TY - JOUR
T1 - Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies
AU - Hahn, William O.
AU - Parks, K. Rachael
AU - Shen, Mingchao
AU - Ozorowski, Gabriel
AU - Janes, Holly
AU - Ballweber-Fleming, Lamar
AU - Woodward Davis, Amanda S.
AU - Duplessis, Chris
AU - Tomai, Mark
AU - Dey, Antu K.
AU - Sagawa, Zachary K.
AU - de Rosa, Stephen C.
AU - Seese, Aaron
AU - Kallur Siddaramaiah, Latha
AU - Stamatatos, Leonidas
AU - Lee, Wen-Hsin
AU - Sewall, Leigh M.
AU - Karlinsey, Dalton
AU - Turner, Hannah L.
AU - Rubin, Vanessa
AU - Furth, Sarah
AU - MacPhee, Kellie
AU - Duff, Michael
AU - Corey, Lawrence
AU - Keefer, Michael C.
AU - Edupuganti, Srilatha
AU - Frank, Ian
AU - Maenza, Janine
AU - Baden, Lindsey R.
AU - Hyrien, Ollivier
AU - Sanders, Rogier W.
AU - Moore, John P.
AU - Ward, Andrew B.
AU - Tomaras, Georgia D.
AU - Montefiori, David C.
AU - Rouphael, Nadine
AU - McElrath, M. Juliana
N1 - Publisher Copyright:
© 2024 Hahn et al.
PY - 2024/10/7
Y1 - 2024/10/7
N2 - Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140 formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding, and immunogenicity in a first-in-healthy adult (n = 17), randomized, and placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, and B cell and CD4+ T cell responses emerged after vaccination. Five vaccinees developed serum autologous tier 2 nAbs (ID50 titer, 1:28-1:8647) after two to three doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/Alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes.
AB - Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140 formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding, and immunogenicity in a first-in-healthy adult (n = 17), randomized, and placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, and B cell and CD4+ T cell responses emerged after vaccination. Five vaccinees developed serum autologous tier 2 nAbs (ID50 titer, 1:28-1:8647) after two to three doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/Alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes.
UR - https://www.scopus.com/pages/publications/85203329123
U2 - 10.1084/jem.20240604
DO - 10.1084/jem.20240604
M3 - Article
C2 - 39235529
SN - 0022-1007
VL - 221
JO - Journal of experimental medicine
JF - Journal of experimental medicine
IS - 10
M1 - e20240604
ER -
SDG 3 Good Health and Well-being