Engineered immunogen binding to alum adjuvant enhances humoral immunity

Tyson J. Moyer, Yu Kato, Wuhbet Abraham, Jason Y.H. Chang, Daniel W. Kulp, Nicki Watson, Hannah L. Turner, Sergey Menis, Robert K. Abbott, Jinal N. Bhiman, Mariane B. Melo, Hayley A. Simon, Sara Herrera-De la Mata, Shu Liang, Gregory Seumois, Yash Agarwal, Na Li, Dennis R. Burton, Andrew B. Ward, William R. SchiefShane Crotty, Darrell J. Irvine

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Adjuvants are central to the efficacy of subunit vaccines. Aluminum hydroxide (alum) is the most commonly used vaccine adjuvant, yet its adjuvanticity is often weak and mechanisms of triggering antibody responses remain poorly understood. We demonstrate that site-specific modification of immunogens with short peptides composed of repeating phosphoserine (pSer) residues enhances binding to alum and prolongs immunogen bioavailability. The pSer-modified immunogens formulated in alum elicited greatly increased germinal center, antibody, neutralizing antibody, memory and long-lived plasma cell responses compared to conventional alum-adsorbed immunogens. Mechanistically, pSer-immunogen:alum complexes form nanoparticles that traffic to lymph nodes and trigger B cell activation through multivalent and oriented antigen display. Direct uptake of antigen-decorated alum particles by B cells upregulated antigen processing and presentation pathways, further enhancing B cell activation. These data provide insights into mechanisms of action of alum and introduce a readily translatable approach to significantly improve humoral immunity to subunit vaccines using a clinical adjuvant.

Original languageEnglish (US)
Pages (from-to)430-440
Number of pages11
JournalNature Medicine
Volume26
Issue number3
DOIs
StatePublished - Mar 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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