Self-Assembling Influenza Nanoparticle Vaccines Elicit Broadly Neutralizing H1N1 Antibodies

By M. Kanekiyo, Chih-Jen Wei, Hadi M. Yassine, P. McTamney, J. Boyington, J. Whittle, S. Rao, W. Kong, Lingshu Wang, G. Nabel. 2013

823 citations recorded by the source corpus.

Influenza viruses pose a significant threat to the public and are a burden on global health systems. Each year, influenza vaccines must be rapidly produced to match circulating viruses, a process constrained by dated technology and vulnerable to unexpected strains emerging from humans and animal reservoirs. Here we use knowledge of protein structure to design self-assembling nanoparticles that elicit broader and more potent immunity than traditional influenza vaccines. The viral haemagglutinin was genetically fused to ferritin, a protein that naturally forms nanoparticles composed of 24 identical polypeptides. Haemagglutinin was inserted at the interface of adjacent subunits so that it spontaneously assembled and generated eight trimeric viral spikes on its surface. Immunization with this influenza nanoparticle vaccine elicited haemagglutination inhibition antibody titres more than tenfold higher than those from the licensed inactivated vaccine. Furthermore, it elicited neutralizing antibodies to two highly conserved vulnerable haemagglutinin structures that are targets of universal vaccines: the stem and the receptor binding site on the head. Antibodies elicited by a 1999 haemagglutinin–nanoparticle vaccine neutralized H1N1 viruses from 1934 to 2007 and protected ferrets from an unmatched 2007 H1N1 virus challenge. This structure-based, self-assembling synthetic nanoparticle vaccine improves the potency and breadth of influenza virus immunity, and it provides a foundation for building broader vaccine protection against emerging influenza viruses and other pathogens.

Subfields: Epidemiology, Immunology

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Citations in the corpus

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “Such nanoparticle vaccines often significantly enhance neutralizing Ab responses compared to traditional subunit vaccines based on non-particulate antigens (Kanekiyo et al., 2015; Kanekiyo et al., 2013; Marcandalli et al., 2019).”
Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus (2019, background): “Second, do anti-scaffold responses detract from or compete with the antigen-specific response? Our data are in accordance with previous studies (Aide et al., 2011; Kanekiyo et al., 2013) in that presentation of DS-Cav1 on the I53-50 nanoparticle induced higher antigen-specific responses despite the ”
Nanoparticle vaccines. (2014, background): “Ferritin is a protein that can self-assemble into nearly-spherical 10 nm structure [126].”
HIV-1 envelope trimer fusion proteins and their applications (2016, positive): “Although the improved immunogenicity was less pronounced in rabbits compared to mice, it is consistent with other observations showing the benefits of particulate antigen presentation [12,17,18] (Fig.”
Vaccine adjuvants: mechanisms and platforms (2023, background): “constructed a nano-influenza vaccine with an antibody titer more than 10 times higher than licensed inactivated vaccines by genetically fusing the hemagglutinin antigen of the H1N1 influenza virus with a ferritin of Helicobacter pylori origin, and inserting the hemagglutinin antigen into the ferriti”
Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles (2016, positive): “We designed two constructs based on the V1V2 of clade-C ZM109: one containing all three disulﬁde bonds (residues 118–206, termed V1V2Ext) and a shortened version containing only two (residues 125–197, termed V1V2Sht), each fused to the N terminus (D5) of FR subunit 32,35 (Fig.”
Development of a Pan-H1 Influenza Vaccine (2018, methodology): “HA (11), EBV gp220 (25), and HIV envelope (26).”
Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site (2015, methodology): “Recent advances in nanoparticle technology further accentuate the benefits of symmetrically arrayed antigens to activate B cells through low-affinity BCRs (Jardine et al., 2013; Lingwood et al., 2012) and improve vaccine-induced immunity (Kanekiyo et al., 2013).”
Self-assembling protein nanoparticles in the design of vaccines (2015, neutral): “For some chimeric nanoparticles, there is evidence that the immunogenicity of the platform carrier itself is negligible or low compared to that of the mounted immunogen being presented [93].”
New Vaccine Design and Delivery Technologies (2019, background): “The discovery that nonviral self-assembling proteins such as ferritin and lumazine synthase can form monodisperse immunogens that present large, complex antigens has recently moved the field beyond this limitation [24, 69] .”
Next-Generation Influenza Vaccines. (2020, background): “Recombinant HA and/or NA proteins derived from pandemic strain sequences could also be produced in insect or mammalian cells either as soluble proteins or displayed on nanoparticles (Kanekiyo et al. 2013; Georgiev et al. 2018; Marcandalli et al. 2019).”
Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers (2018, background): “To assess the generality of this concept, we assessed trafficking of another highly glycosylated nanoparticle immunogen, influenza hemagluttinin (HA)-ferritin 8-mer particles (4), which were also targeted to the FDC network in wild type but not MBL KO mice (fig.”