Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses

By M. Kanekiyo, M. Joyce, Rebecca A. Gillespie, J. Gallagher, Sarah F. Andrews, Hadi M. Yassine, A. Wheatley, Brian E. Fisher, D. Ambrozak, A. Creanga and 18 more. 2019

271 citations recorded by the source corpus.

The present vaccine against influenza virus has the inevitable risk of antigenic discordance between the vaccine and the circulating strains, which diminishes vaccine efficacy. This necessitates new approaches that provide broader protection against influenza. Here we designed a vaccine using the hypervariable receptor-binding domain (RBD) of viral hemagglutinin displayed on a nanoparticle (np) able to elicit antibody responses that neutralize H1N1 influenza viruses spanning over 90 years. Co-display of RBDs from multiple strains across time, so that the adjacent RBDs are heterotypic, provides an avidity advantage to cross-reactive B cells. Immunization with the mosaic RBD–np elicited broader antibody responses than those induced by an admixture of nanoparticles encompassing the same set of RBDs as separate homotypic arrays. Furthermore, we identified a broadly neutralizing monoclonal antibody in a mouse immunized with mosaic RBD–np. The mosaic antigen array signifies a unique approach that subverts monotypic immunodominance and allows otherwise subdominant cross-reactive B cell responses to emerge. Antigenic variation of influenza A viruses necessitates the annual reformulation of vaccines. Kanekiyo et al. develop a mosaic nanoparticle vaccine against influenza virus that is able to elicit neutralizing antibodies that span nearly 100 years of variation of influenza A virus.

Subfields: Epidemiology, Immunology

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Citations in the corpus

Next-Generation Influenza Vaccines. (2020, background): “This reduces the frequency of responses intolerant to variability and increases the chances for amplifying B cells that tolerate antigenic variation and, hence, subvert the immunodominance (Kanekiyo et al. 2019b).”
Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers (2020, methodology): “For example, the monomeric HA antigens coupled to ferritin were limited to inducing HA head-specific antibodies [16], whereas the trimeric HA ectodomains contained head epitopes as well as stem epitopes that may be partially occluded from interactions with BCRs.”
Title: Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice (2020, unknown): “Here we prepared SpyCatcher003-mi3 nanoparticles (31, 36) simultaneously displaying SpyTagged RBDs from human and animal coronaviruses to evaluate whether mosaic particles can elicit cross-reactive antibody responses, as previously demonstrated for influenza head domain mosaic particles (37).”
Elicitation of broadly protective immunity to influenza by multivalent hemagglutinin nanoparticle vaccines (2020, methodology): “More recently, ferritin was used as a scaffold for co-displaying the monomeric receptor-binding domains (RBDs) from multiple H1 HAs on the same nanoparticle surface 36 .”