title: The Neutralizing Antibody Response in an Individual with Triple HIV-1 Infection Remains Directed at the First Infecting Subtype.
abstract: The effect of serial HIV-1 infection on the development of the broadly neutralizing antibody (bNAb) response was studied in an individual, H01-10366, with a serial HIV-1 superinfection (SI), hence triple infection, and compared with the bNAb response in three superinfected as well as 11 monoinfected men who have had sex with men (MSM) from Amsterdam, the Netherlands. Neutralization assays measuring heterologous neutralizing antibody (NAb) titers on a panel of six representative viruses from different HIV-1 subtypes were performed on blood serum samples obtained ∼3 years after primary HIV infection (PHI) and longitudinally for H01-10366. A bNAb response was defined as having a geometric mean neutralization titer (the reciprocal serum dilution giving 50% inhibition of virus infection, inhibitory dilution (ID50)) ≥100 and neutralizing >50% of viruses in the panel with an ID50titer ≥100. H01-10366 quickly developed a potent NAb response against subtype B viruses before subtype B SI, but no broadening of the response occurred after the second subtype B infection or the third infection with CRF01_AE. When comparing H01-10366 with matched monoinfected (N = 11) and superinfected (N = 3) individuals analyzed 3 years after PHI, we found that 5 of the 15 individuals (4/11 monoinfected, 1/4 SI) developed a bNAb response. However, there was no statistically discernible difference between the bNAb response and HIV-1 SI. Thus, HIV-1 SI was not associated with the breadth and potency of the bNAb response in this small group of Dutch MSM with SI that included a triple HIV-1-infected individual.
authors.affiliation: 1 Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Marion
authors.initials: M
authors.lastname: Cornelissen
authors.affiliation: 2 Department of Experimental Immunology, Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Zelda
authors.initials: Z
authors.lastname: Euler
authors.affiliation: 1 Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .|2 Department of Experimental Immunology, Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Tom L G M
authors.initials: TL
authors.lastname: van den Kerkhof
authors.affiliation: 1 Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Marit J
authors.initials: MJ
authors.lastname: van Gils
authors.affiliation: 2 Department of Experimental Immunology, Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Brigitte D M
authors.initials: BD
authors.lastname: Boeser-Nunnink
authors.affiliation: 2 Department of Experimental Immunology, Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
authors.affiliation: 1 Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Fokla
authors.initials: F
authors.lastname: Zorgdrager
authors.affiliation: 2 Department of Experimental Immunology, Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: 3 Division of Infectious Diseases, Department of Internal Medicine, Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
authors.affiliation: 1 Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .|4 Department of Microbiology and Immunology, Weill Medical College, Cornell University , New York, New York.
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
authors.affiliation: 1 Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam , Amsterdam, the Netherlands .
authors.forename: Antoinette C
authors.initials: AC
authors.lastname: van der Kuyl
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology*; D000917:Antibody Formation; D060085:Coinfection / Q000276:immunology* / Q000821:virology; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009426:Netherlands; D009500:Neutralization Tests; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies
keywords: HIV-1; heterologous; men who have sex with men; neutralizing antibody; superinfection; triple infection