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Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens.

Publication ,  Journal Article
Hessell, AJ; Malherbe, DC; Pissani, F; McBurney, S; Krebs, SJ; Gomes, M; Pandey, S; Sutton, WF; Burwitz, BJ; Gray, M; Robins, H; Park, BS ...
Published in: J Immunol
April 1, 2016

Advancement in immunogen selection and vaccine design that will rapidly elicit a protective Ab response is considered critical for HIV vaccine protective efficacy. Vaccine-elicited Ab responses must therefore have the capacity to prevent infection by neutralization-resistant phenotypes of transmitted/founder (T/F) viruses that establish infection in humans. Most vaccine candidates to date have been ineffective at generating Abs that neutralize T/F or early variants. In this study, we report that coimmunizing rhesus macaques with HIV-1 gp160 DNA and gp140 trimeric protein selected from native envelope gene sequences (envs) induced neutralizing Abs against Tier 2 autologous viruses expressing cognate envelope (Env). The Env immunogens were selected from envs emerging during the earliest stages of neutralization breadth developing within the first 2 years of infection in two clade B-infected human subjects. Moreover, the IgG responses in macaques emulated the targeting to specific regions of Env known to be associated with autologous and heterologous neutralizing Abs developed within the human subjects. Furthermore, we measured increasing affinity of macaque polyclonal IgG responses over the course of the immunization regimen that correlated with Tier 1 neutralization. In addition, we report firm correlations between Tier 2 autologous neutralization and Tier 1 heterologous neutralization, as well as overall TZM-bl breadth scores. Additionally, the activation of Env-specific follicular helper CD4 T cells in lymphocytes isolated from inguinal lymph nodes of vaccinated macaques correlated with Tier 2 autologous neutralization. These results demonstrate the potential for native Env derived from subjects at the time of neutralization broadening as effective HIV vaccine elements.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

April 1, 2016

Volume

196

Issue

7

Start / End Page

3064 / 3078

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccination
  • T-Lymphocyte Subsets
  • Neutralization Tests
  • Macaca mulatta
  • Lymphoid Tissue
  • Immunology
  • Immunoglobulin G
  • Immunization Schedule
  • Immunization
 

Citation

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Hessell, A. J., Malherbe, D. C., Pissani, F., McBurney, S., Krebs, S. J., Gomes, M., … Haigwood, N. L. (2016). Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens. J Immunol, 196(7), 3064–3078. https://doi.org/10.4049/jimmunol.1500527
Hessell, Ann J., Delphine C. Malherbe, Franco Pissani, Sean McBurney, Shelly J. Krebs, Michelle Gomes, Shilpi Pandey, et al. “Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens.J Immunol 196, no. 7 (April 1, 2016): 3064–78. https://doi.org/10.4049/jimmunol.1500527.
Hessell AJ, Malherbe DC, Pissani F, McBurney S, Krebs SJ, Gomes M, et al. Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens. J Immunol. 2016 Apr 1;196(7):3064–78.
Hessell, Ann J., et al. “Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens.J Immunol, vol. 196, no. 7, Apr. 2016, pp. 3064–78. Pubmed, doi:10.4049/jimmunol.1500527.
Hessell AJ, Malherbe DC, Pissani F, McBurney S, Krebs SJ, Gomes M, Pandey S, Sutton WF, Burwitz BJ, Gray M, Robins H, Park BS, Sacha JB, LaBranche CC, Fuller DH, Montefiori DC, Stamatatos L, Sather DN, Haigwood NL. Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens. J Immunol. 2016 Apr 1;196(7):3064–3078.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

April 1, 2016

Volume

196

Issue

7

Start / End Page

3064 / 3078

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccination
  • T-Lymphocyte Subsets
  • Neutralization Tests
  • Macaca mulatta
  • Lymphoid Tissue
  • Immunology
  • Immunoglobulin G
  • Immunization Schedule
  • Immunization