoV-2 virus was measured using a microneutralization test (MNT) assay in a BSL-3 laboratory at the CNB-CSIC, as previously described ( 16 , 22 , 25 , 26 ). Serially twofold diluted serum samples in DMEM-2% fetal bovine serum (FBS) medium were incubated at a 1:1 ratio with 100 median tissue culture infectious dose 50 (TCID 50 ) of the SARS-CoV-2 MAD6 isolate (similar to the Wuhan strain but having the D614G mutation in the S protein) ( 37 ) in 96-well tissue culture plates for 1 h at 37°C.…”

“…In particular, we generated COVID-19 vaccine candidates based on the MVA vector expressing either a human codon optimized full-length native spike (S) protein (MVA-CoV2-S and MVA-Δ-CoV2-S) or a full-length S protein stabilized in the prefusion conformation [MVA-CoV2-S(3P)]. Intramuscular administration of one or two doses of these vaccine candidates induced potent SARS-CoV-2-specific T-cell and humoral immune responses in mice, hamsters, or rhesus macaques, as well as full protection against SARS-CoV-2 infection in those animal models ( 16 , 19 , 20 , 22 , 25 , 26 ).…”

“…Moreover, MVA has been approved as a smallpox vaccine in the United States, Canada, and the European Union. Recently, with the appearance of the COVID-19 pandemic, we and others have generated several MVA vectors expressing SARS-CoV-2 antigens that induce, upon intramuscular immunization, robust immune responses, both humoral and cellular, leading to high efficacy against SARS-CoV-2 in several animal models (mice, hamsters, and macaques) (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28). Moreover, a recent phase 1 clinical trial showed safety and immunogenicity of a synthetic MVA vector expressing the S and N proteins of SARS-CoV-2 (29).…”

Are Hamsters a Suitable Model for Evaluating the Immunogenicity of RBD-Based Anti-COVID-19 Subunit Vaccines?

“…Viral RNA is readily detectable in the respiratory tract and other tissues (e.g., in the small intestine), which may be useful for evaluating therapeutics and vaccines [ 5 ]. Because studies in hamsters can be completed quickly and in a cost-effective manner, there is an increasing interest in the use of hamsters for accessing vaccines [ 19 , 20 , 21 , 22 , 23 , 24 ].…”