HIV-1 subtype C superinfected individuals mount low autologous neutralizing antibody responses prior to intrasubtype superinfection

• Published in: Retrovirology Vol. 9; no. 1; p. 76
• Main Authors: Basu, Debby, Kraft, Colleen S, Murphy, Megan K, Campbell, Patricia J, Yu, Tianwei, Hraber, Peter T, Irene, Carmela, Pinter, Abraham, Chomba, Elwyn, Mulenga, Joseph, Kilembe, William, Allen, Susan A, Derdeyn, Cynthia A, Hunter, Eric
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.09.2012; BioMed Central; BMC
• Subjects: Acquired immune deficiency syndrome; AIDS; Antibodies; Antibodies, Neutralizing - blood; BASIC BIOLOGICAL SCIENCES; Case-Control Studies; Cell Line; Comparative analysis; Development and progression; Disease transmission; Genetic aspects; Genomes; Genomics; Health aspects; HIV; HIV (Viruses); HIV Antibodies - blood; HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp120 - immunology; HIV infection; HIV Infections - blood; HIV Infections - immunology; HIV Infections - virology; HIV-1 - genetics; HIV-1 - immunology; HIV-1 dual infection; HIV-1 superinfection; HIV-1 transmission; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immune response; Immunity, Humoral; Immunoglobulin A; Immunoglobulin A - blood; Immunoglobulin G; Immunoglobulin G - blood; Infection; Infections; Medical research; Molecular Sequence Data; Neutralizing antibodies; Peptide Fragments - immunology; Phylogeography; Physiological aspects; Plasma; Risk factors; Sequence Analysis, DNA; Studies; Subtype C; Superinfection - virology; Vaccines; Viral antibodies; Virology; United States; Atlanta Georgia; Georgia
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/1742-4690-9-76

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. 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. 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.