Scholars@Duke publication: Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models.

Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models.

Publication , Journal Article

Saunders, KO; Verkoczy, LK; Jiang, C; Zhang, J; Parks, R; Chen, H; Housman, M; Bouton-Verville, H; Shen, X; Trama, AM; Scearce, R; Santra, S ...

Published in: Cell Rep

December 26, 2017

Published version (DOI) Link to item

The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would be critical. Here, we describe the induction of plasma antibodies capable of neutralizing heterologous primary (tier 2) HIV-1 strains in one macaque and two rabbits. Env immunogens were designed to induce CD4 binding site (CD4bs) bnAbs, but surprisingly, the macaque developed V1V2-glycan bnAbs. Env immunization of CD4bs bnAb heavy chain rearrangement (VHDJH) knockin mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs VH chains were replaced with mouse rearrangements bearing diversity region (D)-D fusions, creating antibodies with long, tyrosine-rich HCDR3s. Our results show that Env vaccination can elicit broad neutralization of tier 2 HIV-1, demonstrate that V1V2-glycan bnAbs are more readily induced than CD4bs bnAbs, and define VH replacement and diversity region fusion as potential mechanisms for generating V1V2-glycan bnAb site antibodies.

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 Xiaoying Shen Surgery, Surgical Sciences

Author Georgia Doris Tomaras Surgery, Surgical Sciences

Author Derek Wilson Cain Medicine, Duke Human Vaccine Institute

Author Harold Paul Erickson Cell Biology

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.2017.12.028

EISSN

2211-1247

Publication Date

December 26, 2017

Volume

Issue

Start / End Page

3681 / 3690

Location

United States

Related Subject Headings

env Gene Products, Human Immunodeficiency Virus
Rabbits
Protein Multimerization
Polysaccharides
Mice
Macaca mulatta
Immunization
HIV-1
HIV Antibodies
Epitopes

Citation

APA

Chicago

ICMJE

MLA

NLM

Saunders, K. O., Verkoczy, L. K., Jiang, C., Zhang, J., Parks, R., Chen, H., … Haynes, B. F. (2017). Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models. Cell Rep, 21(13), 3681–3690. https://doi.org/10.1016/j.celrep.2017.12.028

Saunders, Kevin O., Laurent K. Verkoczy, Chuancang Jiang, Jinsong Zhang, Robert Parks, Haiyan Chen, Max Housman, et al. “Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models.” Cell Rep 21, no. 13 (December 26, 2017): 3681–90. https://doi.org/10.1016/j.celrep.2017.12.028.

Saunders KO, Verkoczy LK, Jiang C, Zhang J, Parks R, Chen H, et al. Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models. Cell Rep. 2017 Dec 26;21(13):3681–90.

Saunders, Kevin O., et al. “Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models.” Cell Rep, vol. 21, no. 13, Dec. 2017, pp. 3681–90. Pubmed, doi:10.1016/j.celrep.2017.12.028.

Saunders KO, Verkoczy LK, Jiang C, Zhang J, Parks R, Chen H, Housman M, Bouton-Verville H, Shen X, Trama AM, Scearce R, Sutherland L, Santra S, Newman A, Eaton A, Xu K, Georgiev IS, Joyce MG, Tomaras GD, Bonsignori M, Reed SG, Salazar A, Mascola JR, Moody MA, Cain DW, Centlivre M, Zurawski S, Zurawski G, Erickson HP, Kwong PD, Alam SM, Levy Y, Montefiori DC, Haynes BF. Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models. Cell Rep. 2017 Dec 26;21(13):3681–3690.

Published In

Cell Rep

DOI

10.1016/j.celrep.2017.12.028

EISSN

2211-1247

Publication Date

December 26, 2017

Volume

Issue

Start / End Page

3681 / 3690

Location

United States

Related Subject Headings

env Gene Products, Human Immunodeficiency Virus
Rabbits
Protein Multimerization
Polysaccharides
Mice
Macaca mulatta
Immunization
HIV-1
HIV Antibodies
Epitopes