Quadrivalent influenza nanoparticle vaccines induce broad protection

Abstract

Summary paragraph Influenza vaccines that confer broad and durable protection against diverse virus strains would have a major impact on global health 1 . Here we show that computationally designed, two-component nanoparticle immunogens 2 induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens display 20 hemagglutinin (HA) trimers in an ordered array, and their assembly in vitro enables precisely controlled co-display of multiple distinct HAs in defined ratios. Nanoparticle immunogens co-displaying the four HAs of licensed quadrivalent influenza vaccines (QIV) elicited antibody responses against vaccine-matched strains that were equivalent or superior to commercial QIV, and simultaneously induced broadly protective antibody responses to heterologous viruses by targeting the subdominant yet conserved HA stem. The combination of potent receptor-blocking and cross-reactive stem-directed antibodies induced by the nanoparticle immunogens make them attractive candidates for a supraseasonal influenza vaccine candidates with potential to replace conventional seasonal vaccines 3 .

B Cell Responses against Influenza Viruses: Short-Lived Humoral Immunity against a Life-Long Threat

“…Therefore, vaccine strategies that cluster HA on a membrane may ideally stimulate humoral immunity. One strategy to increase BCR crosslinking uses nanoparticles that display diverse HA antigens in which adjacent HAs are heterotypic and antigenically distinct [ 196 , 197 ]. The use of the heterotypic nanoparticles limits the ability of strain-specific B cells to crosslink multiple BCRs across multiple HAs, while conferring an advantage to B cells targeting conserved epitopes that are able to crosslink multiple BCRs across adjacent heterotypic HAs.…”

Animal Models for Influenza Research: Strengths and Weaknesses

“…A study by Darricarrère et al investigated the ability of an HA stembased influenza vaccine to induce broadly cross-reactive neutralizing antibodies against H1 and H3 using an NHP model [158]. The potential effects of quadrivalent influenza nanoparticle vaccines was also investigated in NHPs [159]. Furthermore, Koutsakos et al recently developed flow cytometry-based assays to detect influenza-specific B and T cells in cynomolgus macaques.…”

Animal Models Utilized for the Development of Influenza Virus Vaccines

“…In the 1980s it was discovered that there are two co-circulating IBV lineages [ 21 ]. Another vaccine approach was adopted in the form of a quadrivalent vaccine which is composed of four representative strains, two for IAV and two for IBV [ 22 , 23 , 24 , 25 ].…”

“…They can be designed to express the full-length HA, HA stalk constructs, NA or M2e. The nanoparticles themselves can be quite immunogenetic, however some formulations do contain the adjuvant Matrix-M [ 24 , 47 , 83 , 84 ].…”