Scholars@Duke publication: Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.

Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.

Publication , Journal Article

Bradley, T; Fera, D; Bhiman, J; Eslamizar, L; Lu, X; Anasti, K; Zhang, R; Sutherland, LL; Scearce, RM; Bowman, CM; Stolarchuk, C; Lloyd, KE ...

Published in: Cell Rep

January 5, 2016

Published version (DOI) Link to item

Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.

Duke Scholars

Author David Charles Montefiori Surgery, Surgical Sciences

Author Michael Anthony Moody Pediatrics, Infectious Diseases

Author Garnett H. Kelsoe Integrative Immunobiology

Author S. Munir Alam Medicine, Duke Human Vaccine Institute

Author Barton Ford Haynes Medicine, Duke Human Vaccine Institute

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Published In

Cell Rep

DOI

10.1016/j.celrep.2015.12.017

EISSN

2211-1247

Publication Date

January 5, 2016

Volume

Issue

Start / End Page

43 / 54

Location

United States

Related Subject Headings

env Gene Products, Human Immunodeficiency Virus
Molecular Sequence Data
Male
Macaca mulatta
Humans
HIV-1
HIV Antibodies
Female
Antibodies, Neutralizing
Animals

Citation

APA

Chicago

ICMJE

MLA

NLM

Bradley, T., Fera, D., Bhiman, J., Eslamizar, L., Lu, X., Anasti, K., … Haynes, B. F. (2016). Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site. Cell Rep, 14(1), 43–54. https://doi.org/10.1016/j.celrep.2015.12.017

Bradley, Todd, Daniela Fera, Jinal Bhiman, Leila Eslamizar, Xiaozhi Lu, Kara Anasti, Ruijung Zhang, et al. “Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.” Cell Rep 14, no. 1 (January 5, 2016): 43–54. https://doi.org/10.1016/j.celrep.2015.12.017.

Bradley T, Fera D, Bhiman J, Eslamizar L, Lu X, Anasti K, et al. Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site. Cell Rep. 2016 Jan 5;14(1):43–54.

Bradley, Todd, et al. “Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.” Cell Rep, vol. 14, no. 1, Jan. 2016, pp. 43–54. Pubmed, doi:10.1016/j.celrep.2015.12.017.

Bradley T, Fera D, Bhiman J, Eslamizar L, Lu X, Anasti K, Zhang R, Sutherland LL, Scearce RM, Bowman CM, Stolarchuk C, Lloyd KE, Parks R, Eaton A, Foulger A, Nie X, Karim SSA, Barnett S, Kelsoe G, Kepler TB, Alam SM, Montefiori DC, Moody MA, Liao H-X, Morris L, Santra S, Harrison SC, Haynes BF. Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site. Cell Rep. 2016 Jan 5;14(1):43–54.

Published In

Cell Rep

DOI

10.1016/j.celrep.2015.12.017

EISSN

2211-1247

Publication Date

January 5, 2016

Volume

Issue

Start / End Page

43 / 54

Location

United States

Related Subject Headings

env Gene Products, Human Immunodeficiency Virus
Molecular Sequence Data
Male
Macaca mulatta
Humans
HIV-1
HIV Antibodies
Female
Antibodies, Neutralizing
Animals