Safety and immunogenicity of a 30-valent M protein-based group a streptococcal vaccine in healthy adult volunteers: A randomized, controlled phase I study

Research output: Contribution to journalArticle

Authors

  • Élodie Pastural
  • Shelly A. McNeil
  • Donna MacKinnon-Cameron
  • Lingyun Ye
  • Joanne M. Langley
  • Robert Stewart
  • Luis H. Martin
  • Gregory J. Hurley
  • Sanaz Salehi
  • Thomas A. Penfound
  • Scott Halperin
  • James B. Dale

External Institution(s)

  • Pan-Provincial Vaccine Enterprise Inc. (PREVENT)
  • Dalhousie University
  • University of Tennessee Health Science Center

Details

Original languageEnglish (US)
Pages (from-to)1384-1392
Number of pages9
JournalVaccine
Volume38
Issue number6
StatusPublished - Feb 5 2020
Peer-reviewedYes

Abstract

Background: Streptococcus pyogenes (group A Streptococcus, Strep A) is a widespread pathogen that continues to pose a significant threat to human health. The development of a Strep A vaccine remains an unmet global health need. One of the major vaccine strategies is the use of M protein, which is a primary virulence determinant and protective antigen. Multivalent recombinant M protein vaccines are being developed with N-terminal M peptides that contain opsonic epitopes but do not contain human tissue cross-reactive epitopes. Methods: We completed a Phase I trial of a recombinant 30-valent M protein-based Strep A vaccine (Strep A vaccine, StreptAnova™) comprised of four recombinant proteins containing N-terminal peptides from 30 M proteins of common pharyngitis and invasive and/or rheumatogenic serotypes, adjuvanted with aluminum hydroxide. The trial was observer-blinded and randomized in a 2:1 ratio for intramuscular administration of Strep A vaccine or an alum-based comparator in healthy adult volunteers, at 0, 30 and 180 days. Primary outcome measures were assessments of safety, including assays for antibodies that cross-reacted with host tissues, and immunogenicity assessed by ELISA with the individual vaccine peptides and by opsonophagocytic killing (OPK) assays in human blood. Results: Twenty-three Strep A-vaccinated participants and 13 controls completed the study. The Strep A vaccine was well-tolerated and there was no clinical evidence of autoimmunity and no laboratory evidence of tissue cross-reactive antibodies. The vaccine was immunogenic and elicited significant increases in geometric mean antibody levels to 24 of the 30 component M antigens by ELISA. Vaccine-induced OPK activity was observed against selected M types of Strep A in vaccinated participants that seroconverted to specific M peptides. Conclusion: The Strep A vaccine was well tolerated and immunogenic in healthy adults, providing strong support for further clinical development. [ClinicalTrials.gov NCT02564237].

    Research areas

  • Bacterial vaccines, Bactericidal activity, Group A Streptococcus, M protein, Multivalent vaccine, Opsonophagocytosis, Phase I clinical trial, Strep A vaccine, StreptAnova™, Streptococcal vaccines, Streptococcus pyogenes

Citation formats

APA

Harvard

Pastural, É, McNeil, SA, MacKinnon-Cameron, D, Ye, L, Langley, JM, Stewart, R, Martin, LH, Hurley, GJ, Salehi, S, Penfound, TA, Halperin, S & Dale, JB 2020, 'Safety and immunogenicity of a 30-valent M protein-based group a streptococcal vaccine in healthy adult volunteers: A randomized, controlled phase I study', Vaccine, vol. 38, no. 6, pp. 1384-1392. https://doi.org/10.1016/j.vaccine.2019.12.005