Streptococcal Vaccine Candidate

Streptococcal Vaccine Candidate

As early as the 1930s, researchers were pursuing the study of streptococcal vaccinations, with the injection of whole-killed group A streptococci and cell walls thereof culminating in injections of partially purified M protein extracts in the 1970s. However, all interest, especially by the pharmaceutical companies, ceased at that point because the U.S. Food and Drug Administration (FDA) proclaimed that one could work on streptococcal vac-cines as long as no streptococcal component was used! The FDA was afraid that induction of antibodies cross-reactive with human tissues, especially cardiac tis-sues, could be detrimental to the vaccinee. However, it was soon apparent that many individuals had antibodies cross-reactive with a variety of human tissues and were perfectly normal. In the past decade, the restriction was removed on the condition that toxicity studies in animals did not reveal any deletion effects in the animals when injected with a streptococcal vaccine candidate.

This ushered in the search for an effec-tive, safe, and inexpensive group A streptococcal vaccine, and there are now at least four prominent candidates with more in the “pipeline.” This area has recently been reviewed in New Generation Vaccines and will only briefly be sum-marized here.

1.   Perhaps the most advanced candidate is by Dale and colleagues (1996), which is synthetic peptide sequences of a vari-ety of M protein types taken from the variable region of the M protein and hooked together by linkers. This has induced protective immunity in ani-mals to a number of different M protein types and is safe for use in humans. Clinical trial of its efficacy to prevent streptococcal infections is currently under way.

2.   The use of the C-repeat constant region of the M protein advanced by Fischetti (1989) produces protection against oral colonization of the throat by group A streptococci.

 3.   A surface protein called C5 peptidase, which is present on the surface of all group A and group B streptococci, produces antibodies that block both the colonization of group A and group B streptococci in oral colonization studies.

4.   The streptococcal group A carbohydrate (CHO) as proposed by Zabriskie and colleagues has been purified and used as an immunogen to protect against streptococcal infections. This vaccine candidate promotes phagocytosis of group A streptococci of several different M types, will protect against infection using passive and active immunization studies, and also protects against oral colonization. Table 12.1 summarizes all the studies on these four candidates and it can be seen that the variable region of the M protein and the CHO molecule offer the most convincing evidence for a protective vaccine against group A streptococcal infections.