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

Shelly A. McNeil, Scott A. Halperin, Joanne M. Langley, Bruce Smith, Darlene M. Baxendale, Andrew Warren, Geoffrey P. Sharratt, Mark A. Reddish, Louis F. Fries, Peter E. Vink, James Dale

Research output: Contribution to journalArticle

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Abstract

Background: 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. Methods: 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 AlOH3. 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. Results: 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. Conclusions: The 26-valent GrAS vaccine was well-tolerated and immunogenic in healthy adults; studies in adolescents and children are warranted.

Original languageEnglish (US)
Pages (from-to)303-306
Number of pages4
JournalInternational Congress Series
Volume1289
DOIs
StatePublished - Apr 1 2006

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Streptococcus
Vaccines
Safety
Pharyngitis
Antibodies
Rheumatic Fever
Heart Auscultation
Hepatitis A Vaccines
Necrotizing Fasciitis
Proteins
Septic Shock
North America
Recombinant Proteins
Antibody Formation
Echocardiography
Electrocardiography
Enzyme-Linked Immunosorbent Assay
Injections
Health

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

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

In: International Congress Series, Vol. 1289, 01.04.2006, p. 303-306.

Research output: Contribution to journalArticle

McNeil, SA, Halperin, SA, Langley, JM, Smith, B, Baxendale, DM, Warren, A, Sharratt, GP, Reddish, MA, Fries, LF, Vink, PE & Dale, J 2006, 'A double-blind, randomized phase II trial of the safety and immunogenicity of 26-valent group A streptococcus vaccine in healthy adults', International Congress Series, vol. 1289, pp. 303-306. https://doi.org/10.1016/j.ics.2005.12.002
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. / A double-blind, randomized phase II trial of the safety and immunogenicity of 26-valent group A streptococcus vaccine in healthy adults. In: International Congress Series. 2006 ; Vol. 1289. pp. 303-306.
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AU - McNeil, Shelly A.

AU - Halperin, Scott A.

AU - Langley, Joanne M.

AU - Smith, Bruce

AU - Baxendale, Darlene M.

AU - Warren, Andrew

AU - Sharratt, Geoffrey P.

AU - Reddish, Mark A.

AU - Fries, Louis F.

AU - Vink, Peter E.

AU - Dale, James

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