Cervicovaginal inflammatory cytokine and chemokine responses to two different SIV vaccines in female mauritian cynomolgus macaques
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Date
2019
Authors
Toledo, Nikki
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Abstract
Human immunodeficiency virus (HIV) -1 infects CD4+ T lymphocytes and activated CD4+ T cells are preferentially targeted. This posed great challenges in developing an effective prophylactic HIV-1 vaccine because candidate HIV vaccine are likely to activate immune system and generate more target cells. Studies have shown that vaccine vectors and route of immunization can differentially activate immune system. The pro-inflammatory and chemotactic cytokines produced by the activated immune cells can propel the cycle of immune activation, target cell recruitment, and enhance infection. However, the effects of vaccine immunogen on immune activation and mucosal inflammation have not been studied. This study aims to evaluate the effect of vaccine immunogen on cervico-vaginal inflammatory cytokine and chemokine levels in Mauritian cynomolgus macaques. Using a customized 14-plex cytokine/chemokine panel, I evaluated the cervico-vaginal cytokine and chemokines during immunization and boosts of two vaccines delivering different immunogens, the PCS vaccine and the Gag/Env vaccine. The PCS vaccine delivers 12 20-amino acid peptides overlapping the 12 simian immunodeficiency virus (SIV) protease cleavage sites (PCS) and the Gag/Env vaccine delivers full Gag and Env proteins. The results show that the PCS vaccine immunization and boosts induced lower level increase of a few pro-inflammatory and chemotactic cytokines, and the effect is short-lived. In contrast, the Gag/Env vaccine induced a persistent increase of multiple cytokines and chemokines with higher magnitude. Thus, it is important to consider the effect of vaccine immunogen on mucosal inflammation when developing and evaluating candidate HIV vaccines.
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Keywords
HIV, Mucosal Inflammation, SIV, Vaccine, NHP