University of Minnesota
https://twin-cities.umn.edu/
612-625-5000
Milestone
2.7.d

Non-HA-based correlates of protection

In progress
High priority

Develop correlates of protection for influenza vaccine candidates based on antigens other than HA (e.g., NA, NP, HA stem), for vaccines produced using novel platforms (e.g., nanoparticles and nucleic acids), and relevant to a variety of endpoints (e.g., cellular immune responses, severe disease).

Progress Highlights

Wagoner 2025 used a systems immunology approach combined with a tonsil organoid model to investigate how host and antigen features affect mucosal and lymphoid tissue responses to influenza vaccines. The study identified immune signatures correlated with nAb responses across seven different influenza vaccines and antigens, including elevated T helper (Th)1 signatures associated with Ab responses to inactivated influenza vaccines.

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Mettelman 2023 evaluated baseline variations in cellular and humoral immune responses among 206 vaccinated or unvaccinated adults in relation to protection from (and increased susceptibility to) symptomatic influenza infection after vaccination. Results showed that protection correlated with diverse and polyfunctional CD4+ and CD8+ T, circulating T follicular helper, T helper type 17, myeloid dendritic and CD16+ natural killer (NK) cell subsets; increased susceptibility correlated with nonspecific inflammatory populations.

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Hoy 2024 used data from two household influenza virus transmission studies across 3 influenza seasons in Nicaragua to identify the HA stem as an independent correlate of protection against H3N2 infection; results also showed that the role of anti-HA stem responses in infection is dependent on age and influenza exposure history.

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