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TitleQuadrivalent influenza nanoparticle vaccines induce broad protection.
Journal, issue, pagesNature, Vol. 592, Issue 7855, Page 623-628, Year 2021
Publish dateMar 24, 2021
AuthorsSeyhan Boyoglu-Barnum / Daniel Ellis / Rebecca A Gillespie / Geoffrey B Hutchinson / Young-Jun Park / Syed M Moin / Oliver J Acton / Rashmi Ravichandran / Mike Murphy / Deleah Pettie / Nick Matheson / Lauren Carter / Adrian Creanga / Michael J Watson / Sally Kephart / Sila Ataca / John R Vaile / George Ueda / Michelle C Crank / Lance Stewart / Kelly K Lee / Miklos Guttman / David Baker / John R Mascola / David Veesler / Barney S Graham / Neil P King / Masaru Kanekiyo /
PubMed AbstractInfluenza vaccines that confer broad and durable protection against diverse viral strains would have a major effect on global health, as they would lessen the need for annual vaccine reformulation ...Influenza vaccines that confer broad and durable protection against diverse viral strains would have a major effect on global health, as they would lessen the need for annual vaccine reformulation and immunization. Here we show that computationally designed, two-component nanoparticle immunogens induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens contain 20 haemagglutinin glycoprotein trimers in an ordered array, and their assembly in vitro enables the precisely controlled co-display of multiple distinct haemagglutinin proteins in defined ratios. Nanoparticle immunogens that co-display the four haemagglutinins of licensed quadrivalent influenza vaccines elicited antibody responses in several animal models against vaccine-matched strains that were equivalent to or better than commercial quadrivalent influenza vaccines, and simultaneously induced broadly protective antibody responses to heterologous viruses by targeting the subdominant yet conserved haemagglutinin stem. The combination of potent receptor-blocking and cross-reactive stem-directed antibodies induced by the nanoparticle immunogens makes them attractive candidates for a supraseasonal influenza vaccine candidate with the potential to replace conventional seasonal vaccines.
External linksNature / PubMed:33762730 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 6.6 Å
Structure data

EMDB-22935:
Elicitation of broadly protective immunity to influenza viruses by multivalent hemagglutinin nanoparticle vaccines
Method: EM (single particle) / Resolution: 6.6 Å

22937

7kna

EMDB-22937, PDB-7kna:
Localized reconstruction of the H1 A/Michigan/45/2015 ectodomain displayed at the surface of I53_dn5 nanoparticle
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-22938:
H5 hemagglutinin ectodomain bound to 1 polyclonal Fab fragment elicited by the qsMosaic-I53_dn5 immunogen
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-22939:
H5 hemagglutinin ectodomain bound to 2 polyclonal Fab fragments elicited by the qsMosaic-I53_dn5 immunogen
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-22940:
H5 hemagglutinin ectodomain bound to 3 polyclonal Fab fragments elicited by the qsMosaic-I53_dn5 immunogen
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • influenza virus
  • influenza a virus
  • synthetic construct (others)
  • unidentified influenza virus
  • Macaca mulatta (Rhesus monkey)
KeywordsVIRAL PROTEIN / hemagglutinin / fusion protein / neutralizing antibodies / vaccine / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID

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