Vaccine elicitation of FP-directed antibody that neutralizes up to 59% of HIV
Highlights•
Vaccine elicitation of FP-directed antibody that neutralizes up to 59% of HIV
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Development for five NHP lineages of vaccine-induced broadly neutralizing antibodies
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FP-carrier effective at priming and Env-trimer effective at maturing
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Priming with a target subregion induces antibodies with target-interaction hotspots
Summary
The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.
Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization
Rui Kong 14
Hongying Duan 14
Zizhang Sheng 14
Kai Xu 14
Priyamvada Acharya 14
Xuejun Chen 14
Cheng Cheng 14
Adam S. Dingens 14
Jason Gorman 14
Mallika Sastry 14
Chen-Hsiang Shen 14
Baoshan Zhang 14
Tongqing Zhou 14
Gwo-Yu Chuang
Cara W. Chao
Ying Gu
Alexander J. Jafari
Mark K. Louder
Sijy O’Dell
Ariana P. Rowshan
Elise G. Viox
Yiran Wang
Chang W. Choi
Martin M. Corcoran
Angela R. Corrigan
Venkata P. Dandey
Edward T. Eng
Hui Geng
Kathryn E. Foulds
Yicheng Guo
Young D. Kwon
Bob Lin
Kevin Liu
Rosemarie D. Mason
Martha C. Nason
Tiffany Y. Ohr
Li Ou
Reda Rawi
Edward K. Sarfo
Arne Schön
John P. Todd
Shuishu Wang
Hui Wei
Winston Wu
NISC Comparative Sequencing Program11
James C. Mullikin
Robert T. Bailer
Nicole A. Doria-Rose
Gunilla B. Karlsson Hedestam
Diana G. Scorpio
Julie Overbaugh
Jesse D. Bloom
Bridget Carragher
Clinton S. Potter
Lawrence Shapiro
Peter D. Kwong 15
John R. Mascola
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DOI:https://doi.org/10.1016/j.cell.2019.06.030
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