Achieving potent autologous neutralizing antibody responses against tier 2 HIV-1 viruses by strategic selection of envelope immunogens

Ann Hessell, Delphine Malherbe, Franco Pissani, Sean McBurney, Shelly J. Krebs, Michelle Gomes, Shilpi Pandey, William F. Sutton, Benjamin Burwitz, Matthew Gray, Harlan Robins, Byung Park, Jonah Sacha, Celia C. La Branche, Deborah H. Fuller, David C. Montefiori, Leonidas Stamatatos, D. Noah Sather, Nancy Haigwood

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3064-3078
Number of pages15
JournalJournal of Immunology
Volume196
Issue number7
DOIs
StatePublished - Apr 1 2016

Fingerprint

Macaca
Neutralizing Antibodies
Antibody Formation
HIV-1
AIDS Vaccines
Vaccines
Viruses
Immunoglobulin G
env Genes
Groin
Virus Diseases
Helper-Inducer T-Lymphocytes
Infection
Macaca mulatta
Immunization
Lymph Nodes
Lymphocytes
Phenotype
DNA
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Achieving potent autologous neutralizing antibody responses against tier 2 HIV-1 viruses by strategic selection of envelope immunogens. / Hessell, Ann; Malherbe, Delphine; Pissani, Franco; McBurney, Sean; Krebs, Shelly J.; Gomes, Michelle; Pandey, Shilpi; Sutton, William F.; Burwitz, Benjamin; Gray, Matthew; Robins, Harlan; Park, Byung; Sacha, Jonah; La Branche, Celia C.; Fuller, Deborah H.; Montefiori, David C.; Stamatatos, Leonidas; Sather, D. Noah; Haigwood, Nancy.

In: Journal of Immunology, Vol. 196, No. 7, 01.04.2016, p. 3064-3078.

Research output: Contribution to journalArticle

Hessell, A, Malherbe, D, Pissani, F, McBurney, S, Krebs, SJ, Gomes, M, Pandey, S, Sutton, WF, Burwitz, B, Gray, M, Robins, H, Park, B, Sacha, J, La Branche, CC, Fuller, DH, Montefiori, DC, Stamatatos, L, Sather, DN & Haigwood, N 2016, 'Achieving potent autologous neutralizing antibody responses against tier 2 HIV-1 viruses by strategic selection of envelope immunogens', Journal of Immunology, vol. 196, no. 7, pp. 3064-3078. https://doi.org/10.4049/jimmunol.1500527
Hessell, Ann ; Malherbe, Delphine ; Pissani, Franco ; McBurney, Sean ; Krebs, Shelly J. ; Gomes, Michelle ; Pandey, Shilpi ; Sutton, William F. ; Burwitz, Benjamin ; Gray, Matthew ; Robins, Harlan ; Park, Byung ; Sacha, Jonah ; La Branche, Celia C. ; Fuller, Deborah H. ; Montefiori, David C. ; Stamatatos, Leonidas ; Sather, D. Noah ; Haigwood, Nancy. / Achieving potent autologous neutralizing antibody responses against tier 2 HIV-1 viruses by strategic selection of envelope immunogens. In: Journal of Immunology. 2016 ; Vol. 196, No. 7. pp. 3064-3078.
@article{45328b2b9ba741539e4a38bbd2a13f8b,
title = "Achieving potent autologous neutralizing antibody responses against tier 2 HIV-1 viruses by strategic selection of envelope immunogens",
abstract = "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.",
author = "Ann Hessell and Delphine Malherbe and Franco Pissani and Sean McBurney and Krebs, {Shelly J.} and Michelle Gomes and Shilpi Pandey and Sutton, {William F.} and Benjamin Burwitz and Matthew Gray and Harlan Robins and Byung Park and Jonah Sacha and {La Branche}, {Celia C.} and Fuller, {Deborah H.} and Montefiori, {David C.} and Leonidas Stamatatos and Sather, {D. Noah} and Nancy Haigwood",
year = "2016",
month = "4",
day = "1",
doi = "10.4049/jimmunol.1500527",
language = "English (US)",
volume = "196",
pages = "3064--3078",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Achieving potent autologous neutralizing antibody responses against tier 2 HIV-1 viruses by strategic selection of envelope immunogens

AU - Hessell, Ann

AU - Malherbe, Delphine

AU - Pissani, Franco

AU - McBurney, Sean

AU - Krebs, Shelly J.

AU - Gomes, Michelle

AU - Pandey, Shilpi

AU - Sutton, William F.

AU - Burwitz, Benjamin

AU - Gray, Matthew

AU - Robins, Harlan

AU - Park, Byung

AU - Sacha, Jonah

AU - La Branche, Celia C.

AU - Fuller, Deborah H.

AU - Montefiori, David C.

AU - Stamatatos, Leonidas

AU - Sather, D. Noah

AU - Haigwood, Nancy

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84962605521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962605521&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1500527

DO - 10.4049/jimmunol.1500527

M3 - Article

C2 - 26944928

AN - SCOPUS:84962605521

VL - 196

SP - 3064

EP - 3078

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -