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Circulating memory T follicular helper cells correlate with the development of broadly neutralising antibody responses against HIV

Richard Jefferys, TAG

A study published on 12th September 2013 by the journal Immunity ties together two emerging areas of HIV vaccine research. [1]

In recent years, scientists have discovered that a small proportion of chronically infected individuals develop antibody responses capable of broadly neutralising a diverse array HIV isolates. These antibody responses typically take years to develop, and are not present at sufficient titres to offer noticeable benefit to the infected individuals they are isolated from, but there is reason to believe that if they could be induced by a vaccine they could protect uninfected people against HIV acquisition.

A potential complement to this line of investigation has been the discovery of T follicular helper cells (Tfh), a specialised CD4 T cell subset that plays a critical role in providing help to B cells, thereby facilitating antibody production. Researchers have posited that Tfh may have an important role in the generation of broadly neutralizing antibodies against HIV, but direct evidence has been lacking.

In the Immunity paper, Michela Locci and colleagues report that there is a circulating population of Tfh that can be identified using a combination of surface markers, and that in a large cohort of HIV positive individuals the frequency of these cells correlated with the development of broadly neutralising antibodies against HIV. The data suggest that inducing this type of Tfh response should be a goal for vaccines aiming to create neutralising antibodies against HIV (or potentially any other pathogen).

In a helpful example of kismet, the September 13th issue of the journal Science featured an article by Jon Cohen describing progress in discovering broadly neutralising antibodies to HIV, [2] along with a review on the same topic [3] and a podcast interview with the senior author of the review, Michel Nussenzweig [4].

References:

  1. Locci M et al. Human Circulating PD-1+CXCR3−CXCR5+ Memory Tfh Cells Are Highly Functional and Correlate with Broadly Neutralizing HIV Antibody Responses. Immunity, 12 September 2013 doi:10.1016/j.immuni.2013.08.031.
    http://www.cell.com/immunity/abstract/S1074-7613(13)00383-X
  2. Cohen J. Bound for Glory. Science 13 September 2013: Vol. 341 no. 6151 pp. 1168-1171 DOI: 10.1126/science.341.6151.1168.
    http://www.sciencemag.org/content/341/6151/1168.summary
  3. Klein F et al. Antibodies in HIV-1 vaccine development and therapy. Science 13 September 2013: Vol. 341 no. 6151 pp. 1199-1204 DOI: 10.1126/science.1241144.
    http://www.sciencemag.org/content/341/6151/1199.abstract
  4. Podcast interview with Michel Nussenzweig. Science 13, September 2013, vol. 341 no. 6151 pp. 1199-1204 DOI: 10.1126/science.1241144.
    http://www.sciencemag.org/content/341/6151/1199/suppl/DC1

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