# H1N1 challenge results in rapid recall of stem-specific immunity in HA stem nanoparticle–vaccinated newborn monkeys

## TL;DR

Vaccinating newborn monkeys with an influenza HA stem nanoparticle generates a strong immune memory that quickly responds to infection.

## Contribution

The study demonstrates that vaccination of newborn monkeys with an HA stem nanoparticle induces rapid and cross-reactive immune memory.

## Key findings

- Vaccinated newborn monkeys showed early HA stem IgG+ B cell and antibody-secreting cell responses after infection.
- Vaccination increased HA stem– and head–specific plasma cells, promoting novel antibody responses.
- Antibodies cross-reacting with H5 HA increased, suggesting improved protection against divergent strains.

## Abstract

Primary exposure to influenza antigens during infancy shapes the humoral response to subsequent exposures. Development of a universal vaccine approach to protect newborns against influenza would represent a major step forward. In our previous study, we showed vaccination of newborn African green monkeys (AGMs) with an adjuvanted hemagglutinin (HA) stem nanoparticle induced robust IgG responses with broad recognition across HAs. Here, we examined the cellular responses in the lung-draining lymph node of these vaccinated newborn AGMs following challenge with a heterologous H1N1 virus. Our results show that vaccination is associated with early HA stem IgG+ B cell and antibody-secreting cell responses following infection, consistent with a rapidly recalled memory response. In addition, there was evidence of an increase in both HA stem– and head–specific plasma cells in vaccinated animals, suggesting a vaccine-engendered benefit for novel antibodies targeting HA epitopes. Finally, challenge was associated with preferential increases in antibodies that cross-react with H5 HA, suggesting improved protection against this divergent strain. Overall, these findings indicate that HA stem with AddaVax as adjuvant generates a stem-specific cross-reactive memory pool in newborn AGMs with the potential to be rapidly recalled upon infection.

Universal influenza vaccination in newborn monkeys generates memory responses that are quickly reactivated upon infection and help drive and shape the B cell response