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Clin. Vaccine Immunol. doi:10.1128/CVI.00030-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Recombinant Group B Streptococcal Alpha-Like Protein 3 is an Effective Immunogen and Carrier Protein

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

^* To whom correspondence should be addressed. Email: lpaoletti{at}channing.harvard.edu.

	Abstract

Conjugate vaccines against pathogens of multiple serotypes are optimized when all components induce functional antibody resulting in broadened coverage. While most clinical studies of vaccines against group B Streptococcus (GBS) have evaluated conjugates composed of capsular polysaccharide (CPS) coupled to tetanus toxoid, conjugates prepared with GBS proteins as carriers have also been efficacious in animals. Here we report that recombinant GBS alpha-like protein 3 (rAlp3) is both a strong immunogen and a viable carrier protein for type III CPS. Type III CPS-specific IgG titer rose from <100 to 64,000 among mice that received type III CPS coupled to rAlp3 compared with an absence of a specific response among mice that received an uncoupled mixture. Most (94%) newborn pups born to III-rAlp-vaccinated dams survived challenge with viable type III GBS compared with 43% survival among those born to dams that received the uncoupled mixture (P <0.0001). A tri-component conjugate of III CPS, rAlp3 and a GBS recombinant beta C protein lacking its IgA binding site (III-rAlp3-rBCP^IgA) provided protection against a serotype III strain and a serotype Ia strain bearing beta C protein. High-titered anti-rAlp3 rabbit serum opsonized Alp3-containing strains of two GBS serotypes (types V and VIII) and invasive type III strains bearing the cross-reactive Rib protein for in vitro killing by human peripheral blood leukocytes. Thus the potential exists for inclusion of rAlp3 in a GBS vaccine formulated to provide multi-serotype coverage.