Improving Flu Vaccines With Novel Adjuvants

Technology Overview

Dr. Mridu Acharya

The immune cells known as B cells play a wide range of roles in our bodies. As the production center for antibodies, these cells are foundational to our immune responses that fight off infections. Most vaccines work by prompting our B cells to produce specific antibodies. When this cell activity goes awry, B cells can produce antibodies against our own tissues, which triggers autoimmune disease.

Immunologist Mridu Acharya, PhD, has made discoveries about B cell biology that have important implications for improving influenza vaccine efficacy and potentially developing broader, longer-lasting protection against multiple respiratory viruses. Dr. Acharya and team discovered a B cell protein called the αv integrin (for integrin alpha chain V) that is key in both immunity to infection and autoimmune disease. When this protein is permanently removed in an animal model, increases in self-reactive B cell responses in autoimmunity prone settings can result. But its removal also leads to a much stronger response to the influenza (flu) vaccine.

Compared with control animals, animals with αv integrin removed (“knockout” animals) produced antibodies that react to a broader range of influenza variants, including strains not present in the vaccine. This is a hallmark of a universal flu vaccine, one that would produce lasting immunity against multiple viral variants and might not need to be administered yearly. The Acharya Lab also noticed that the knockout animals exhibited a specific B-cell response in their lungs, the site of influenza infection but where it’s difficult to spur immune responses with traditional flu vaccines. These B-cell responses also had clinical effects: After infection with the influenza virus, integrin-knockout animals survived longer than the control animals and the antibodies produced by the knockout animals showed increased capacity to neutralize viral variants. The findings suggest that targeting the integrin-related pathways could help generate stronger tissue-resident immune responses in the lung and improve protection not only against influenza, but potentially against a broader range of respiratory viral infections.

The αv integrin protein is part of a larger class of integrin proteins, which function in cell adhesion and signaling. Dr. Acharya and collaborators identified novel functions for integrins in antibody-producing B cells. They found that integrins regulate Toll-like receptor (TLR) mediation of B cells as the cells mature, expand and differentiate into long-lived memory cells and plasma cells that generate pathogen-directed antibodies. These memory and plasma cells are the key to long-term vaccine protection.

Current influenza vaccines target only a few of the dozens of influenza strains. Increasing both the magnitude and diversity of antibody responses after vaccination could lead to vaccines that provide broader protection across viral subtypes and could also improve immunity against additional respiratory viruses. To move toward translating her findings for clinical use, Dr. Acharya and team are currently using in vitro and in vivo systems to identify integrin inhibitors that are specific to B cells and reproduce the vaccine-enhancing effects of the integrin knockout. The inhibitors could be used as adjuvants to increase and broaden the response to influenza vaccines.

These adjuvants would not be expected to lead to autoimmune disease because their action in the body is short-lived. In more recent work, the Acharya Lab identified a role for inhibitors of integrins in enhancing expansion of human memory B cells. Current work in the lab is focused on investigating this feature and devising methods to harness integrin inhibition to specifically expand vaccine-induced human memory B cells.

Dr. Acharya’s research focuses on how B cells respond to pathogens while maintaining self-tolerance. In collaboration with pediatric immunologists Richard James, PhD, and David Rawlings, MD, the lab is also developing engineered human B-cell approaches to study and manipulate immune responses in infectious disease and autoimmunity. She is interested in partnerships to develop integrin-targeting compounds as vaccine adjuvants or drugs that modulate B cells to treat autoimmunity. She is also interested in exploring the role of integrins in regulating immune response in the context of other respiratory infectious diseases, including tuberculosis.  

Stage of Development

• Preclinical in vitro
• Preclinical in vivo

Partnering Opportunities

• Collaborative research opportunity
• Sponsored research agreement
• Consultation agreement

Learn More

• Mridu Acharya, PhD
• Acharya Lab

Publications

1. Montiel-Armendariz A, Roe K, Lagos-Orellana J … Acharya M. B cell αv integrin regulates tissue specialization and clonal expansion of lung germinal center and memory B cells after viral infection. Sci Adv. 2026:12(24):eaeb7633.
2. Acharya M, Raso F, Sagadiev S, et al. B cell αv integrins regulate TLR-driven autoimmunity. J Immunol. 2020;205(7):1810-1818.
3. Raso F, Sagadiev S, Du S … Acharya M. αv Integrins regulate germinal center B cell responses through noncanonical autophagy. J Clin Invest. 2018;128(9):4163-4178.
4. Acharya M, Sokolovska A, Tam JM, et al. αv Integrins combine with LC3 and atg5 to regulate Toll-like receptor signalling in B cells. Nat Commun. 2016;7:10917.
5. Edkins AL, Borland G, Acharya M, et al. Differential regulation of monocyte cytokine release by αV and β(2) integrins that bind CD23. Immunol. 2012;136(2):241-251.

Last updated June 11, 2026