Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys

Abstract

Vaccination with a biologically active Tat protein or tat DNA contained infection with the highly pathogenic SHIV89.6P virus, preventing CD4 T-cell decline and disease onset. Here we show that protection was prolonged, since neither CD4 T-cell decline nor active virus replication was observed in all vaccinated animals that controlled virus replication up to week 104 after the challenge. In contrast, virus persisted and replicated in peripheral blood mononuclear cells and lymph nodes of infected animals, two of which died. Tat-specific antibody, CD4 and CD8 T-cell responses were high and stable only in the animals controlling the infection. In contrast, Gag-specific antibody production and CD4 and CD8 T-cell responses were consistently and persistently positive only in the monkeys that did not control primary virus replication. These results indicate that vaccination with Tat protein or DNA induced long-term memory Tat-specific immune responses and controlled primary infection at its early stages allowing a long-term containment of virus replication and spread in blood and tissues.

HIV Infection «HIV Tat Protein, a Key Factor in Pathogenesis and Immune System Dysregulation: Implication of IL-10»

“…Interestingly several reports showed that humoral or cellular responses against Tat are associated with the control of HIV-1 infection as showed by the low viral load and the protection against AIDS progression (Wieland et al 1990;Krone et al 1988;Reiss 1990;Re 1996;Rezza et al 2005;Zagury et al 1998). In agreement with these observations the group of Ensoli showed that vaccination of macaque with native Tat protein allowed protection against viral infection and disease development (Cafaro et al 1999;Maggiorella et al 2004). However, experiments performed by other groups showed no protection, or only a partial protection in rhesus macaques immunized with native or denatured Tat protein (Allen et al 2002;Silvera et al 2002;Goldstein et al 2000;Pauza et al 2000).…”

Comparative study of Tat vaccine regimens in Mauritian cynomolgus and Indian rhesus macaques: Influence of Mauritian MHC haplotypes on susceptibility/resistance to SHIV89.6P infection

“…Here we addressed these issues, eliminating the latter variables by conducting two identical immunization and challenge protocols in Indian rhesus and Mauritian cynomolgus macaques. The first approach replicated previous studies in cynomolgus macaques in which multiple immunizations with native HIV Tat protein were shown to elicit long-term protection against SHIV 89.6P in Mauritian cynomolgus macaques [26,29]. The second approach was based on a replicationcompetent Ad-recombinant vaccine strategy [30].…”

“…Immunizations of rhesus macaques with Tat protein, vectored tat, Tat toxoid or Tat peptides have elicited no protection [22,23] or partial protection [24,25] against SIV mac239, SHIV 33, or SHIV 89.6P challenges, while immunizations of cynomolgus macaques with native Tat protein or DNA encoding tat have shown strong, long-term protective efficacy against SHIV 89.6P [26][27][28][29].These contrasting results might reflect species differences with regard to immunogenicity or host resistance factors, or differences in vaccine characteristics, vaccination routes, delivery systems, timing of immunizations or challenge protocols. Here we addressed these issues, eliminating the latter variables by conducting two identical immunization and challenge protocols in Indian rhesus and Mauritian cynomolgus macaques.…”

Exploratory clinical studies of a synthetic HIV-1 Tat epitope vaccine in asymptomatic treatment-naïve and antiretroviral-controlled HIV-1 infected subjects plus healthy uninfected subjects

“…19 However, Tat appeared critical to the subsequent development and maintenance of HIV set point viremia following subsistence of activating cytokines. In contrast, recombinant Tat immunization controlled SHIV89.6P infection in cynomologous monkeys, 20 a disparity explained by SHIV89.6P being an acutely pathogenic virus with a disease course dissimilar to HIV. Viral control in this study was associated with T cell immune responses and not with anti-Tat antibody levels.…”