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Strong Th1-biased CD4 T cell responses are associated with diminished SIV vaccine efficacy
- Source :
- Sci Transl Med
- Publication Year :
- 2019
-
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.
- Subjects :
- Male
Modified vaccinia Ankara
Receptors, CCR5
Colon
Simian Acquired Immunodeficiency Syndrome
Priming (immunology)
CD8-Positive T-Lymphocytes
medicine.disease_cause
Antibodies, Viral
Article
Interferon-gamma
Immunity
medicine
Cytotoxic T cell
Animals
Lymphocyte Count
HIV vaccine
Mucous Membrane
biology
Gene Expression Profiling
Vaccination
SAIDS Vaccines
General Medicine
T-Lymphocytes, Helper-Inducer
Simian immunodeficiency virus
Virology
Macaca mulatta
Treatment Outcome
Antibody Formation
Vagina
biology.protein
Female
Simian Immunodeficiency Virus
Antibody
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Sci Transl Med
- Accession number :
- edsair.doi.dedup.....138140c4eea73b27c368fc0bd603aef7