Centers for Disease Control and Prevention. Past Seasons Vaccine Effectiveness Estimates, https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html (2022). Accessed 10 March 2022.

Centers for Disease Control and Prevention. Pandemic influenzapast pandemics, https://www.cdc.gov/flu/pandemic-resources/basics/past-pandemics.html (2022). Accessed 10 March 2022.

Erbelding, E. J. et al. A universal influenza vaccine: the strategic plan for the National Institute of Allergy and Infectious Diseases. J. Infect. Dis. 218, 347354 (2018).

Article CAS PubMed PubMed Central Google Scholar

Giles, B. M. & Ross, T. M. A computationally optimized broadly reactive antigen (COBRA) based H5N1 VLP vaccine elicits broadly reactive antibodies in mice and ferrets. Vaccine 29, 30433054 (2011).

Article CAS PubMed PubMed Central Google Scholar

Giles, B. M., Bissel, S. J., Dealmeida, D. R., Wiley, C. A. & Ross, T. M. Antibody breadth and protective efficacy are increased by vaccination with computationally optimized hemagglutinin but not with polyvalent hemagglutinin-based H5N1 virus-like particle vaccines. Clin. Vaccin. Immunol. 19, 128139 (2012).

Article CAS Google Scholar

Giles, B. M. et al. A computationally optimized hemagglutinin virus-like particle vaccine elicits broadly reactive antibodies that protect nonhuman primates from H5N1 infection. J. Infect. Dis. 205, 15621570 (2012).

Article CAS PubMed PubMed Central Google Scholar

Sautto, G. A. et al. Elicitation of broadly protective antibodies following infection with influenza viruses expressing H1N1 computationally optimized broadly reactive hemagglutinin antigens. Immunohorizons 2, 226237 (2018).

Article CAS PubMed Google Scholar

Sautto, G. A., Ecker, J. W. & Ross, T. M. An H1N1 computationally optimized broadly reactive antigen elicits a neutralizing antibody response against an emerging human-infecting eurasian avian-like swine influenza virus. J. Virol. 95, e0242120 (2021).

Article PubMed Google Scholar

Ross, T. M. et al. A computationally designed H5 antigen shows immunological breadth of coverage and protects against drifting avian strains. Vaccine 37, 23692376 (2019).

Article CAS PubMed Google Scholar

Carter, D. M. et al. Design and characterization of a computationally optimized broadly reactive hemagglutinin vaccine for H1N1 influenza viruses. J. Virol. 90, 47204734 (2016).

Article CAS PubMed PubMed Central Google Scholar

Sautto, G. A. et al. A computationally optimized broadly reactive antigen subtype-specific influenza vaccine strategy elicits unique potent broadly neutralizing antibodies against hemagglutinin. J. Immunol. 204, 375385 (2020).

Article CAS PubMed Google Scholar

Skarlupka, A. L. et al. Computationally optimized broadly reactive vaccine based upon swine H1N1 influenza hemagglutinin sequences protects against both swine and human isolated viruses. Hum. Vaccin Immunother. 15, 20132029 (2019).

Article PubMed PubMed Central Google Scholar

Huang, Y., Owino, S. O., Crevar, C. J., Carter, D. M. & Ross, T. M. N-linked glycans and K147 residue on hemagglutinin synergize to elicit broadly reactive H1N1 influenza virus antibodies. J. Virol. 94, https://doi.org/10.1128/JVI.01432-19 (2020).

Brownlee, G. G. & Fodor, E. The predicted antigenicity of the haemagglutinin of the 1918 Spanish influenza pandemic suggests an avian origin. Philos. Trans. R. Soc. Lond. B Biol. Sci. 356, 18711876 (2001).

Article CAS PubMed PubMed Central Google Scholar

Caton, A. J., Brownlee, G. G., Yewdell, J. W. & Gerhard, W. The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype). Cell 31, 417427 (1982).

Ekiert, D. C. et al. Antibody recognition of a highly conserved influenza virus epitope. Science 324, 246251 (2009).

Article CAS PubMed PubMed Central Google Scholar

Guthmiller, J. J. et al. Broadly neutralizing antibodies target a haemagglutinin anchor epitope. Nature 602, 314320 (2022).

Article CAS PubMed Google Scholar

Sui, J. et al. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat. Struct. Mol. Biol. 16, 265273 (2009).

Article CAS PubMed PubMed Central Google Scholar

Nagashima, K. et al. The pre-existing human antibody repertoire to computationally optimized influenza H1 hemagglutinin vaccines. J. Immunol. 209, 515 (2022).

Article CAS PubMed Google Scholar

Bajic, G. & Harrison, S. C. Antibodies that engage the hemagglutinin receptor-binding site of influenza B viruses. ACS Infect. Dis. 7, 15 (2021).

Article CAS PubMed Google Scholar

Ekiert, D. C. et al. Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature 489, 526532 (2012).

Article CAS PubMed PubMed Central Google Scholar

Guthmiller, J. J. et al. First exposure to the pandemic H1N1 virus induced broadly neutralizing antibodies targeting hemagglutinin head epitopes. Sci. Transl. Med. 13, https://doi.org/10.1126/scitranslmed.abg4535 (2021).

Krause, J. C. et al. A broadly neutralizing human monoclonal antibody that recognizes a conserved, novel epitope on the globular head of the influenza H1N1 virus hemagglutinin. J. Virol. 85, 1090510908 (2011).

Article CAS PubMed PubMed Central Google Scholar

Lee, P. S. et al. Receptor mimicry by antibody F045-092 facilitates universal binding to the H3 subtype of influenza virus. Nat. Commun. 5, 3614 (2014).

Article PubMed Google Scholar

Lee, P. S. et al. Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity. Proc. Natl Acad. Sci. USA 109, 1704017045 (2012).

Article CAS PubMed PubMed Central Google Scholar

McCarthy, K. R. et al. Memory B cells that cross-react with Group 1 and Group 2 Influenza A viruses are abundant in adult human repertoires. Immunity 48, 174184 e179 (2018).

Article CAS PubMed PubMed Central Google Scholar

Schmidt, A. G. et al. Viral receptor-binding site antibodies with diverse germline origins. Cell 161, 10261034 (2015).

Article CAS PubMed PubMed Central Google Scholar

Tsibane, T. et al. Influenza human monoclonal antibody 1F1 interacts with three major antigenic sites and residues mediating human receptor specificity in H1N1 viruses. PLoS Pathog. 8, e1003067 (2012).

Article CAS PubMed PubMed Central Google Scholar

Whittle, J. R. et al. Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Proc. Natl Acad. Sci. USA 108, 1421614221 (2011).

Article CAS PubMed PubMed Central Google Scholar

Winarski, K. L. et al. Vaccine-elicited antibody that neutralizes H5N1 influenza and variants binds the receptor site and polymorphic sites. Proc. Natl Acad. Sci. USA 112, 93469351 (2015).

Article CAS PubMed PubMed Central Google Scholar

Xu, R. et al. A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin. Nat. Struct. Mol. Biol. 20, 363370 (2013).

Article CAS PubMed PubMed Central Google Scholar

Bullard, B. L. & Weaver, E. A. Strategies targeting hemagglutinin as a universal influenza vaccine. Vaccines 9, https://doi.org/10.3390/vaccines9030257 (2021).

Gao, D. et al. Membrane-anchored stalk domain of influenza HA enhanced immune responses in mice. Micro. Pathog. 113, 421426 (2017).

Article CAS Google Scholar

Nachbagauer, R. et al. A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial. Nat. Med. 27, 106114 (2021).

Article CAS PubMed Google Scholar

Nagashima, K. A. & Mousa, J. J. Next-generation influenza HA immunogens and adjuvants in pursuit of a broadly protective vaccine. Viruses 13, https://doi.org/10.3390/v13040546 (2021).

Wohlbold, T. J. et al. Vaccination with soluble headless hemagglutinin protects mice from challenge with divergent influenza viruses. Vaccine 33, 33143321 (2015).

Article CAS PubMed PubMed Central Google Scholar

Eggink, D., Goff, P. H. & Palese, P. Guiding the immune response against influenza virus hemagglutinin toward the conserved stalk domain by hyperglycosylation of the globular head domain. J. Virol. 88, 699704 (2014).

Article PubMed PubMed Central Google Scholar

Lin, S. C., Lin, Y. F., Chong, P. & Wu, S. C. Broader neutralizing antibodies against H5N1 viruses using prime-boost immunization of hyperglycosylated hemagglutinin DNA and virus-like particles. PLoS One 7, e39075 (2012).

Article CAS PubMed PubMed Central Google Scholar

Thornlow, D. N. et al. Altering the immunogenicity of hemagglutinin immunogens by hyperglycosylation and disulfide stabilization. Front Immunol. 12, 737973 (2021).

Article CAS PubMed PubMed Central Google Scholar

Medina, R. A. et al. Glycosylations in the globular head of the hemagglutinin protein modulate the virulence and antigenic properties of the H1N1 influenza viruses. Sci. Transl. Med. 5, 187ra170 (2013).

Article Google Scholar

Nunez, I. A. & Ross, T. M. Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses. Vaccine 38, 830839 (2020).

Article CAS PubMed Google Scholar

Zhang, Y. et al. Influenza research database: an integrated bioinformatics resource for influenza virus research. Nucleic Acids Res. 45, D466D474 (2017).

Article CAS PubMed Google Scholar

Das, S. R. et al. Fitness costs limit influenza A virus hemagglutinin glycosylation as an immune evasion strategy. Proc. Natl Acad. Sci. USA 108, E1417E1422 (2011).

Article CAS PubMed PubMed Central Google Scholar

Wang, C. C. et al. Glycans on influenza hemagglutinin affect receptor binding and immune response. Proc. Natl Acad. Sci. USA 106, 1813718142 (2009).

Article CAS PubMed PubMed Central Google Scholar

Li, T. et al. Identification of a cross-neutralizing antibody that targets the receptor binding site of H1N1 and H5N1 influenza viruses. Nat. Commun. 13, 5182 (2022).

Article CAS PubMed PubMed Central Google Scholar

Ye, J., Ma, N., Madden, T. L. & Ostell, J. M. IgBLAST: an immunoglobulin variable domain sequence analysis tool. Nucleic Acids Res 41, W34W40 (2013).

Article PubMed PubMed Central Google Scholar

Carter, D. M. et al. Elicitation of protective antibodies against a broad panel of H1N1 viruses in ferrets preimmune to historical H1N1 influenza viruses. J. Virol. 91, https://doi.org/10.1128/JVI.01283-17 (2017).

Abbadi, N., Nagashima, K., Pena-Briseno, A., Ross, T. M. & Mousa, J. J. Differential recognition of computationally optimized H3 hemagglutinin influenza vaccine candidates by human antibodies. J. Virol. 96, e0089622 (2022).

Article PubMed Google Scholar

Evans, P. R. & Murshudov, G. N. How good are my data and what is the resolution? Acta Crystallogr. D. Biol. Crystallogr. 69, 12041214 (2013).

Article CAS PubMed PubMed Central Google Scholar

Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D. Biol. Crystallogr. 67, 235242 (2011).

Article CAS PubMed PubMed Central Google Scholar

Winter, G. et al. DIALS: implementation and evaluation of a new integration package. Acta Crystallogr. D. Struct. Biol. 74, 8597 (2018).

Article CAS PubMed PubMed Central Google Scholar

McCoy, A. J. et al. Phaser crystallographic software. J. Appl Crystallogr. 40, 658674 (2007).

Article CAS PubMed PubMed Central Google Scholar

Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D. Biol. Crystallogr. 68, 352367 (2012).

Article CAS PubMed PubMed Central Google Scholar

Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D. Biol. Crystallogr. 66, 486501 (2010).

Article CAS PubMed PubMed Central Google Scholar

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