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

Prabhu S. Arunachalam, Tysheena P. Charles, Vineet Joag, Venkata S. Bollimpelli, Madeleine K.D. Scott, Florian Wimmers, Samantha L. Burton, Celia C. Labranche, Caroline Petitdemange, Sailaja Gangadhara, Tiffany M. Styles, Clare F. Quarnstrom, Korey A. Walter, Thomas J. Ketas, Traci Legere, Pradeep Babu Jagadeesh Reddy, Sudhir Pai Kasturi, Anthony Tsai, Bertrand Z. Yeung, Shakti GuptaMark Tomai, John Vasilakos, George M. Shaw, Chil Yong Kang, John P. Moore, Shankar Subramaniam, Purvesh Khatri, David Montefiori, Pamela A. Kozlowski, Cynthia A. Derdeyn, Eric Hunter, David Masopust, Rama R. Amara, Bali Pulendran

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)932-940
Number of pages9
JournalNature Medicine
Issue number6
StatePublished - Jun 1 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).


  • Animals
  • Antibodies, Neutralizing/drug effects
  • Antibodies, Viral/drug effects
  • CD4-Positive T-Lymphocytes/drug effects
  • CD8-Positive T-Lymphocytes/drug effects
  • Female
  • Gene Products, gag/genetics
  • Genetic Vectors
  • Immunity, Cellular/drug effects
  • 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

PubMed: MeSH publication types

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


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