T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers

Nat Med. 2020 Jun;26(6):932-940. doi: 10.1038/s41591-020-0858-8. Epub 2020 May 11.

Abstract

Recent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induce nAbs, or together with a heterologous viral vector regimen to elicit nAbs and cellular immunity, including CD8+ tissue-resident memory T cells. After ten vaginal challenges with autologous virus, protection was observed in both vaccine groups at 53.3% and 66.7%, respectively. A nAb titer >300 was generally associated with protection but in the heterologous viral vector + nAb group, titers <300 were sufficient. In this group, protection was durable as the animals resisted six more challenges 5 months later. Antigen stimulation of T cells in ex vivo vaginal tissue cultures triggered antiviral responses in myeloid and CD4+ T cells. We propose that cellular immune responses reduce the threshold of nAbs required to confer superior and durable protection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / drug effects*
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / drug effects*
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Gene Products, gag / genetics*
  • Gene Products, gag / immunology
  • Genetic Vectors
  • Immunity, Cellular / drug effects*
  • Immunity, Cellular / immunology
  • Immunity, Heterologous
  • Immunogenicity, Vaccine
  • Immunologic Memory / immunology
  • Macaca mulatta
  • Mucous Membrane
  • SAIDS Vaccines / pharmacology*
  • Simian Acquired Immunodeficiency Syndrome / prevention & control*
  • Simian Immunodeficiency Virus / immunology*
  • Vagina

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Gene Products, gag
  • SAIDS Vaccines