Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239

Abstract

The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated with simian immunodeficiency virus (SIV) gag, tat, rev, and nef using a DNA prime-adenovirus boost strategy. Peak viremia (P ‫؍‬ 0.007) and the chronic phase set point (P ‫؍‬ 0.0192) were significantly decreased in the vaccinated cohort, out to 1 year postinfection. Loss of CD4 ؉ memory populations was also ameliorated in vaccinated animals. Interestingly, only one of the eight vaccinees developed Env-specific neutralizing antibodies after infection. The control observed was significantly improved over that observed in animals vaccinated with SIV gag only. Vaccine-induced cellular immune responses can, therefore, exert a measure of control over replication of the AIDS virus in the complete absence of neutralizing antibody and give us hope that a vaccine designed to induce cellular immune responses might control viral replication.

Simian Immunodeficiency Virus SIVmac239 Infection of Major Histocompatibility Complex-Identical Cynomolgus Macaques from Mauritius

“…The plasma virus concentration was determined using a modification of methods described previously (41). Viral RNA was reverse transcribed and amplified using a SuperScript III Platinum one-step quantitative reverse transcription-PCR system (Invitrogen, Carlsbad, CA) in a LightCycler 1.2 (Roche Diagnostics, Indianapolis, IN).…”

Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian–human immunodeficiency virus viraemia with protein/DNA combination

“…Strategies to improve the efficacy of HIV-1 Env singlecomponent vaccines have been directed at inclusion of gag/ pol structural and/or tat, rev and nef regulatory gene products (Calarota et al, 1998;Hel et al, 2006;Stittelaar et al, 2002;Wilson et al, 2006). Whilst immunization with simian immunodeficiency virus (SIV) Gag, alone or in combination with HIV-1 Env or Nef and Tat, has already yielded promising results, the data must be interpreted with caution as, in most cases, Mamu A*01-positive animals, which mount a particularly robust response to highly conserved Gag peptides, were used (Amara et al, 2001(Amara et al, , 2002Barouch et al, 2001;Casimiro et al, 2005;Egan et al, 2004;Montefiori et al, 1996;Mooij et al, 2004;Seth et al, 2000;Shiver et al, 2002).…”

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

“…Reductions in viral levels and retention of CD4 T cells in macaques challenged with SHIV strains closely related to the vaccine antigens have been reported (3,5,10). Some but not all SIV vaccination studies using similar heterologous prime/boost vaccine modalities have also shown positive results using challenge strains closely matched to vaccine antigens (17,27). Heterologous prime/boost regimens have to date had mixed success in human studies (3,16,17,21).…”