# Combination Adjuvants to Program Durable Immunity to Respiratory Viral and Fungal Pathogens

> **NIH NIH U01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $285,674

## Abstract

ABSTRACT: Pre-existing T cell responses have been correlated with decreased disease severity and positive
clinical outcomes during the influenza pandemic of 2009 and the recent COVID-19 pandemic. Therefore,
diversifying T cell responses, particularly targeting conserved internal viral proteins such as the influenza virus
nucleoprotein (NP), could confer protection against both epidemic and pandemic strains of influenza A virus
(IAV). We have designed a mosaic nucleoprotein (MNP) composed of 9-mer epitopes derived from the complete
set of 7,422 NP sequences from human, swine, and avian IAVs. We have strong evidence that a vaccine
formulation consisting of MNP and a combination adjuvant (Adjuplex + TLR-4 agonist glucopyranosyl lipid A
[GLA]) elicits T cell responses that protect against epidemic and pandemic strains of influenza A virus in mice.
Avian influenza viruses have decimated poultry in the US and many parts of the world, and most concerningly,
these viruses have spilled over to infect multiple mammalian species, including cats and cows. Most notably, the
H5N1 avian influenza virus in cows is rapidly spreading to multiple states in the US. Currently, there is serious
concern about the possibility of the rapidly spreading avian influenza virus in cows mutating to gain the potential
to infect humans, cause severe disease, and efficiently spread by airborne transmission. Therefore, it is critical
to develop vaccine strategies to protect humans, and contain avian influenza virus infection and transmission in
cows. Significantly, the MNP we generated exhibits close homology to the NP of the H5N1 virus affecting dairy
cows in the ongoing outbreak. We hypothesize that the MNP will be immunogenic and that T cell responses
elicited by the MNP-based vaccine will provide effective protection against the currently circulating strains of
avian influenza virus isolated from cows.
The aims of this administrative supplement are: (1) Test the hypothesis that mosaic nucleoprotein (MNP)
formulated in the combination adjuvants (Adjuplex+GLA or Adjuplex+CdN) will elicit diverse antibody and T cell
responses in circulation and mammary gland of ferrets and cows; (2) Test the hypothesis that mosaic
nucleoprotein (MNP) formulated in the combination adjuvants (Adjuplex+GLA or Adjuplex+CdN) will protect
ferrets against H5N1 in lungs, upper respiratory tract, and the mammary gland. The proposed studies will have
implications in the development of effective vaccines to protect humans against avian influenza, break the
transmission cycle in cows and mitigate spillover into humans.

## Key facts

- **NIH application ID:** 11133377
- **Project number:** 3U01AI124299-09S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** BRUCE Steven KLEIN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $285,674
- **Award type:** 3
- **Project period:** 2016-02-17 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11133377

## Citation

> US National Institutes of Health, RePORTER application 11133377, Combination Adjuvants to Program Durable Immunity to Respiratory Viral and Fungal Pathogens (3U01AI124299-09S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11133377. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*