Distinct regulation of influenza HA head- versus stem-specific B cell responses in HA mRNA-LNP vaccinated and naïve infant African green monkeys.

The generation of memory B cells following influenza virus vaccination and their rapid recruitment into the virus-specific immune response following infection is an essential component of vaccine-induced protection. We have previously reported the capacity of an influenza hemagglutinin (HA) expressing mRNA-LNP vaccine administered to newborn African green monkeys (AGM) to elicit both HA head- and stem-specific antibodies that exhibit a wide array of effector functions. Vaccine-induced responses culminated in enhanced protection compared to non-vaccinated newborn AGM. These results were noteworthy given the lack of an approved influenza vaccine for this age group. Here, we evaluated early antibody and cellular responses following respiratory infection of vaccinated versus naïve animals to gain insights into the events that may be associated with the improved protection in vaccinated newborns. Seven days following challenge, we find an increase in the number of class-switched, affinity matured antibody secreting cells in the lung draining lymph nodes of vaccinated newborns, consistent with recall of memory B cells and rapid differentiation into antibody secreting cells (ASCs). Our data are consistent with a vaccine-mediated affinity advantage in the ASC population. While this benefit extended to HA head-specific germinal center B cells, it was not the case for cells binding HA stem. This was the result of unexpectedly higher apparent affinity of these cells in naïve animals. These data extend our understanding of how vaccination and infection shape activation and differentiation of the head- and stem-specific responses in infants following influenza virus infection.