title: Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection.
abstract: A fraction of HIV-1 patients are able to generate broadly neutralizing antibodies (bNAbs) after 2 to 4 years of infection. In rare occasions such antibodies are observed close to the first year of HIV-1 infection but never within the first 6 months. In this study, we analyzed the neutralization breadth of sera from 157 antiretroviral-naive individuals who were infected for less than 1 year. A range of neutralizing activities was observed with a previously described panel of six recombinant viruses from five different subtypes (M. Medina-Ramirez et al., J Virol 85:5804-5813, 2011, http://dx.doi.org/10.1128/JVI.02482-10). Some sera were broadly reactive, predominantly targeting envelope epitopes within the V2 glycan-dependent region. The neutralization breadth was positively associated with time postinfection (P = 0.0001), but contrary to what has been reported for chronic infections, no association with the viral load was observed. Notably, five individuals within the first 6 months of infection (two as early as 77 and 96 days postinfection) showed substantial cross-neutralization. This was confirmed with an extended panel of 20 Env pseudoviruses from four different subtypes (two in tier 3, 14 in tier 2, and four in tier 1). Sera from these individuals were capable of neutralizing viruses from four different subtypes with a geometric mean 50% infective dose (ID50) between 100 and 800. These results indicate that induction of cross-neutralizing responses, albeit rare, is achievable even within 6 months of HIV-1 infection. These observations encourage the search for immunogens able to elicit this kind of response in preventive HIV-1 vaccine approaches.
  
  
  
  There are very few individuals able to mount broadly neutralizing activity (bNA) close to the first year postinfection. It is not known how early in the infection cross-neutralizing responses can be induced. In the present study, we show that bNAbs, despite being rare, can be induced much earlier than previously thought. The identification of HIV-1-infected patients with these activities within the first months of infection and characterization of these responses will help in defining new immunogen designs and neutralization targets for vaccine-mediated induction of bNAbs.
authors.affiliation: AIDS Research Unit, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain vmsanchez@clinic.ub.es.|HIVACAT, Barcelona, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Sanchez-Merino
authors.affiliation: AIDS Research Unit, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|HIVACAT, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fabra-Garcia
authors.affiliation: AIDS Immunopathogenesis Unit, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Gonzalez
authors.affiliation: Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Nicolas
authors.affiliation: AIDS Research Unit, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|HIVACAT, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Merino-Mansilla
authors.affiliation: Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Manzardo
authors.affiliation: Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Ambrosioni
authors.affiliation: Fraunhofer Institute for Biomedical Engineering, Sulzbach, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schultz
authors.affiliation: Infection Biology Laboratory, Universitat Pompeu Fabra, and Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Meyerhans
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: AIDS Immunopathogenesis Unit, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Alcami
authors.affiliation: Infectious Diseases Service, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Miro
authors.affiliation: AIDS Research Unit, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|HIVACAT, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Yuste
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology*; D003430:Cross-Sectional Studies; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008297:Male; D009500:Neutralization Tests; D011134:Polysaccharides / Q000276:immunology; D013997:Time Factors; D019562:Viral Load
chemical_list: D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D011134:Polysaccharides