Immune mechanisms and predictors of immune protection and vaccine efficacy 4348

Abstract Description Vaccines have long been pivotal for protection against a host of pathogens, conferring both individual and population-level protection leading to reduced mortality and morbidity across the world. However, vaccine efficacy is highly variable and early predictors of immune response and vaccine-induced memory remain unclear. Here we investigate the early innate-driven mechanisms leading to different grades of induction of adaptive immunity and protection. We vaccinated mice subcutaneously with protective doses of influenza (Sanofi) and SARS-CoV-2 (Pfizer) vaccines and analyzed their immune response in their draining lymph node (inguinal LN) at early time points (6 and 16 hours). When compared to the contralateral LNs, both vaccines led to increased inguinal LN cellularity at rapid times post-vaccination with the influenza vaccine showing earlier peak response at 6 hours compared to SARS-CoV-2 at 16 hours. Moreover, influenza vaccination led to an increase in DCs and B cell numbers, while the SARS-CoV-2 vaccine showed higher numbers of monocytes and NK cells post-vaccination. Preliminary data showed an increase of IFN-induced cytokines (IP-10, MCP-1, MIP-1β, and MIG) at 16 hours post-vaccination in both the serum and draining LN supernatant of SARS-CoV-2-vaccinated mice. Together, these distinct early innate responses induced by vaccination serve as early potential indicators of vaccine efficacy, providing novel correlates of protection for clinical evaluation. Funding Sources DARPA W911NF-23-2-0018 Topic Categories Vaccines and Immunotherapy (VAC)