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Antibodies to the putative SIV infection-enhancing domain diminish beneficial effects of an SIV gp160 vaccine in rhesus macaques.
Mitchell, W M; Torres, J; Johnson, P R; Hirsch, V; Yilma, T; Gardner, M B; Robinson, W E.
Afiliación
  • Mitchell WM; Department of Pathology, Vanderbilt University, Nashville, Tennessee.
AIDS ; 9(1): 27-34, 1995 Jan.
Article en En | MEDLINE | ID: mdl-7893438
OBJECTIVE: To demonstrate that antibodies against amino acids (aa) 603-622 of the SIV gp41 transmembrane glycoprotein enhance infection of SIV in vivo. DESIGN: A synthetic peptide derived from aa 603-622 of SIVmac251 gp41 was synthesized and tested for immunogenicity in rabbits and SIV-infected rhesus macaques. Next, SIV-naive animals were immunized with either a recombinant vaccinia virus expressing the SIV gp160 envelope glycoprotein (VVrgp160) and boosted three times with aa 603-622 (group 1, four animals), wild-type vaccinia virus and boosted with aa 603-622 (group 2, two animals), or VVrgp160 followed by three doses of an irrelevant peptide (group 3, two animals). Animals were challenged with SIVmac251. RESULTS: Peptide aa 603-622 was immunogenic in rabbits. SIV-infected rhesus monkeys immunized with the peptide developed two-three log increases in antibodies to this peptide and antibodies that could enhance SIV infection in vitro. SIV-naive rhesus macaques in group 1 had higher levels of antibody to the peptide by enzyme-linked immunosorbent assay and higher levels of enhancing antibodies at the time of SIV challenge than the animals in groups 2 or 3. Following challenge with SIVmac251 the group 1 animals had detectable p27 antigen longer than animals in group 2 and 3 and died of simian AIDS before the respective animals in the two control groups (P < 0.05 by log-rank test). CONCLUSIONS: aa 603-622 of SIV gp41, like aa 579-613 of HIV gp41, can stimulate production of antibodies that enhance SIV and HIV infection in vitro. Furthermore, immunization with this peptide suppressed beneficial effects of a gp160 vaccine and appeared to enhance SIV infection in vivo.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Productos del Gen env / Proteínas de los Retroviridae / Proteínas del Envoltorio Viral / Síndrome de Inmunodeficiencia Adquirida del Simio / Virus de la Inmunodeficiencia de los Simios / Vacunas contra el SIDAS / Anticuerpos Antivirales Límite: Animals Idioma: En Revista: AIDS Asunto de la revista: SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS) Año: 1995 Tipo del documento: Article Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoproteínas de Membrana / Productos del Gen env / Proteínas de los Retroviridae / Proteínas del Envoltorio Viral / Síndrome de Inmunodeficiencia Adquirida del Simio / Virus de la Inmunodeficiencia de los Simios / Vacunas contra el SIDAS / Anticuerpos Antivirales Límite: Animals Idioma: En Revista: AIDS Asunto de la revista: SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS) Año: 1995 Tipo del documento: Article Pais de publicación: Reino Unido