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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

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.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

December 26, 2017

Volume

21

Issue

13

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
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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.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

December 26, 2017

Volume

21

Issue

13

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