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    Mucosal vaccine efficacy against intrarectal SHIV is independent of anti-Env antibody response

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    Author
    Sui, Y.
    Lewis, G.K.
    Wang, Y.
    Date
    2019
    Journal
    The Journal of clinical investigation
    Publisher
    American Society for Clinical Investigation
    Type
    Article
    
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    See at
    https://dx.doi.org/10.1172/JCI122110
    Abstract
    It is widely believed that protection against acquisition of HIV or SIV infection requires anti-envelope (anti-Env) antibodies, and that cellular immunity may affect viral loads but not acquisition, except in special cases. Here we provide evidence to the contrary. Mucosal immunization may enhance HIV vaccine efficacy by eliciting protective responses at portals of exposure. Accordingly, we vaccinated macaques mucosally with HIV/SIV peptides, modified vaccinia Ankara-SIV (MVA-SIV), and HIV-gp120-CD4 fusion protein plus adjuvants, which consistently reduced infection risk against heterologous intrarectal SHIVSF162P4 challenge, both high dose and repeated low dose. Surprisingly, vaccinated animals exhibited no anti-gp120 humoral responses above background and Gag- and Env-specific T cells were induced but failed to correlate with viral acquisition. Instead, vaccine-induced gut microbiome alteration and myeloid cell accumulation in colorectal mucosa correlated with protection. Ex vivo stimulation of the myeloid cell-enriched population with SHIV led to enhanced production of trained immunity markers TNF-? and IL-6, as well as viral coreceptor agonist MIP1?, which correlated with reduced viral Gag expression and in vivo viral acquisition. Overall, our results suggest mechanisms involving trained innate mucosal immunity together with antigen-specific T cells, and also indicate that vaccines can have critical effects on the gut microbiome, which in turn can affect resistance to infection. Strategies to elicit similar responses may be considered for vaccine designs to achieve optimal protective efficacy.
    Keyword
    AIDS vaccine
    Vaccines
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062400881&doi=10.1172%2fJCI122110&partnerID=40&md5=a487b3d0aacf14daacc3aca3c3820bc7; http://hdl.handle.net/10713/8722
    ae974a485f413a2113503eed53cd6c53
    10.1172/JCI122110
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