Hypertensive Mice Display Decreased Antibody Responses to COVID-19 Vaccination 2253714

Abstract

Abstract Introduction Hypertensive patients have decreased responses to nearly all COVID vaccines, reflected in increased hospitalization. These studies are largely observational, and the reason why hypertensive patients develop lower antibody responses is not known. We used a mouse model to assess the mechanisms of decreased responses to vaccination during hypertension. We hypothesized that hypertensive mice would show dysregulation of CD4+ T cell populations that may contribute to decreased antibody titers. Methods Hypertension was induced via subcutaneous implantation of osmotic minipumps containing Angiotensin II. One week after induction of hypertension, normotensive and hypertensive mice were vaccinated with two doses (prime-boost twenty-one days apart) of the Pfizer mRNA BNT162b2 vaccine. Two weeks after the boost, serum spike-specific antibody titers and follicular helper T cell numbers in spleens and draining lymph nodes were assessed by CD4+ T cell tetramer staining and flow cytometry. Spike-specific T cell cytokines were also assessed. Results Hypertensive mice showed significantly lower spike-specific and RBD-specific IgG antibody titers than normotensive mice, recapitulating the decreased antibody responses seen in hypertensive humans. Spike-specific antibody titer correlated negatively with systolic blood pressure. Hypertensive mice showed decreased spike-specific CD4+ T cells twenty-one days following prime only and decreased vaccine-specific follicular helper T cells after prime-boost, while spike-specific T cells from normotensive mice produced higher titers of IL-4. Conclusion Our results show dysregulation of vaccine-specific CD4+ T cell numbers and cytokine production during hypertension may be contributing to decreased antibody responses after vaccination. This research will broadly advance our understanding of CD4+ T cells in hypertension and is the first step in creation of vaccines that protect hypertensive patients from greater disease burden of COVID-19. Funding Source R01 AI166756-01A1 and U2C/TL1 Deep South KUH PRIME U2C DK133422 & TL1 DK139566 from the NIH/NIDDK Topic Categories Vaccines and Immunotherapy (VAC)