Immune perturbations in HIV-1-infected individuals who make broadly neutralizing antibodies.
Moody MA., Pedroza-Pacheco I., Vandergrift NA., Chui C., Lloyd KE., Parks R., Soderberg KA., Ogbe AT., Cohen MS., Liao H-X., Gao F., McMichael AJ., Montefiori DC., Verkoczy L., Kelsoe G., Huang J., Shea PR., Connors M., Borrow P., Haynes BF.
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.