Browsing by Subject "Antigen-Antibody Reactions"

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    Computational analysis of antibody dynamics identifies recent HIV-1 infection.
    (JCI insight, 2017-12-21) Seaton, Kelly E; Vandergrift, Nathan A; Deal, Aaron W; Rountree, Wes; Bainbridge, John; Grebe, Eduard; Anderson, David A; Sawant, Sheetal; Shen, Xiaoying; Yates, Nicole L; Denny, Thomas N; Liao, Hua-Xin; Haynes, Barton F; Robb, Merlin L; Parkin, Neil; Santos, Breno R; Garrett, Nigel; Price, Matthew A; Naniche, Denise; Duerr, Ann C; CEPHIA group; Keating, Sheila; Hampton, Dylan; Facente, Shelley; Marson, Kara; Welte, Alex; Pilcher, Christopher D; Cohen, Myron S; Tomaras, Georgia D
    Accurate HIV-1 incidence estimation is critical to the success of HIV-1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI). Dynamic early HIV-1 antibody response kinetics were harnessed to identify biomarkers for improved incidence assays. We conducted retrospective analyses on circulating antibodies from known recent and longstanding infections and evaluated binding and avidity measurements of Env and non-Env antigens and multiple antibody forms (i.e., IgG, IgA, IgG3, IgG4, dIgA, and IgM) in a diverse panel of 164 HIV-1-infected participants (clades A, B, C). Discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. Thus, computational analysis of dynamic HIV-1 antibody isotype and antigen interactions during infection enabled design of a promising HIV-1 recency assay for improved cross-sectional incidence estimation.
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    Multiple HIV-1-specific IgG3 responses decline during acute HIV-1: implications for detection of incident HIV infection.
    (AIDS, 2011-11-13) Yates, Nicole L; Lucas, Judith T; Nolen, Tracy L; Vandergrift, Nathan A; Soderberg, Kelly A; Seaton, Kelly E; Denny, Thomas N; Haynes, Barton F; Cohen, Myron S; Tomaras, Georgia D
    OBJECTIVE: Different HIV-1 antigen specificities appear in sequence after HIV-1 transmission and the immunoglobulin G (IgG) subclass responses to HIV antigens are distinct from each other. The initial predominant IgG subclass response to HIV-1 infection consists of IgG1 and IgG3 antibodies with a noted decline in some IgG3 antibodies during acute HIV-1 infection. Thus, we postulate that multiple antigen-specific IgG3 responses may serve as surrogates for the relative time since HIV-1 acquisition. DESIGN: We determined the magnitude, peak, and half-life of HIV-1 antigen-specific IgG1 and IgG3 antibodies in 41 HIV-1-infected individuals followed longitudinally from acute infection during the first appearance of HIV-1-specific antibodies through approximately 6 months after infection. METHODS: We used quantitative HIV-1-binding antibody multiplex assays and exponential decay models to estimate concentrations of IgG1 and IgG3 antibodies to eight different HIV-1 proteins including gp140 Env, gp120 Env, gp41 Env, p66 reverse transcriptase, p31 Integrase, Tat, Nef, and p55 Gag proteins during acute/recent HIV-1 infection. RESULTS: Among HIV-1-specific IgG3 responses, anti-gp41 IgG3 antibodies were the first to appear. We found that anti-gp41 Env IgG3 and anti-p66 reverse transcriptase IgG3 antibodies, in addition to anti-Gag IgG3 antibodies, each consistently and measurably declined after acute infection, in contrast to the persistent antigen-specific IgG1 responses. CONCLUSION: The detailed measurements of the decline in multiple HIV-specific IgG3 responses simultaneous with persistent IgG1 responses during acute and recent HIV-1 infection could serve as markers for detection of incident HIV infection.
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    Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.
    (PLoS One, 2015) Joachim, Agricola; Nilsson, Charlotta; Aboud, Said; Bakari, Muhammad; Lyamuya, Eligius F; Robb, Merlin L; Marovich, Mary A; Earl, Patricia; Moss, Bernard; Ochsenbauer, Christina; Wahren, Britta; Mhalu, Fred; Sandström, Eric; Biberfeld, Gunnel; Ferrari, Guido; Polonis, Victoria R
    UNLABELLED: Vaccine-induced HIV antibodies were evaluated in serum samples collected from healthy Tanzanian volunteers participating in a phase I/II placebo-controlled double blind trial using multi-clade, multigene HIV-DNA priming and recombinant modified vaccinia Ankara (HIV-MVA) virus boosting (HIVIS03). The HIV-DNA vaccine contained plasmids expressing HIV-1 gp160 subtypes A, B, C, Rev B, Gag A, B and RTmut B, and the recombinant HIV-MVA boost expressed CRF01_AE HIV-1 Env subtype E and Gag-Pol subtype A. While no neutralizing antibodies were detected using pseudoviruses in the TZM-bl cell assay, this prime-boost vaccination induced neutralizing antibodies in 83% of HIVIS03 vaccinees when a peripheral blood mononuclear cell (PBMC) assay using luciferase reporter-infectious molecular clones (LucR-IMC) was employed. The serum neutralizing activity was significantly (but not completely) reduced upon depletion of natural killer (NK) cells from PBMC (p=0.006), indicating a role for antibody-mediated Fcγ-receptor function. High levels of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies against CRF01_AE and/or subtype B were subsequently demonstrated in 97% of the sera of vaccinees. The magnitude of ADCC-mediating antibodies against CM235 CRF01_AE IMC-infected cells correlated with neutralizing antibodies against CM235 in the IMC/PBMC assay. In conclusion, HIV-DNA priming, followed by two HIV-MVA boosts elicited potent ADCC responses in a high proportion of Tanzanian vaccinees. Our findings highlight the potential of HIV-DNA prime HIV-MVA boost vaccines for induction of functional antibody responses and suggest this vaccine regimen and ADCC studies as potentially important new avenues in HIV vaccine development. TRIAL REGISTRATION: Controlled-Trials ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080 (currently PACTR2009040001075080).