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Implications for HIV vaccines

Posted by RichardJefferys on 03 Apr 2013 at 14:49 GMT

Kudos to the authors for this novel, fascinating and I think potentially important work. With the caveat that this is a perspective from a non-scientist community-based advocate and writer, I'd like to raise a couple of issues that might be relevant to the implications of the study for HIV vaccines. Firstly, although I cannot claim to fully understand the mathematical model, the paper does not seem to distinguish between naive and memory CD4 T cells, or different subsets of memory CD4 T cells. At least one published study has offered evidence that, after activation, naïve CD4 T cells better support HIV replication than memory CD4 T cells, with the reduced susceptibility of the latter cell type linked to more rapid interferon gamma production[1]. Recently it has been shown that CMV-specific memory CD4 T cells display particularly strong resistance to HIV infection, leading to the recommendation that HIV vaccines should aim to try and induce HIV-specific memory CD4 T cells of a similar phenotype (if possible)[2]. These research findings suggest that induction of relatively resistant HIV-specific memory CD4 T cells by vaccines might be an alternative strategy to using non-HIV antigens. An additional reason for pursuing this strategy is evidence that secondary CD8 T cell responses may also require CD4 T cell help (at least under some conditions)[3], and while the inclusion of non-HIV CD4 T cell antigens would provide help during CD8 T cell priming, it’s not clear to me if they would be able to provide help during a later encounter with HIV (either due to exposure in the case of preventive vaccines, or during ART interruption in the case of therapeutic candidates).

[1] Douek DC, Brenchley JM, Betts MR, et al. HIV preferentially infects HIV-specific CD4+ T cells. Nature. 2002 May 2;417(6884):95-8.
[2] Hu H, Nau M, Ehrenberg P, et al. Distinct gene-expression profiles associated with the susceptibility of pathogen-specific CD4 T cells to HIV-1 infection. Blood. 2013 Feb 14;121(7):1136-44. doi: 10.1182/blood-2012-07-446278.
[3] Novy P, Quigley M, Huang X, Yang Y. CD4 T cells are required for CD8 T cell survival during both primary and memory recall responses. J Immunol. 2007 Dec 15;179(12):8243-51.

No competing interests declared.