Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection

Sarah Auclair, Fengliang Liu, Qingli Niu, Wei Hou, Gavin Churchyard, Cecilia Morgan, Nicole Frahm, Sorachai Nitayaphan, Punnee Pitisuthithum, Supachai Rerks-Ngarm, Jason T. Kimata, Lynn Soong, Genoveffa Franchini, Merlin Robb, Jerome Kim, Nelson Michael, Haitao Hu

Research output: Contribution to journalArticle

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Abstract

The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination.

Original languageEnglish (US)
Article numbere1006888
JournalPLoS Pathogens
Volume14
Issue number2
DOIs
StatePublished - Feb 1 2018

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AIDS Vaccines
HIV Infections
T-Lymphocytes
Adenoviridae
HIV
Vaccination
Vaccines
Cell Proliferation
CCR5 Receptors
CXCR4 Receptors
Human Adenoviruses
Interleukin-17

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection. / Auclair, Sarah; Liu, Fengliang; Niu, Qingli; Hou, Wei; Churchyard, Gavin; Morgan, Cecilia; Frahm, Nicole; Nitayaphan, Sorachai; Pitisuthithum, Punnee; Rerks-Ngarm, Supachai; Kimata, Jason T.; Soong, Lynn; Franchini, Genoveffa; Robb, Merlin; Kim, Jerome; Michael, Nelson; Hu, Haitao.

In: PLoS Pathogens, Vol. 14, No. 2, e1006888, 01.02.2018.

Research output: Contribution to journalArticle

Auclair, S, Liu, F, Niu, Q, Hou, W, Churchyard, G, Morgan, C, Frahm, N, Nitayaphan, S, Pitisuthithum, P, Rerks-Ngarm, S, Kimata, JT, Soong, L, Franchini, G, Robb, M, Kim, J, Michael, N & Hu, H 2018, 'Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection', PLoS Pathogens, vol. 14, no. 2, e1006888. https://doi.org/10.1371/journal.ppat.1006888
Auclair S, Liu F, Niu Q, Hou W, Churchyard G, Morgan C et al. Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection. PLoS Pathogens. 2018 Feb 1;14(2). e1006888. https://doi.org/10.1371/journal.ppat.1006888
Auclair, Sarah ; Liu, Fengliang ; Niu, Qingli ; Hou, Wei ; Churchyard, Gavin ; Morgan, Cecilia ; Frahm, Nicole ; Nitayaphan, Sorachai ; Pitisuthithum, Punnee ; Rerks-Ngarm, Supachai ; Kimata, Jason T. ; Soong, Lynn ; Franchini, Genoveffa ; Robb, Merlin ; Kim, Jerome ; Michael, Nelson ; Hu, Haitao. / Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection. In: PLoS Pathogens. 2018 ; Vol. 14, No. 2.
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