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Shelly A McNeil,
Scott A Halperin,
Joanne M Langley,
Bruce Smith,
Andrew Warren, Geoffrey P Sharratt,
Darlene M Baxendale,
Mark A Reddish,
Mary C Hu,
Steven D Stroop,
Janine Linden,
Louis F Fries,
Peter E Vink,
James B Dale
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ABSTRACT: Group A streptococcus (GAS) 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 the previous obstacles to be largely overcome.
The vaccine is comprised of 4 recombinant proteins adsorbed to aluminum hydroxide that contain N-terminal peptides from streptococcal protective antigen and M proteins of 26 common pharyngitis, invasive, and/or rheumatogenic serotypes. Thirty healthy adult subjects received intramuscular 26-valent GAS vaccine (400 microg) at 0, 1, and 4 months, with clinical and laboratory follow-up for safety and immunogenicity using assays for tissue cross-reactive antibodies, type-specific M antibodies to 27 vaccine antigens, and functional (opsonization) activity of M protein antibodies.
The incidence of local reactogenicity was similar to that for other aluminum hydroxide-adsorbed vaccines in adults. No subject developed evidence of rheumatogenicity or nephritogenicity, and no induction of human tissue-reactive antibodies was detected. Overall, 26 of 27 antigenic peptides evoked a >4-fold increase in the geometric mean antibody titer over baseline. The mean log2 fold-increase in serum antibody titer (+/- standard error of the mean) for all 27 antigens was 3.67 +/- 0.21. A significant mean log2 reduction in streptococcal bacterial counts in serum samples obtained after immunization was seen in opsonization assays for all M serotypes.
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.
Clinical Infectious Diseases 11/2005; 41(8):1114-22. · 9.15 Impact Factor
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ABSTRACT: We report a case of a true cleft in the anterior leaflet of the mitral valve. The cleft, however, is directed toward the ventricular septum, and the left ventricular papillary muscles have the same arrangement as seen in the setting of a common atrioventricular orifice. The atrioventricular septum is intact. This appearance reflects the presence, in this patient, of right ventricular origin of a solitary arterial trunk, so that there was no outflow tract within the left ventricle to interpose between the mitral valve and the septum.
Cardiology in the Young 09/2004; 14(4):444-6. · 0.76 Impact Factor
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Geoffrey P. Sharratt
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ABSTRACT: We report a case of a true cleft in the anterior leaflet of the mitral valve. The cleft, however, is directed toward the ventricular septum, and the left ventricular papillary muscles have the same arrangement as seen in the setting of a common atrioventricular orifice. The atrioventricular septum is intact. This appearance reflects the presence, in this patient, of right ventricular origin of a solitary arterial trunk, so that there was no outflow tract within the left ventricle to interpose between the mitral valve and the septum.
Cardiology in the Young 07/2004; 14(04):444 - 446. · 0.76 Impact Factor
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Cardiology in the Young 05/2003; 13(2):184-90. · 0.76 Impact Factor
