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

Mucosal vaccine efficacy against intrarectal SHIV is independent of anti-Env antibody response. J Clin Invest. 2019 Feb 18;: Authors: Sui Y, Lewis GK, Wang Y, Berckmueller K, Frey B, Dzutsev A, Vargas-Inchaustegui D, Mohanram V, Musich T, Shen X, DeVico A, Fouts T, Venzon D, Kirk J, Waters RC, Talton J, Klinman D, Clements J, Tomaras GD, Franchini G, Robert-Guroff M, Trinchieri G, Gallo RC, Berzofsky JA 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 pop...
Source: Clinical Colorectal Cancer - Category: Cancer & Oncology Authors: Tags: J Clin Invest Source Type: research