Scholars@Duke publication: Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates.

Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates.

Publication , Journal Article

Saunders, KO; Nicely, NI; Wiehe, K; Bonsignori, M; Meyerhoff, RR; Parks, R; Walkowicz, WE; Aussedat, B; Wu, NR; Cai, F; Vohra, Y; Park, PK ...

Published in: Cell Rep

February 28, 2017

Published version (DOI) Link to item

Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans-a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors.

Duke Scholars

Author David Charles Montefiori Surgery, Surgical Sciences

Author Michael Anthony Moody Pediatrics, Infectious Diseases

Author Kevin O'Neil Saunders Surgery, Surgical Sciences

Author Kevin J Wiehe Medicine, Duke Human Vaccine Institute

Author Ryan Meyerhoff

Author Georgia Doris Tomaras Surgery, Surgical Sciences

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.2017.02.003

EISSN

2211-1247

Publication Date

February 28, 2017

Volume

Issue

Start / End Page

2175 / 2188

Location

United States

Related Subject Headings

env Gene Products, Human Immunodeficiency Virus
Vaccines
Primates
Polysaccharides
Mannose
Macaca mulatta
HIV-1
HIV Infections
HIV Antibodies
Epitopes

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APA

Chicago

ICMJE

MLA

NLM

Saunders, K. O., Nicely, N. I., Wiehe, K., Bonsignori, M., Meyerhoff, R. R., Parks, R., … Haynes, B. F. (2017). Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates. Cell Rep, 18(9), 2175–2188. https://doi.org/10.1016/j.celrep.2017.02.003

Saunders, Kevin O., Nathan I. Nicely, Kevin Wiehe, Mattia Bonsignori, R Ryan Meyerhoff, Robert Parks, William E. Walkowicz, et al. “Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates.” Cell Rep 18, no. 9 (February 28, 2017): 2175–88. https://doi.org/10.1016/j.celrep.2017.02.003.

Saunders KO, Nicely NI, Wiehe K, Bonsignori M, Meyerhoff RR, Parks R, et al. Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates. Cell Rep. 2017 Feb 28;18(9):2175–88.

Saunders, Kevin O., et al. “Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates.” Cell Rep, vol. 18, no. 9, Feb. 2017, pp. 2175–88. Pubmed, doi:10.1016/j.celrep.2017.02.003.

Saunders KO, Nicely NI, Wiehe K, Bonsignori M, Meyerhoff RR, Parks R, Walkowicz WE, Aussedat B, Wu NR, Cai F, Vohra Y, Park PK, Eaton A, Go EP, Sutherland LL, Scearce RM, Barouch DH, Zhang R, Von Holle T, Overman RG, Anasti K, Sanders RW, Moody MA, Kepler TB, Korber B, Desaire H, Santra S, Letvin NL, Nabel GJ, Montefiori DC, Tomaras GD, Liao H-X, Alam SM, Danishefsky SJ, Haynes BF. Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates. Cell Rep. 2017 Feb 28;18(9):2175–2188.

Published In

Cell Rep

DOI

10.1016/j.celrep.2017.02.003

EISSN

2211-1247

Publication Date

February 28, 2017

Volume

Issue

Start / End Page

2175 / 2188

Location

United States

Related Subject Headings

env Gene Products, Human Immunodeficiency Virus
Vaccines
Primates
Polysaccharides
Mannose
Macaca mulatta
HIV-1
HIV Infections
HIV Antibodies
Epitopes