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

Publication ,  Journal Article
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 ...
Published in: J Clin Invest
March 1, 2019

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-α and IL-6, as well as viral coreceptor agonist MIP1α, 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.

Duke Scholars

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

March 1, 2019

Volume

129

Issue

3

Start / End Page

1314 / 1328

Location

United States

Related Subject Headings

  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • SAIDS Vaccines
  • Rectum
  • Macaca mulatta
  • Intestinal Mucosa
  • Immunology
  • Immunity, Mucosal
  • Immunity, Cellular
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sui, Y., Lewis, G. K., Wang, Y., Berckmueller, K., Frey, B., Dzutsev, A., … Berzofsky, J. A. (2019). Mucosal vaccine efficacy against intrarectal SHIV is independent of anti-Env antibody response. J Clin Invest, 129(3), 1314–1328. https://doi.org/10.1172/JCI122110
Sui, Yongjun, George K. Lewis, Yichuan Wang, Kurt Berckmueller, Blake Frey, Amiran Dzutsev, Diego Vargas-Inchaustegui, et al. “Mucosal vaccine efficacy against intrarectal SHIV is independent of anti-Env antibody response.J Clin Invest 129, no. 3 (March 1, 2019): 1314–28. https://doi.org/10.1172/JCI122110.
Sui Y, Lewis GK, Wang Y, Berckmueller K, Frey B, Dzutsev A, et al. Mucosal vaccine efficacy against intrarectal SHIV is independent of anti-Env antibody response. J Clin Invest. 2019 Mar 1;129(3):1314–28.
Sui, Yongjun, et al. “Mucosal vaccine efficacy against intrarectal SHIV is independent of anti-Env antibody response.J Clin Invest, vol. 129, no. 3, Mar. 2019, pp. 1314–28. Pubmed, doi:10.1172/JCI122110.
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. Mucosal vaccine efficacy against intrarectal SHIV is independent of anti-Env antibody response. J Clin Invest. 2019 Mar 1;129(3):1314–1328.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

March 1, 2019

Volume

129

Issue

3

Start / End Page

1314 / 1328

Location

United States

Related Subject Headings

  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • SAIDS Vaccines
  • Rectum
  • Macaca mulatta
  • Intestinal Mucosa
  • Immunology
  • Immunity, Mucosal
  • Immunity, Cellular