Ragon Faculty Study Identifies Novel Immunization Strategy for Broad Influenza Protection

Date: April 29, 2024 By: Nick Kolev

Researchers at the Ragon Institute have developed a novel immunization strategy that shows promise for protecting against both group 1 and group 2 influenza A viruses. The strategy, detailed in their recent study, relies on eliciting a single amino acid change in antibodies to generate broadly neutralizing antibodies (bnAbs).

Ragon faculty members Daniel Lingwood, PhD, Facundo Batista, PhD, and Aaron Schmidt, PhD, collaborated on the paper published in Immunity this week. Collectively, this study shows that broad influenza immunity can be elicited via an exceptionally simple pathway of human antibody development.

“This highly collaborative project reveals an ‘immunologically special’ and simple molecular switch conferring pan-influenza protection,” said Faez A. Nait Mohamed, PhD, a postdoctoral fellow and one of the authors of the study.

“I am so pleased to be a part of this interdisciplinary production from the Ragon Institute and  our long term collaborators at Scripps,” Batista said.

The study utilized germline-targeting immunogens presented on vaccine nanoparticles to activate bnAb precursors in a humanized mouse model. This method successfully created a type of antibody that can recognize and fight off the influenza virus by targeting a consistent part of the virus known as the hemagglutinin (HA) stem, which is similar in different flu virus groups.

A critical aspect of their finding is the identification of an N55T mutation in the antibody structure. This mutation allows the bnAbs to adapt to variations in the virus’s glycan structures, enhancing their ability to engage with and neutralize the influenza virus. The induced bnAbs underwent a minimal number of mutations, suggesting a direct and efficient pathway from initial activation to mature, effective antibody response.

“I was excited by the opportunity to collaborate with experts in structure and immunogen design on a project that leveraged my own in vivo expertise,” said Rashmi Ray, PhD, a postdoctoral fellow. “Our combined model shows that specific precursor B cells, once activated, undertake a notably quick path to generate cross-reactive Flu antibodies.”

“This work reflects a remarkable level of connectivity and professionalism between the young scientists who conducted the work,” Lingwood said.

This study provides valuable insights into the mechanisms of immune response to influenza and presents a potential pathway for developing universal influenza vaccines. Such vaccines could target common elements of the virus, providing broader protection and reducing the need for frequent reformulation.

This research not only advances our understanding of influenza virus immunology but also highlights the potential of targeted vaccine design in eliciting effective immune responses against diverse influenza strains. The implications for future vaccine development and pandemic preparedness could be significant, offering a foundation for more robust defense mechanisms against evolving viral threats.

More News

Press Releases

New target in sight for HIV vaccine development

Decades into the HIV epidemic, there is as yet no effective vaccine to prevent new cases. In a recent Nature Immunology article (Ray et al.), the Batista lab of the Ragon Institute has preclinically validated a new HIV immunogen design approach from the Scripps Institute’s Schief lab targeting an unexplored site on the HIV-1 Envelope protein (Env).


Alejandro Balazs Receives NIH Avant Garde Award for Innovative HIV and Substance Use Disorder Research

This award is part of the NIH Director’s Pioneer Award mechanism, which supports individual scientists of exceptional creativity who propose high-impact research that will open new areas of HIV research and/or lead to new avenues for prevention and treatment of HIV among people who use drugs.

PRISM 2024 Concludes

Earlier this month, the 2024 Ragon PRISM Science Club concluded after eight weeks of providing high school students from underrepresented communities in the Greater Boston area a hands-on experience of scientific research.