Enhanced antibody class switching and T cell responses to a self-amplifying RNA vs mRNA vaccine against SARS-CoV-2 spike protein 4547

Abstract Description RNA-based vaccines allow for rapid development and deployment. We evaluated immune responses over 1 yr in mice administered with two equivalent doses of a first generation self-amplifying RNA (saRNA) or mRNA vaccine encoding the SARS-CoV-2 spike protein. IgG1 concentrations were higher at 42 d post-vaccination in the mRNA group (mRNA: 2839.6 mg/mL, saRNA: 39.0 mg/mL; p < 0.001) without discernable differences in IgG2a, IgG3, or neutralizing antibody levels. At 180 d post-vaccination, the saRNA vaccinated group showed better retention of a neutralizing antibody response (saRNA: 87.6 mg/mL, mRNA: 32.8 mg/mL; p = 0.011), with elevated IgG3 titers (saRNA: 4.4 mg/mL, mRNA: 2.2 mg/mL; p = 0.031). One-year post-vaccination, saRNA vaccinated mice maintained elevated neutralizing antibody response (saRNA: 2.8 mg/mL, mRNA: 1.3 mg/mL; p = 0.015). Analysis of the B and T cell compartments at 42 d showed increased B cell antibody class switching (saRNA: 5.1%, mRNA: 4.3%; p = 0.033) and an increase in CD4+ cmT cells (saRNA: 1.7%, mRNA: 1.3%; p = 0.027) in the saRNA vaccinated cohort. scRNAseq analysis showed an increased inflammatory character of antigen-presenting cells at the injection site and a greater differentiation of cytotoxic CD8 T cells in the saRNA vs mRNA groups. These data provide evidence for an enhancement in humoral and cellular immunity by saRNA that may be beneficial in circumstances where antibody differentiation and antigen-experienced memory responses are desirable. Funding Sources Ludwig and Mathers Foundations Topic Categories Vaccines and Immunotherapy (VAC)