Abstract
Self-amplifying RNA vaccines may induce equivalent or more potent immune responses at lower doses compared to non-replicating mRNA vaccines via amplified antigen expression. In this paper, we demonstrate that 1 μg of an LNP-formulated dual-antigen self-amplifying RNA vaccine (ZIP1642), encoding both the S-RBD and N antigen, elicits considerably higher neutralizing antibody titers against Wuhan-like Beta B.1.351 and Delta B.1.617.2 SARS-CoV-2 variants compared to those of convalescent patients. In addition, ZIP1642 vaccination in mice expanded both S- and N-specific CD3 + CD4 + and CD3 + CD8 + T cells and caused a Th1 shifted cytokine response. We demonstrate that the induction of such dual antigen-targeted cell-mediated immune response may provide better protection against variants displaying highly mutated Spike proteins, as infectious viral loads of both Wuhan-like and Beta variants were decreased after challenge of ZIP1642 vaccinated hamsters. Supported by these results, we encourage redirecting focus toward the induction of multiple antigen-targeted cell-mediated immunity in addition to neutralizing antibody responses to bypass waning antibody responses and attenuate infectious breakthrough and disease severity of future SARS-CoV-2 variants.
Keywords: COVID-19; COVID-19 vaccine; SARS-CoV-2; cell-mediated immunity; dual-antigen saRNA vaccine; self-amplifying RNA; variants of concern.
【저자키워드】 COVID-19, SARS-CoV-2, COVID-19 vaccine, variants of concern., Cell-mediated immunity, self-amplifying RNA, dual-antigen saRNA vaccine, 【초록키워드】 immune response, vaccination, spike, mRNA vaccine, hamsters, B.1.351, disease severity, Antibody Response, Th1, variant, SARS-CoV-2 variant, variants of concern, Delta, B.1.617.2, Proteins, CD4, CD8, T cell, Convalescent patients, SARS-CoV-2 variants, Viral load, mice, S-RBD, Beta, RNA vaccine, Neutralizing antibody response, Neutralizing antibody titer, cytokine response, lower dose, antigen expression, CD3, N antigen, amplified, caused, addition, elicit, induce, mutated, displaying, attenuate, cell-mediated immune, 【제목키워드】 Cellular immune response, SARS-CoV-2 variant, SARS-CoV-2 vaccine, RNA, humoral, PROTECT, induce,