Journal Article

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

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

2020

Overview

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. 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. 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. The Strep A vaccine was well tolerated and immunogenic in healthy adults, providing strong support for further clinical development. [ClinicalTrials.gov NCT02564237].

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adult / Adults / Allergy and Immunology / Alum / Aluminum / Aluminum hydroxide / Antibodies / Antibodies, Bacterial - immunology / Antigens / Antigens, Bacterial - immunology / Autoimmunity / Bacterial Outer Membrane Proteins - immunology / Bacterial vaccines / Bactericidal activity / Breastfeeding & lactation / Carrier Proteins - immunology / Enzyme-linked immunosorbent assay / Epitopes / Family medical history / Global health / Group A Streptococcus / Healthy Volunteers / Hematology / Hepatitis / human health / Human tissues / Humans / Immunization / Immunogenicity / Immunogenicity, Vaccine / Infections / intramuscular injection / M protein / Medical laboratories / Multivalent vaccine / Opsonophagocytosis / pathogens / Peptides / Pharyngitis / Phase I clinical trial / Product development / Protective antigen / Proteins / R&D / Randomization / recombinant proteins / Recombinant Proteins - immunology / Research & development / Safety / Serotypes / Strep A vaccine / StreptAnova / Streptococcal vaccines / Streptococcal Vaccines - adverse effects / Streptococcal Vaccines - immunology / Streptococcus / Streptococcus infections / Streptococcus pyogenes / Streptococcus pyogenes - immunology / Syphilis / tissues / Vaccines / Vaccines, Synthetic - adverse effects / Virulence / volunteers