OX40 boosts and sustains humoral and cellular immune responses to SARS-CoV-2 spike protein and RNA vaccinations
AAI Annual Meeting; May 6-10; Portland, OR. 2022
oregon; chiles; covid-19
To prevent SARS-CoV-2 infections and generate long-lasting immunity, vaccines need to generate both, a strong humoral immune response as well as viral-specific CD4 and CD8 T cells. Previous results from our lab have shown that immunization in the presence of an agonist antibody targeting OX40 led to higher antibody titers and increased numbers of antigen-specific CD4 and CD8 T cells. Using the same strategy, we explored the effect of OX40 co-stimulation in the prime and boost together with the SARS-CoV-2 spike protein + adjuvant in C57Bl/6 mice. Our results show that OX40 engagement led to a significant increase in long-lived antibody responses when compared to mice that did not receive additional co-stimulation. In addition, spike protein and peptide-specific proliferation were greatly increased for both CD4 and CD8 T cells, with augmented secretion of IFN-, TNF- and IL-2. Booster immunizations (7 months post prime) did not lead to anergy, but instead further increased the antibody and T cell responses. In initial experiments, the self-amplifying RNA (saRNA) vaccination generated lower antibody titers, independent of OX40 co-stimulation. However, the saRNA vaccine did induce a robust expansion of spike-specific GrzmB+ CD8 T cells, as revealed by tetramer staining, and these were further increased by OX40 administration. The strong immune responses and the differential effects of the protein and saRNA vaccines suggest that heterologous prime-boost approaches, as currently approved in adults, might be beneficial in boosting different arms of the anti-viral immune response against SARS-CoV-2, with OX40 agonists enhancing both approaches. Further studies in animals will aid defining the effects and benefits of this approach.
Earle A. Chiles Research Institute
Duhen, R; Fox, Bernard A; Weinberg, Andrew D; and See all authors in comments, "OX40 boosts and sustains humoral and cellular immune responses to SARS-CoV-2 spike protein and RNA vaccinations" (2022). Articles, Abstracts, and Reports. 6115.
Duhen R, Beymer M, Jensen SM, Abbina S, Abraham S, Thomas A, Hu HM, Fox BA, Weinberg AD