HIV-1 Vaccination Administered Intramuscularly Can Induce Both Systemic and Mucosal T Cell Immunity in HIV-1-Uninfected Individuals

Abstract

A vaccine regimen that can rapidly control HIV-1 replication at the site of exposure following sexual contact is likely to be the most effective in preventing HIV-1 infection. As part of a larger, phase II clinical trial, we evaluated the ability of a recombinant canarypox HIV-1 vaccine to induce CTL that can be detected in both the systemic and mucosal compartments following i.m. immunization in 12 low- and high-risk HIV-1 seronegative volunteers. In the 7 volunteers receiving four immunizations with live recombinant canarypox ALVAC-HIV vaccine with or without rgp120/SF-2, HIV-1-specific CTL were detected in the blood of 5 (71%) and in the rectum of 4 (57%). CTL responses were observed in both risk strata. In contrast, 5 volunteers receiving placebo had undetectable responses in both compartments. Vaccine-induced, HIV-1-specific effector activities included IFN-γ secretion and class I MHC-restricted CD8+ CTL. Rectal and systemic CD8+ CTL clones established in 1 vaccine recipient revealed similar Env-specific responses and MHC restriction. These findings indicate that parenteral vaccination can induce HIV-1-specific CTL that localize to sites of HIV-1 acquisition, where their presence may be critical in the control of initial viral replication and eventual dissemination. Determination of the optimal strategy to induce mucosal T cells requires future clinical studies.

Gender Differences in Human Immunodeficiency Virus Type 1-Specific CD8 Responses in the Reproductive Tract and Colon following Nasal Peptide Priming and Modified Vaccinia Virus Ankara Boosting

“…MVA alone (15). Our results are in agreement with reports documenting the detection of CD8 ϩ T-cell responses in multiple mucosal sites after induction by systemic immunizations (17,25,33,34,36). However, until the correlates of protective immune responses to HIV-1 challenge are known and the level of those immune responses needed for protection are determined, it will not be conclusively known if a systemic immunization will provide adequate anti-HIV-1 immunity at mucosal sites.…”

Phenotypic and Functional Analysis of Immune CD8+ T Cell Responses Induced by a Single Injection of a HIV DNA Vaccine in Mice

“…Extensive studies have been conducted to develop DNA based vaccines against the devastating human lentivirus HIV-1, the main assay for quantification of induced CMI response being the standard IFN-␥-ELISPOT assay. Even though DNA-vaccinated chimpanzees were protected against HIV-1 challenge (23), DNA vaccines alone, compared with viral vectors, are thought to be relatively weak immunogens in humans (11,24,25). Therefore, with only few exceptions (13,26,27), mainly used anti-HIV DNA vaccine strategies are based on DNA prime or multiprime and boost either with protein or recombinant viruses.…”

Diversity in the Acute CD8 T Cell Response to Vaccinia Virus in Humans

“…The response declines, but persists for several decades in humans, without apparent re-exposure to Ag (10). CD8 responses are also provoked to heterologous Ags inserted into poxviruses (1). Little is known concerning the specificity, diversity, and dynamics of the CD8 response to vaccinia.…”

“…Follow-up vaccinations usually provoke briefer, milder infection, due to pre-existing immunity. Attenuated vaccinia strains such as New York vaccinia (NYVAC) 4 and modified vaccinia Ankara (MVA) that are replication-incompetent in human cells are under study for smallpox prevention, and are also in clinical trials as vector backbones for delivery of heterologous vaccine Ags such as HIV-1, malaria, and tumor Ags (1).…”