# An intranasal adenoviral-vectored vaccine protects against highly pathogenic avian influenza H5N1 in naive and antigen-experienced animals

## TL;DR

A nasal vaccine using adenovirus protects against deadly bird flu in mice and hamsters, even if they've had flu shots before.

## Contribution

An intranasal adenoviral vaccine provides superior protection against H5N1 compared to intramuscular delivery and works with prior influenza immunity.

## Key findings

- Intranasal ChAd-Texas vaccine elicits mucosal antibody and T cell responses.
- Intranasal delivery protects against H5N1 in mice and hamsters better than intramuscular delivery.
- Prior seasonal flu vaccination does not impair the effectiveness of the ChAd-Texas vaccine.

## Abstract

The emergence of highly pathogenic avian H5N1 influenza viruses in dairy cows and humans has increased the potential for another pandemic. To address this risk, we developed chimpanzee adenoviral (ChAd)-vectored H5 hemagglutinin-targeted vaccines and tested their immunogenicity and efficacy in rodents. Immunization with ChAd-Texas (clade 2.3.4.4b) vaccine in mice elicits neutralizing antibody responses and confers protection against viral infection and mortality upon challenge with a human H5N1 isolate (A/Michigan/90/2024, clade 2.3.4.4b). Intranasal delivery of the ChAd-Texas vaccine elicits mucosal antibody and T cell responses and confers greater protection than intramuscular immunization. In Syrian hamsters, a single intranasal dose of ChAd-Texas vaccine prevents weight loss and reduces airway infection after H5N1 A/Michigan/90/2024 or A/Texas/37/2024 challenge. Importantly, prior seasonal influenza vaccination does not impair antibody responses or protection after intranasal delivery of the ChAd-Texas vaccine. These results support the development of mucosally administered ChAd-Texas HA vaccines as an effective platform for HPAI H5N1 preparedness.

•IN-delivered ChAd-Texas vaccine elicits mucosal antibody and T cell responses•IN-delivered ChAd-Texas vaccine protects against H5N1 in mice and hamsters•IN delivery of ChAd-Texas vaccine confers greater protection than IM delivery•ChAd-Texas induces H5N1 immunity in the setting of prior influenza immunity

IN-delivered ChAd-Texas vaccine elicits mucosal antibody and T cell responses

IN-delivered ChAd-Texas vaccine protects against H5N1 in mice and hamsters

IN delivery of ChAd-Texas vaccine confers greater protection than IM delivery

ChAd-Texas induces H5N1 immunity in the setting of prior influenza immunity

Ying et al. demonstrate that intranasally delivered ChAd-Texas H5 vaccine elicits robust systemic and mucosal immunity that confers protection against homologous H5N1 challenge in rodents. Intranasal immunization outperforms intramuscular delivery and is effective even with pre-existing immunity from seasonal influenza vaccines, highlighting its potential as a vaccine strategy against H5N1.