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Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease.

Publication ,  Journal Article
Luo, Z; Miranda, HA; Burke, KN; Spurrier, MA; Berry, M; Stover, EL; Spreng, RL; Waitt, G; Soderblom, EJ; Macintyre, AN; Wiehe, K; Heaton, NS
Published in: Sci Transl Med
May 2024

Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of the hemagglutinin (HA) glycoprotein. Because of viral antigenic drift at these sites, vaccines need to be updated and readministered annually. To increase the breadth of influenza vaccine-mediated protection, we developed an antigenically complex mixture of recombinant HAs designed to redirect immune responses to more conserved domains of the protein. Vaccine-induced antibodies were disproportionally redistributed to the more conserved stalk of the HA without hindering, and in some cases improving, antibody responses against the head domain. These improved responses led to increased protection against homologous and heterologous viral challenges in both mice and ferrets compared with conventional vaccine approaches. Thus, antigenically complex protein mixtures can at least partially overcome HA head domain antigenic immunodominance and may represent a step toward a more universal influenza vaccine.

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Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

May 2024

Volume

16

Issue

745

Start / End Page

eadj4685

Location

United States

Related Subject Headings

  • Vaccination
  • Orthomyxoviridae Infections
  • Mice, Inbred BALB C
  • Mice
  • Influenza, Human
  • Influenza Vaccines
  • Humans
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Ferrets
  • Female
 

Citation

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Luo, Z., Miranda, H. A., Burke, K. N., Spurrier, M. A., Berry, M., Stover, E. L., … Heaton, N. S. (2024). Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease. Sci Transl Med, 16(745), eadj4685. https://doi.org/10.1126/scitranslmed.adj4685
Luo, Zhaochen, Hector A. Miranda, Kaitlyn N. Burke, M Ariel Spurrier, Madison Berry, Erica L. Stover, Rachel L. Spreng, et al. “Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease.Sci Transl Med 16, no. 745 (May 2024): eadj4685. https://doi.org/10.1126/scitranslmed.adj4685.
Luo Z, Miranda HA, Burke KN, Spurrier MA, Berry M, Stover EL, et al. Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease. Sci Transl Med. 2024 May;16(745):eadj4685.
Luo, Zhaochen, et al. “Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease.Sci Transl Med, vol. 16, no. 745, May 2024, p. eadj4685. Pubmed, doi:10.1126/scitranslmed.adj4685.
Luo Z, Miranda HA, Burke KN, Spurrier MA, Berry M, Stover EL, Spreng RL, Waitt G, Soderblom EJ, Macintyre AN, Wiehe K, Heaton NS. Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease. Sci Transl Med. 2024 May;16(745):eadj4685.

Published In

Sci Transl Med

DOI

EISSN

1946-6242

Publication Date

May 2024

Volume

16

Issue

745

Start / End Page

eadj4685

Location

United States

Related Subject Headings

  • Vaccination
  • Orthomyxoviridae Infections
  • Mice, Inbred BALB C
  • Mice
  • Influenza, Human
  • Influenza Vaccines
  • Humans
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Ferrets
  • Female