title: Correlation of Antibody Responses to a Peptide Antigen gp120-C5501-512/gp41732-744with HIV Disease Progression.
abstract: Antibodies to the carboxy-terminal constant (C5) region 5 of the HIV-1 envelope glycoprotein gp120 have previously been associated with slow disease progression. This is one of the regions on gp120 that interact with the transmembrane glycoprotein, gp41, anchoring it to the viral and infected cell membrane. This study analyzed humoral responses to a novel heterodimeric peptide construct comprising the C5501-512region and a compatible region on gp41732-744. Antibody levels to C5501-512/gp41732-744were associated with slow disease progression in a treatment naive historical longitudinal cohort from Norway (n = 32; p = .00001). Elevated anti-C5501-512/gp41732-744antibody levels correlated with moderate viral load (VL) (50-10,000 copies/ml) in a cohort, including natural viral suppressors (NVS) in the Unites States (n = 58; p = .002). Analysis of HIV-positive sera from treatment naive patients in Estonia (n = 300) showed an inverse correlation between anti-C5501-512/gp41732-744antibodies and VL when comparing VL 2,000-10,000 copies/ml with VL >10,000 (p = .050). Further mapping using peptide inhibition of antibody binding revealed that responses to the C5501-506subdomain correlated with preserved CD4 counts (n = 55; p = .0012) irrespective of VL in this cohort. The C5 region encompassing C5501-506shows sequence similarity to the shared epitope (SE) of certain HLA-DR associated with immune dysfunction. Partial antigenic cross-reactivity between SE and C5 is indicated by partial inhibition of NVS antibody binding using SE 15-mer peptide (median 65% inhibition), the C5501-5066-mer peptide (79% inhibition), and binding of rheumatoid arthritis patient sera to both SE and C5 peptide sequences. The potential influence of these observations on HIV-1 pathogenesis remains to be determined.
authors.affiliation: 1 Bionor Pharma AS , Oslo, Norway .
authors.forename: Birger
authors.initials: B
authors.lastname: Sørensen
authors.affiliation: 1 Bionor Pharma AS , Oslo, Norway .
authors.forename: Maja A
authors.initials: MA
authors.lastname: Sommerfelt
authors.affiliation: 1 Bionor Pharma AS , Oslo, Norway .
authors.forename: Grete
authors.initials: G
authors.lastname: Stjernholm
authors.affiliation: 2 St. George's, University of London , Institute of Infection and Immunity, London, United Kingdom .
authors.forename: Peter Lawrence
authors.initials: PL
authors.lastname: Smith
authors.affiliation: 1 Bionor Pharma AS , Oslo, Norway .
authors.forename: Mats
authors.initials: M
authors.lastname: Ökvist
authors.affiliation: 1 Bionor Pharma AS , Oslo, Norway .
authors.forename: Arnt-Ove
authors.initials: AO
authors.lastname: Hovden
authors.affiliation: 3 Department of Virology, The Norwegian Institute of Public Health , Oslo, Norway .
authors.forename: Gunnar
authors.initials: G
authors.lastname: Hoddevik
authors.affiliation: 4 Department of Medicine, Institute of Human Virology, University of Maryland School of Medicine , Baltimore, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Redfield
authors.affiliation: 5 State Reference Laboratory of HIV Diagnostics, West-Tallinn Central Hospital , Estonia .
authors.forename: Valentina
authors.initials: V
authors.lastname: Ustina
authors.affiliation: 6 Bionor Laboratories AS , Skien, Norway .
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Jelmert
authors.affiliation: 7 Celgene Corp./Celgene Global Health , Summit, New Jersey.
authors.forename: Jerome
authors.initials: J
authors.lastname: Zeldis
authors.affiliation: 2 St. George's, University of London , Institute of Infection and Immunity, London, United Kingdom .
authors.forename: Angus
authors.initials: A
authors.lastname: Dalgleish
mesh_terms: D000917:Antibody Formation; D015331:Cohort Studies; D018450:Disease Progression; D015483:HIV Antibodies / Q000097:blood*; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans
chemical_list: D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; C514793:gp120 protein, Human immunodeficiency virus 1; C514787:gp41 protein, Human immunodeficiency virus 1
keywords: HIV envelope glycoproteins; HIV pathogenesis; antibody; immune activation; immune response