Effect of the C12L, A35R, A40R, and A41L Genes of MVA Vector on the Immunogenicity of Recombinant MVA Expressing the SARS-CoV-2 Spike Protein.

Modified vaccinia virus Ankara (MVA) is a highly attenuated strain of vaccinia virus widely used as a recombinant vector in vaccine development. Several studies have shown that deletion of the C12L, A35R, A40R, and A41L genes from the MVA genome can enhance T-cell and/or humoral immune responses not only to MVA vector proteins, but also to incorporated recombinant antigens. Here, we generated recombinant MVA (rMVA) constructs expressing the SARS-CoV-2 Spike protein, each harboring a deletion of one of the C12L, A35R, A40R, or A41L genes, and compared the immune responses in mice vaccinated with these rMVAs. None of these deletions altered T-cell or humoral responses to the Spike protein. However, immunization of mice with rMVAs bearing deletions of the A40R or A41L genes resulted in increased titers of MVA-specific antibodies. Meanwhile, the examined deletions did not affect the T-cell response to MVA itself, with the exception of the C12L gene deletion, which reduced the number of interferon-producing cells in response to MVA-specific peptides.