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.