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

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].

• 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
• Journal: Vaccine (Vaccine) Vol. 38 Issue 6 Pg. 1384-1392 (02 05 2020) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 31843270 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Ltd.

Chemical References

• Antibodies, Bacterial
• Antigens, Bacterial
• Bacterial Outer Membrane Proteins
• Carrier Proteins
• Recombinant Proteins
• Streptococcal Vaccines
• Vaccines, Synthetic
• streptococcal M protein

Topics

• Adult
• Antibodies, Bacterial (immunology)
• Antigens, Bacterial (immunology)
• Bacterial Outer Membrane Proteins (immunology)
• Carrier Proteins (immunology)
• Healthy Volunteers
• Humans
• Immunogenicity, Vaccine
• Recombinant Proteins (immunology)
• Streptococcal Vaccines (adverse effects, immunology)
• Streptococcus pyogenes (immunology)
• Vaccines, Synthetic (adverse effects)