Vaccine Approaches To Protect against Group A Streptococcal Pharyngitis

Vincent A. Fischetti

doi:10.1128/9781555816513.ch10

Chapter 10 : Vaccine Approaches To Protect against Group A Streptococcal Pharyngitis

Author: Vincent A. Fischetti

Content Type: Reference

Publication Year: 2006

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555816513

Chapter DOI: 10.1128/9781555816513.ch10

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Abstract:

Streptococcus pyogenes (Lancefield group A) is a human pathogen responsible for a wide range of diseases, the most common of which are nasopharyngeal infections and impetigo. About 3% of individuals with untreated or inadequately treated streptococcal pharyngitis develop rheumatic fever and rheumatic heart disease, a sequela of the streptococcal infection resulting in cardiac damage, particularly to the mitral valve. This chapter concentrates on the progress to date toward the development of a vaccine to protect against streptococcal nasopharyngeal infection. It was shown more than 50 years ago that the surface M protein would be a prime candidate for a vaccine to protect against streptococcal infection. The chapter describes type-specific protection, multivalent type-specific vaccine, mucosal vaccine for non-type-specific protection, passive protection, active immunization with conserved-region peptides, and the use of gram-positive commensals as vaccine vectors. In addition, it discusses non-M-protein approaches to protect against streptococcal infection. Perhaps a combination vaccine incorporating the serum opsonic power of the polyvalent type-specific approach combined with the mucosal protection offered by a mucosal vaccine will ultimately be the best way to control all pathogenic aspects of a streptococcus.

Citation: Fischetti V. 2006. Vaccine Approaches To Protect against Group A Streptococcal Pharyngitis, p 113-122. In Fischetti V, Novick R, Ferretti J, Portnoy D, Rood J (ed), Gram-Positive Pathogens, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816513.ch10

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Vaccine Approaches To Protect against Group A Streptococcal Pharyngitis

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FIGURE 1

Proposed model of the M protein from M6 strain D471 ( 23a , 29 ). The coiled-coil rod region extends about 60 nm from the cell wall with a short nonhelical domain at the NH2 terminus. The Pro/Gly-rich region of the molecule is found within the peptidoglycan ( 44a ). The membrane-spanning segment is composed of predominantly hydrophobic amino acids, and a short charged tail extends into the cytoplasm. Data suggest that the membrane anchor may be cleaved shortly after synthesis ( 44a ). The A-, B-, and C-repeat regions are indicated along with those segments containing conserved, variable, and hypervariable epitopes among heterologous M serotypes. Pepsin designates the position of a pepsin-susceptible site near the center of the molecule.

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FIGURE 1

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FIGURE 2

The extent of colonization and death of mice challenged with group A streptococci after oral immunization with M-protein conserved-region M6 peptides linked to CTB. Throats of orally immunized mice were swabbed each day after challenge with M14 streptococci, and the specimens were plated on blood plates to determine the extent of colonization compared with that of mice vaccinated with CTB only. Plates showing group A streptococci were scored as positive.

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FIGURE 2

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FIGURE 3

The extent of colonization and death of mice challenged with group A streptococci after oral immunization with recombinant vaccinia virus containing the gene for the whole conserved region of the M6 protein. Throats of orally immunized mice were swabbed each day after challenge with M14 streptococci, and the specimens were plated on blood plates to determine the extent of colonization compared with that of mice vaccinated with wild-type vaccinia only. Plates showing group A streptococci were scored as positive.

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FIGURE 3

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FIGURE 4

M protein-specific salivary IgA in rabbits colonized with S. gordonii expressing the conserved region on the cell surface. Salivary samples were taken after pylocarpine induction and tested in an enzyme-linked immunosorbent assay against the M protein.

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FIGURE 5

M protein-specific serum IgG in rabbits colonized with S. gordonii expressing the conserved region on the cell surface. Blood samples were taken at weekly intervals and tested in ELISA against the M protein.

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