Modulation of vaccine-induced CD4 T cell functional profiles by changes in components of HIV vaccine regimens in humans

Franco Pissani, Bianca Schulte, Michael A. Eller, Bruce T. Schultz, Silvia Ratto-Kim, Mary Marovich, Prasert Thongcharoen, Somchai Sriplienchan, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Stefan Esser, Galit Alter, Merlin L. Robb, Jerome H. Kim, Nelson L. Michael, Hendrik Streeck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


To date, six vaccine strategies have been evaluated in clinical trials for their efficacy at inducing protective immune responses against HIV infection. However, only the ALVAC-HIV/AIDSVAX B/E vaccine (RV144 trial) has demonstrated protection, albeit modestly (31%; P 0.03). One potential correlate of protection was a low-frequency HIV-specific CD4 T cell population with diverse functionality. Although CD4 T cells, particularly T follicular helper (Tfh) cells, are critical for effective antibody responses, most studies involving HIV vaccines have focused on humoral immunity or CD8 T cell effector responses, and little is known about the functionality and frequency of vaccine-induced CD4 T cells. We therefore assessed responses from several phase I/II clinical trials and compared them to responses to natural HIV-1 infection. We found that all vaccines induced a lower magnitude of HIV-specific CD4 T cell responses than that observed for chronic infection. Responses differed in functionality, with a CD40 ligand (CD40L)-dominated response and more Tfh cells after vaccination, whereas chronic HIV infection provoked tumor necrosis factor alpha (TNF-)-dominated responses. The vaccine delivery route further impacted CD4 T cells, showing a stronger Th1 polarization after dendritic cell delivery than after intramuscular vaccination. In prime/boost regimens, the choice of prime and boost influenced the functional profile of CD4 T cells to induce more or less polyfunctionality. In summary, vaccine-induced CD4 T cell responses differ remarkably between vaccination strategies, modes of delivery, and boosts and do not resemble those induced by chronic HIV infection. Understanding the functional profiles of CD4 T cells that best facilitate protective antibody responses will be critical if CD4 T cell responses are to be considered a clinical trial go/no-go criterion.

Original languageEnglish
Article numbere01143
JournalJournal of Virology
Issue number23
StatePublished - 2018
Externally publishedYes


  • CD4 T cells
  • HIV vaccine
  • Human immunodeficiency virus
  • RV144
  • Tfh cells


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