Vaccine elicitation of FP-directed antibody that neutralizes up to 59% of HIV

wwwkkk83

Highlights

•

Vaccine elicitation of FP-directed antibody that neutralizes up to 59% of HIV

•

Development for five NHP lineages of vaccine-induced broadly neutralizing antibodies

•

FP-carrier effective at priming and Env-trimer effective at maturing

•

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

Show less

Show footnotes

DOI:https://doi.org/10.1016/j.cell.2019.06.030