TY - JOUR
T1 - T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers
AU - Arunachalam, Prabhu S.
AU - Charles, Tysheena P.
AU - Joag, Vineet
AU - Bollimpelli, Venkata S.
AU - Scott, Madeleine K.D.
AU - Wimmers, Florian
AU - Burton, Samantha L.
AU - Labranche, Celia C.
AU - Petitdemange, Caroline
AU - Gangadhara, Sailaja
AU - Styles, Tiffany M.
AU - Quarnstrom, Clare F.
AU - Walter, Korey A.
AU - Ketas, Thomas J.
AU - Legere, Traci
AU - Jagadeesh Reddy, Pradeep Babu
AU - Kasturi, Sudhir Pai
AU - Tsai, Anthony
AU - Yeung, Bertrand Z.
AU - Gupta, Shakti
AU - Tomai, Mark
AU - Vasilakos, John
AU - Shaw, George M.
AU - Kang, Chil Yong
AU - Moore, John P.
AU - Subramaniam, Shankar
AU - Khatri, Purvesh
AU - Montefiori, David
AU - Kozlowski, Pamela A.
AU - Derdeyn, Cynthia A.
AU - Hunter, Eric
AU - Masopust, David
AU - Amara, Rama R.
AU - Pulendran, Bali
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41591-020-0858-8
DO - 10.1038/s41591-020-0858-8
M3 - Article
C2 - 32393800
AN - SCOPUS:85082769841
SN - 1078-8956
VL - 26
SP - 932
EP - 940
JO - Nature Medicine
JF - Nature Medicine
IS - 6
ER -