HIV vaccines – bad news, good news
It’s been a bad week for HIV vaccines, with the announcement that the Merck phase II STEP vaccine trial involving 3,000 volunteers was halted because the vaccine did not block HIV infection. This international trial was regarded as “test of concept” of the vaccine – which included three recombinant HIV genes delivered by a weakened adenovirus vector – in uninfected volunteers at high risk for acquiring HIV infection, mainly homosexual men, but including some women in North and South America, the Caribbean, and Australia. Among the 741 volunteers who got at least one of the three planned doses of vaccine, there were 24 cases of HIV infection, compared with 21 infections among the 762 participants who received a placebo.
Related: Adenovirus vectors – new genes, new vaccines
Clearly, there’s still a long road to tread until we have an effective HIV vaccine, and the only way we’re going to get there is not by trial and error but through a much better understanding of what is involved in immune protection against HIV infection. For that reason, a recent paper looking at immunity to HIV-2 infection is of interest:
HIV-2 infection in the majority of infected subjects follows an attenuated disease course that distinguishes it from infection with HIV-1. Antigen-specific T cells are pivotal in the management of chronic viral infections but are not sufficient to control viral replication in HIV-1–positive subjects, and their function in HIV-2 infection is not fully established. In a community-based cohort of HIV-2 long-term non-progressors in rural Guinea-Bissau, the authors performed what they believe is the first comprehensive analysis of HIV-2–specific immune responses. This demonstrated that Gag is the most immunogenic protein in HIV-2. The magnitude of the IFN-gamma immune response to the HIV-2 proteome was inversely correlated with HIV-2 viraemia, and this relationship was specifically due to the targeting of Gag. Furthermore, patients with undetectable viraemia had greater Gag-specific responses compared with patients with high viral replication. The most frequently recognized peptides clustered within a defined region of Gag, and responses to a single peptide in this region were associated with low viral burden. The consistent relationship between Gag-specific immune responses and viraemia control suggests that T cell responses are vital in determining the superior outcome of HIV-2 infection. A better understanding of how HIV-2 infection is controlled may identify correlates of effective protective immunity essential for the design of HIV vaccines.
Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection.
J Clin Invest. 2007 Sep 6
Tags: adenovirus, genes, HIV, infection, placebo, recombinant, T cells, trial, vaccine, vector, volunteers
[...] HIV vaccines – bad news, good news [...]
Interestingly, there is pretty good evidence that control of HIV viral load in infected people is correlated with a strong anti-Gag CD8+ T-cell response – and negatively correlated with an anti-Env (gp120/gp41) response.
So how do you elicit strong anti-Gag responses in CD8+ cells – generally regarded as cytotoxic T-cells (CTL) – without provoking responses in CD4+ cells, which proliferate and then raise teh chance of getting infected with HIV?
Carefully, carefully…Gag-only vaccines, possibly; adjuvants which selectively stimulate CD8+ responses…who knows??
[...] HIV vaccines – bad news, good news [...]
[...] HIV vaccines – bad news, good news [...]