Cervico-Vaginal Inflammatory Cytokine and Chemokine Responses to Two Different SIV Immunogens
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Date
2020-08-25
Authors
Toledo, Nikki
Li, Hongzhao
Omange, Were
Dacoba, Tamara
Crecente-Campo, Jose
Schalk, Dane
Kashem, Mohammad
Rakasz, Eva
Schultz-Darken, Nancy
Li, Qingsheng
Journal Title
Journal ISSN
Volume Title
Publisher
Frontiers
Abstract
Studies have shown that vaccine vectors and route of immunization can differentially
activate different arms of the immune system. However, the effects of different HIV
vaccine immunogens on mucosal inflammation have not yet been studied. Because
mucosal sites are the primary route of HIV infection, we evaluated the cervico-vaginal
inflammatory cytokine and chemokine levels of Mauritian cynomolgus macaques
following immunization and boost using two different SIV vaccine immunogens. The
PCS vaccine delivers 12 20-amino acid peptides overlapping the 12 protease cleavage
sites, and the Gag/Env vaccine delivers the full Gag and full Env proteins of simian
immunodeficiency virus. We showed that the PCS vaccine prime and boosts induced
short-lived, lower level increases of a few pro-inflammatory/chemotactic cytokines. In
the PCS-vaccine group only the levels of MCP-1 were significantly increased above the
baseline (P = 0.0078, Week 6; P = 0.0078, Week 17; P = 0.0234; Week 51) following
multiple boosts. In contrast, immunizations with the Gag/Env vaccine persistently
increased the levels of multiple cytokines/chemokines. In the Gag/Env group, higher than
baseline levels were consistently observed for IL-8 (P = 0.0078, Week 16; P = 0.0078,
Week 17; P = 0.0156, Week 52), IL-1b (P = 0.0234, Week 16; P = 0.0156, Week 17;
P = 0.0156, Week 52), and MIP-1a (P = 0.0313, Week 16; P = 0.0156, Week 17;
P = 0.0313, Week 52). Over time, repeated boosts altered the relative levels of these
cytokines between the Gag/Env and PCS vaccine group. 18 weeks after final boost with
a higher dosage, IP-10 levels (P = 0.0313) in the Gag/Env group remained higher than
baseline. Thus, the influence of vaccine immunogens on mucosal inflammation needs to
be considered when developing and evaluating candidate HIV vaccines.
Description
Keywords
HIV, SIV, Vaccine, mucosal inflammation, pro-inflammatory cytokine/chemokine(s), non-human primates
Citation
Toledo NPL, Li H, Omange RW, Dacoba TG, Crecente-Campo J, Schalk D, Kashem MA, Rakasz E, Schultz-Darken N, Li Q, Whitney JB, Alonso MJ, Plummer FA and Luo M (2020) Cervico-Vaginal Inflammatory Cytokine and Chemokine Responses to Two Different SIV Immunogens. Front. Immunol. 11:1935. doi: 10.3389/fimmu.2020.01935