Antibody Repertoires to the Same Ebola Vaccine Antigen Are Differentially Affected by Vaccine Vectors

Michelle Meyer, Asuka Yoshida, Palaniappan Ramanathan, Erica Ollmann Saphire, Peter L. Collins, James E. Crowe, Siba Samal, Alexander Bukreyev

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Comparative immune response profiling is important for selecting next-generation vaccines. We comprehensively evaluated the antibody responses from a panel of nine respiratory vaccines against Ebola virus (EBOV) derived from human and avian paramyxoviruses expressing EBOV glycoprotein (GP). Most vaccines were protective in guinea pigs but yielded antibody repertoires that differed in proportion targeting key antigenic regions, avidity, neutralizing antibody specificities, and linear epitope preferences. Competition studies with monoclonal antibodies from human survivors revealed that some epitopes in GP targeted for neutralization were vector dependent, while EBOV-neutralizing titers correlated with the response magnitude toward the receptor-binding domain and GP1/GP2 interface epitopes. While an immunogen determines the breadth of antibody response, distinct vaccine vectors can induce qualitatively different responses, affecting protective efficacy. These data suggest that immune correlates of vaccine protection cannot be generalized for all vaccines against the same pathogen, even if they use the exact same immunogen. Meyer et al. developed a panel of second-generation Ebola vaccines using respiratory viruses to deliver a common immunogen. The vaccines were protective against lethal infection in guinea pigs. The different vaccines elicited different antibody profiles, indicating correlates of protection may not be universal among Ebola vaccines.

Original languageEnglish (US)
Pages (from-to)1816-1829
Number of pages14
JournalCell Reports
Volume24
Issue number7
DOIs
StatePublished - Aug 14 2018

Keywords

  • Ebola
  • antibody profile
  • immune correlates of protection
  • mucosal
  • respiratory
  • vaccine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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