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Sci Transl Med. 2019 Nov 20;11(519). pii: eaav1800. doi: 10.1126/scitranslmed.aav1800.

Strong TH1-biased CD4 T cell responses are associated with diminished SIV vaccine efficacy.

Author information

1
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
2
Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
3
Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington School of Medicine, Seattle, WA 981909, USA.
4
Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
5
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
6
Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
7
Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA 30322, USA.
8
Department of Pathology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
9
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. ramara@emory.edu.

Abstract

Activated CD4 T cells are a major target of HIV infection. Results from the STEP HIV vaccine trial highlighted a potential role for total activated CD4 T cells in promoting HIV acquisition. However, the influence of vaccine insert-specific CD4 T cell responses on HIV acquisition is not known. Here, using the data obtained from four macaque studies, we show that the DNA prime/modified vaccinia Ankara boost vaccine induced interferon γ (IFNγ+) CD4 T cells [T helper 1 (TH1) cells] rapidly migrate to multiple tissues including colon, cervix, and vaginal mucosa. These mucosal TH1 cells persisted at higher frequencies and expressed higher density of CCR5, a viral coreceptor, compared to cells in blood. After intravaginal or intrarectal simian immunodeficiency virus (SIV)/simian-human immunodeficiency virus (SHIV) challenges, strong vaccine protection was evident only in animals that had lower frequencies of vaccine-specific TH1 cells but not in animals that had higher frequencies of TH1 cells, despite comparable vaccine-induced humoral and CD8 T cell immunity in both groups. An RNA transcriptome signature in blood at 7 days after priming immunization from one study was associated with induction of fewer TH1-type CD4 cells and enhanced protection. These results demonstrate that high and persisting frequencies of HIV vaccine-induced TH1-biased CD4 T cells in the intestinal and genital mucosa can mitigate beneficial effects of protective antibodies and CD8 T cells, highlighting a critical role of priming immunization and vaccine adjuvants in modulating HIV vaccine efficacy.

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