On the basis of epidemiological data demonstrating that the majority of cases of pharyngitis, necrotizing fasciitis, and other invasive streptococcal infections are caused by a limited number of serotypes, this 26-valent vaccine could have significant impact on the overall burden of streptococcal disease.
A multivalent vaccine containing amino-terminal M protein fragments from 26 different serotypes of group A streptococci was constructed by recombinant techniques. The vaccine consisted of four different recombinant proteins that were formulated with alum to contain 400 g of protein per dose. Rabbits were immunized via the intramuscular route at 0, 4, and 16 weeks. Immune sera were assayed for the presence of type-specific antibodies against the individual recombinant M peptides by enzyme-linked immunosorbent assay and for opsonic antibodies by in vitro opsonization tests and indirect bactericidal tests. The 26-valent vaccine was highly immunogenic and elicited fourfold or greater increases in antibody levels against 25 of the 26 serotypes represented in the vaccine. The immune sera were broadly opsonic and were bactericidal against the majority of the 26 different serotypes. Importantly, none of the immune sera cross-reacted with human tissues. Our results indicate that type-specific, protective M protein epitopes can be incorporated into complex, multivalent vaccines designed to elicit broadly protective opsonic antibodies in the absence of tissue-cross-reactive antibodies.Group A streptococcal pharyngitis is one of the most common bacterial infections in school age children. In addition, invasive streptococcal infections afflict thousands of children and adults each year, often resulting in death or significant morbidity (37). Although the incidence of acute rheumatic fever (ARF), a nonsuppurative sequela of streptococcal pharyngitis, has declined in developed countries, the disease is rampant in developing countries (40). Efforts to develop a vaccine that would prevent group A streptococcal infections have been ongoing for more than 8 decades (22,28). New molecular techniques (8) and a better understanding of the biology of group A streptococci (11) have allowed the previous obstacles associated with vaccine development to be overcome.Previous studies have shown that the surface M protein is the major virulence determinant and the major protective antigen of group A streptococci (29). The type specificity of each M protein, of which more than 100 are now known, is largely determined by the epitopes located in the amino-terminal 40 to 50 amino acid residues (3,8,14,27). These regions of M proteins have been shown to evoke antibodies with the greatest bactericidal (protective) activity and are least likely to crossreact with human tissues (2,14,20). Thus, our approach has been to combine small amino-terminal M protein peptides to make multivalent vaccines that would elicit opsonic antibodies against epidemiologically important serotypes of group A streptococci (12,21).In the present study, we constructed a 26-valent M proteinbased vaccine by recombinant technology. The vaccine is composed of four different fusion proteins that contain six or seven M protein fragments linked in tandem. Each component protein of the vaccine was designed to serve as its own carrier, thus obviating the need for unrelated proteins. ...
One influential account asserts that the anterior temporal lobe (ATL) is a domain-general hub for semantic memory. Other evidence indicates it is part of a domain-specific social cognition system. Arbitrating these accounts using functional magnetic resonance imaging has previously been difficult because of magnetic susceptibility artifacts in the region. The present study used parameters optimized for imaging the ATL, and had subjects encode facts about unfamiliar people, buildings, and hammers. Using both conjunction and region of interest analyses, person-selective responses were observed in both the left and right ATL. Neither building-selective, hammer-selective nor domain-general responses were observed in the ATLs, although they were observed in other brain regions. These findings were supported by “resting-state” functional connectivity analyses using independent datasets from the same subjects. Person-selective ATL clusters were functionally connected with the brain's wider social cognition network. Rather than serving as a domain-general semantic hub, the ATLs work in unison with the social cognition system to support learning facts about others.
ROUP A STREPTOCOCCAL INfection and its protean complications continue to cause morbidity and mortality throughout the world. The World Health Organization has estimated that 12 million people have rheumatic heart disease, of whom 400000 die each year. 1 In addition, serious invasive infections, such as bacteremia, streptococcal toxic shock syndrome, and necrotizing fasciitis, plus the more common noninvasive infections, such as pharyngitis and impetigo, produce a significant burden of disease throughout the world. Vaccine prevention of even a fraction of these cases could have a major impact on the health of children and young adults, and potentially reduce the large economic impact of these infections. 2 Efforts to develop a vaccine to prevent group A streptococcal infections have been ongoing for more than 70 years. The surface-expressed M protein is a major protective antigen of group A streptococcus and a frequent
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