Influence of mismatch of env sequences on vaccine protection by live attenuated simian immunodeficiency virus

• Autores: Manrique, Julieta Marina; Piatak, Michael; Lauer, William; Johnson, Welkin; Mansfield, Keith; Lifson, Jeffrey; Desrosier, Ronald
• Año de publicación: 2013
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Vaccine; Simian Immunodeficiency Virus
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Vaccine/challenge experiments that utilize live attenuated strains of simian immunodeficiency virus (SIV) in monkeys may be useful for elucidating what is needed from a vaccine in order to achieve protective immunity. Derivatives of SIVmac239 and SIVmac239Δnef were constructed in which env sequences were replaced with those of the heterologous strain E543; these were then used in vaccine/challenge experiments. When challenge occurred at 22 weeks, 10 of 12 monkeys exhibited apparent sterilizing immunity despite a mismatch of Env sequences, compared to 12 of 12 monkeys with apparent sterilizing immunity when challenge virus was matched in its Env sequence. However, when challenge occurred at 6 weeks, 6 of 6 SIV239Δnef-immunized monkeys became superinfected by challenge virus mismatched in its Env sequence (SIV239/EnvE543). These results contrast markedly not only with the results of the week 22 challenge but also with the sterilizing immunity observed in 5 of 5 SIV239Δnef-immunized rhesus monkeys challenged at 5 weeks with SIV239, i.e., with no mismatch of Env sequences. We conclude from these studies that a mismatch of Env sequences in the challenge virus can have a dramatic effect on the extent of apparent sterilizing immunity when challenge occurs relatively early, 5 to 6 weeks after the nef-deleted SIV administration. However, by 22 weeks, mismatch of Env sequences has little or no influence on the degree of protection against challenge virus. Our findings suggest that anti-Env immune responses are a key component of the protective immunity elicited by live attenuated, nef-deleted SIV.
Fil: Manrique, Julieta Marina. Harvard Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentina
Fil: Piatak, Michael. Frederick National Laboratory. AIDS and Cancer Virus Program; Estados Unidos
Fil: Lauer, William. Harvard Medical School; Estados Unidos
Fil: Johnson, Welkin. Harvard Medical School; Estados Unidos
Fil: Mansfield, Keith. Harvard Medical School; Estados Unidos
Fil: Lifson, Jeffrey. Frederick National Laboratory. AIDS and Cancer Virus Program; Estados Unidos
Fil: Desrosier, Ronald. Harvard Medical School; Estados Unidos