Research ArticleHIV

Immune perturbations in HIV-1–infected individuals who make broadly neutralizing antibodies

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Science Immunology  29 Jul 2016:
Vol. 1, Issue 1, pp. aag0851
DOI: 10.1126/sciimmunol.aag0851

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Setting the stage for HIV vaccines

Some HIV-infected individuals produce antibodies that can target multiple HIV strains—broadly neutralizing antibodies. Moody et al. now compare HIV-infected individuals who produce these antibodies with those who do not. They find that broadly neutralizing antibody production associates with particular immune traits, including a higher frequency of autoantibodies, fewer regulatory T cells, and more circulating memory T follicular helper cells. Vaccine protocols that can mimic these immune perturbations may therefore promote induction of broadly neutralizing antibodies and lead to a more successful immune response to HIV.


Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. bnAbs occur in some HIV-1–infected individuals and frequently have characteristics of autoantibodies. We have studied cohorts of HIV-1–infected individuals who made bnAbs and compared them with those who did not do so, and determined immune traits associated with the ability to produce bnAbs. HIV-1–infected individuals with bnAbs had a higher frequency of blood autoantibodies, a lower frequency of regulatory CD4+ T cells, a higher frequency of circulating memory T follicular helper CD4+ cells, and a higher T regulatory cell level of programmed cell death–1 expression compared with HIV-1–infected individuals without bnAbs. Thus, induction of HIV-1 bnAbs may require vaccination regimens that transiently mimic immunologic perturbations in HIV-1–infected individuals.

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