title: HIV-1 subtype C superinfected individuals mount low autologous neutralizing antibody responses prior to intrasubtype superinfection.
abstract: BACKGROUND
  The potential role of antibodies in protection against intra-subtype HIV-1 superinfection remains to be understood. We compared the early neutralizing antibody (NAb) responses in three individuals, who were superinfected within one year of primary infection, to ten matched non-superinfected controls from a Zambian cohort of subtype C transmission cases. Sequence analysis of single genome amplified full-length envs from a previous study showed limited diversification in the individuals who became superinfected with the same HIV-1 subtype within year one post-seroconversion. We hypothesized that this reflected a blunted NAb response, which may have made these individuals more susceptible to superinfection.
  
  
  RESULTS
  Neutralization assays showed that autologous plasma NAb responses to the earliest, and in some cases transmitted/founder, virus were delayed and had low to undetectable titers in all three superinfected individuals prior to superinfection. In contrast, NAbs with a median IC50 titer of 1896 were detected as early as three months post-seroconversion in non-superinfected controls. Early plasma NAbs in all subjects showed limited but variable levels of heterologous neutralization breadth. Superinfected individuals also exhibited a trend toward lower levels of gp120- and V1V2-specific IgG binding antibodies but higher gp120-specific plasma IgA binding antibodies.
  
  
  CONCLUSIONS
  These data suggest that the lack of development of IgG antibodies, as reflected in autologous NAbs as well as gp120 and V1V2 binding antibodies to the primary infection virus, combined with potentially competing, non-protective IgA antibodies, may increase susceptibility to superinfection in the context of settings where a single HIV-1 subtype predominates.
authors.affiliation: Immunology and Molecular Pathogenesis Graduate Program, Emory University, Atlanta, GA, USA.
authors.forename: Debby
authors.initials: D
authors.lastname: Basu
authors.forename: Colleen S
authors.initials: CS
authors.lastname: Kraft
authors.forename: Megan K
authors.initials: MK
authors.lastname: Murphy
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Campbell
authors.forename: Tianwei
authors.initials: T
authors.lastname: Yu
authors.forename: Peter T
authors.initials: PT
authors.lastname: Hraber
authors.forename: Carmela
authors.initials: C
authors.lastname: Irene
authors.forename: Abraham
authors.initials: A
authors.lastname: Pinter
authors.forename: Elwyn
authors.initials: E
authors.lastname: Chomba
authors.forename: Joseph
authors.initials: J
authors.lastname: Mulenga
authors.forename: William
authors.initials: W
authors.lastname: Kilembe
authors.forename: Susan A
authors.initials: SA
authors.lastname: Allen
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Derdeyn
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood*; D016022:Case-Control Studies; D002460:Cell Line; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D056724:Immunity, Humoral; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D058974:Phylogeography; D017422:Sequence Analysis, DNA; D015163:Superinfection / Q000821:virology*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010446:Peptide Fragments; C514793:gp120 protein, Human immunodeficiency virus 1