A double-blind, randomized phase II trial of the safety and immunogenicity of 26-valent group A streptococcus vaccine in healthy adults

• Published in: International Congress series Vol. 1289; pp. 303 - 306
• Main Authors: McNeil, Shelly A., Halperin, Scott A., Langley, Joanne M., Smith, Bruce, Baxendale, Darlene M., Warren, Andrew, Sharratt, Geoffrey P., Reddish, Mark A., Fries, Louis F., Vink, Peter E., Dale, James B.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.04.2006
• Subjects: Bacterial vaccine; Streptococcal M protein; Streptococcus pyogenes; Streptococcal M protein; Streptococcus pyogenes; Bacterial vaccine
• ISSN: 0531-5131; 1873-6157
• DOI: 10.1016/j.ics.2005.12.002

GrAS causes illness ranging from uncomplicated pharyngitis to life-threatening necrotizing fasciitis, toxic shock and rheumatic fever. Attempts to develop an M protein-based vaccine have been hindered by the fact that some M proteins elicit both protective antibodies and antibodies that cross-react with human tissues. New molecular techniques have allowed this obstacle to be largely overcome. We performed a phase II trial of a 26-valent GrAS vaccine comprising four recombinant proteins containing N-terminal peptides from 26 M proteins (plus Spa = 27) of common pharyngitis, invasive, and/or rheumatogenic serotypes adsorbed to AlOH 3. Subjects were screened for good health and underwent baseline cardiac auscultation, echocardiography, ECG, and screening for human tissue-cross-reacting antibodies. Subjects (mean age = 33.6, range 18.9–50.9) were randomized in a 70:20 ratio to receive either GrAS or control vaccine, Havrix™, intramuscularly at 0, 1 and 6 months, with clinical and laboratory follow-up for safety and assay of type-specific M antibodies by quantitative ELISA. No vaccine-associated serious adverse events (SAE) occurred. Most adverse events (AEs) were at the injection site and were mild and self-limited. Systemic AEs were uncommon and did not differ between the 2 groups. No subject developed clinical or laboratory evidence of rheumatogenicity or nephritogenicity, and no induction of human tissue-reactive antibodies was demonstrated. The vaccine was highly immunogenic, eliciting an antibody response to the majority of group A streptococcus serotypes associated with pharyngitis, acute rheumatic fever, and invasive disease in North America The 26-valent GrAS vaccine was well-tolerated and immunogenic in healthy adults; studies in adolescents and children are warranted.