Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection

Hraber, Petera; Seaman, Michael S.b; Bailer, Robert T.c; Mascola, John R.c; Montefiori, David C.d; Korber, Bette T.a

AIDS:
doi: 10.1097/QAD.0000000000000106
Basic Science
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Abstract

Objective: Studies of neutralizing antibodies in HIV-1 infected individuals provide insights into the quality of the response that should be possible to elicit with vaccines and ways to design effective immunogens. Some individuals make high titres of exceptional broadly reactive neutralizing antibodies that are of particular interest; however, more modest responses may be a reasonable goal for vaccines. We performed a large cross-sectional study to determine the spectrum of neutralization potency and breadth that is seen during chronic HIV-1 infection.

Design: Neutralization potency and breadth were assessed with genetically and geographically diverse panels of 205 chronic HIV-1 sera and 219 Env-pseudotyped viruses representing all major genetic subtypes of HIV-1.

Methods: Neutralization was measured by using Tat-regulated luciferase reporter gene expression in TZM-bl cells. Serum-neutralizing activity was compared with a diverse set of human mAbs that are widely considered to be broadly neutralizing.

Results: We observed a uniform continuum of responses, with most sera displaying some level of cross-neutralization, and approximately 50% of sera neutralizing more than 50% of viruses. Titres of neutralization (potency) were highly correlated with breadth. Many sera had breadth comparable to several of the less potent broadly neutralizing human mAbs.

Conclusion: These results help clarify the spectrum of serum-neutralizing activity induced by HIV-1 infection and that should be possible to elicit with vaccines. Importantly, most people appear capable of making low to moderate titres of broadly neutralizing antibodies. Additional studies of these relatively common responses might provide insights for practical and feasible vaccine designs.

Author Information

aTheoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico

bCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

cVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

dDepartment of Surgery, Duke University Medical Center, Durham, North Carolina, USA.

Correspondence to David C. Montefiori, Duke University Medical Center, Durham, NC 27710, USA. E-mail: monte@duke.edu

Received 25 July, 2013

Revised 7 October, 2013

Accepted 7 October, 2013

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© 2014 Lippincott Williams & Wilkins, Inc.