scholarly journals Development of a high-throughput bead based assay system to measure HIV-1 specific immune signatures in clinical samples

2017 ◽  
Author(s):  
Thomas Liechti ◽  
Claus Kadelka ◽  
Hanna Ebner ◽  
Nikolas Friedrich ◽  
Roger D. Kouyos ◽  
...  
Keyword(s):  
High Throughput ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Assay System ◽  
Clinical Samples ◽  
Correlates Of Protection ◽  
Technical Advances ◽  
Broadly Neutralizing Antibody ◽  
Binding Antibody ◽  
Hiv 1

AbstractThe monitoring and assessment of a broadly neutralizing antibody (bnAb) based HIV-1 vaccine require detailed measurements of HIV-1 binding antibody responses to support the detection of correlates of protection. Here we describe the development of a flexible, high-throughput microsphere based multiplex assay system that allows monitoring complex binding antibody signatures. Studying a panel of 13 HIV-1 antigens in a parallel assessment of different IgG subclasses (IgG1, IgG2 and IgG3) we demonstrate the potential of our strategy. The technical advances we describe include means to improve antigen reactivity using directed neutravidin-biotin immobilization of antigens and biotin saturation to reduce background. A particular emphasis of our study was to provide tools for the assessment of reproducibility and stability of the assay system and strategies to control for variations allowing the application in high-throughput assays, where reliability of single measurements needs to be guaranteed.

scholarly journals Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity

2018 ◽  
Vol 215 (6) ◽  
pp. 1589-1608 ◽  
Author(s):  
Claus Kadelka ◽  
Thomas Liechti ◽  
Hanna Ebner ◽  
Merle Schanz ◽  
Peter Rusert ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Igg Subclass ◽  
Dependent Manner ◽  
Immune Modulators ◽  
Broadly Neutralizing Antibody ◽  
Binding Antibody ◽  
Hiv 1 ◽  
Disease Parameters

Understanding pathways that promote HIV-1 broadly neutralizing antibody (bnAb) induction is crucial to advance bnAb-based vaccines. We recently demarcated host, viral, and disease parameters associated with bnAb development in a large HIV-1 cohort screen. By establishing comprehensive antibody signatures based on IgG1, IgG2, and IgG3 activity to 13 HIV-1 antigens in 4,281 individuals in the same cohort, we now show that the same four parameters that are significantly linked with neutralization breadth, namely viral load, infection length, viral diversity, and ethnicity, also strongly influence HIV-1–binding antibody responses. However, the effects proved selective, shaping binding antibody responses in an antigen and IgG subclass–dependent manner. IgG response landscapes in bnAb inducers indicated a differentially regulated, IgG1-driven HIV-1 antigen response, and IgG1 binding of the BG505 SOSIP trimer proved the best predictor of HIV-1 neutralization breadth in plasma. Our findings emphasize the need to unravel immune modulators that underlie the differentially regulated IgG response in bnAb inducers to guide vaccine development.

scholarly journals Immunogenicity, safety and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs

2020 ◽  
Author(s):  
Blasi Maria ◽  
Negri Donatella ◽  
Saunders O Kevin ◽  
Baker J Erich ◽  
Stadtler Hannah ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Lentiviral Vector ◽  
Rhesus Macaques ◽  
Infected Individual ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Safety And Efficacy ◽  
Broadly Neutralizing Antibody ◽  
Env Protein ◽  
Hiv 1

AbstractA preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study we report the immunogenicity, safety and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Env induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/- protein immunizations using the same sequential envelopes. Compared to monkeys immunized with vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six month after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Our results show that while IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms, the use of non-stabilized sequential envelope trimers did not induce broadly neutralizing antibody responses.

scholarly journals Lower Broadly Neutralizing Antibody Responses in Female Versus Male HIV-1 Infected Injecting Drug Users

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 384
Author(s):  
Zelda EULER ◽  
Tom L. VAN DEN KERKHOF ◽  
Roger D. KOUYOS ◽  
Damien C. TULLY ◽  
Todd M. ALLEN ◽  
...  
Keyword(s):  
Drug Users ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Injecting Drug Users ◽  
Antibody Responses ◽  
Multiple Factors ◽  
Efficacy Trials ◽  
Female Idus ◽  
Broadly Neutralizing Antibody ◽  
Hiv 1

Understanding the factors involved in the development of broadly neutralizing antibody (bNAb) responses in natural infection can guide vaccine design aimed at eliciting protective bNAb responses. Most of the studies to identify and study the development of bNAb responses have been performed in individuals who had become infected via homo- or heterosexual HIV-1 transmission; however, the prevalence and characteristics of bNAb responses in injecting drug users (IDUs) have been underrepresented. We retrospectively studied the prevalence of bNAb responses in HIV-1 infected individuals in the Amsterdam Cohort, including 50 male and 35 female participants who reported injecting drug use as the only risk factor. Our study revealed a significantly lower prevalence of bNAb responses in females compared to males. Gender, transmission route and CD4+ count at set point, but not viral load, were independently associated with the development of bNAb responses in IDUs. To further explore the influences of gender in the setting of IDU, we also looked into the Swiss 4.5k Screen. There we observed lower bNAb responses in female IDUs as well. These results reveal that the emergence of bNAbs may be dependent on multiple factors, including gender. Therefore, the effect of gender on the development of bNAb responses is a factor that should be taken into account when designing vaccine efficacy trials.

scholarly journals Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors

PLoS ONE ◽  
2018 ◽  
Vol 13 (3) ◽  
pp. e0193773 ◽  
Author(s):  
Nuria González ◽  
Krisha McKee ◽  
Rebecca M. Lynch ◽  
Ivelin S. Georgiev ◽  
Laura Jimenez ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibody ◽  
Hiv 1

scholarly journals Tracing HIV-1 strains that imprint broadly neutralizing antibody responses

Nature ◽  
2018 ◽  
Vol 561 (7723) ◽  
pp. 406-410 ◽  
Author(s):  
Roger D. Kouyos ◽  
◽  
Peter Rusert ◽  
Claus Kadelka ◽  
Michael Huber ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibody ◽  
Hiv 1

scholarly journals Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection

AIDS ◽  
2014 ◽  
Vol 28 (2) ◽  
pp. 163-169 ◽  
Author(s):  
Peter Hraber ◽  
Michael S. Seaman ◽  
Robert T. Bailer ◽  
John R. Mascola ◽  
David C. Montefiori ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibody ◽  
Hiv 1

scholarly journals Coadministration of CH31 Broadly Neutralizing Antibody Does Not Affect Development of Vaccine-Induced Anti-HIV-1 Envelope Antibody Responses in Infant Rhesus Macaques

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Maria Dennis ◽  
Joshua Eudailey ◽  
Justin Pollara ◽  
Arthur S. McMillan ◽  
Kenneth D. Cronin ◽  
...  
Keyword(s):  
De Novo ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Mother To Child Transmission ◽  
Child Transmission ◽  
Broadly Neutralizing Antibody ◽  
Env Protein ◽  
The Impact ◽  
Mother To Child ◽  
Hiv 1

ABSTRACT Prevention of mother-to-child transmission (MTCT) is an indispensable component in combatting the global AIDS epidemic. A combination of passive broadly neutralizing antibody (bnAb) infusion and active vaccination promises to provide protection of infants against MTCT from birth through the breastfeeding period and could prime the immune system for lifelong immunity. In this study, we investigate the impact of a single infusion of CD4 binding site (CD4bs) bnAb administered at birth on de novo antibody responses elicited by concurrent active HIV envelope vaccination. Four groups of infant macaques received active immunizations with subunit Env protein or modified vaccinia Ankara (MVA)-vectored Env and subunit Env protein, with or without a single intravenous coadministration of CH31 bnAb at birth. Vaccinated animals were monitored to evaluate binding and functional antibody responses elicited by the active vaccinations. Despite achieving plasma concentrations that were able to neutralize tier 2 viruses, coadministration of CH31 did not have a large impact on the kinetics, magnitude, specificity, or avidity of vaccine-elicited binding or functional antibody responses, including epitope specificity, the development of CD4bs antibodies, neutralization, binding to infected cells, or antibody-dependent cell-mediated cytotoxicity (ADCC). We conclude that infusion of CD4bs bnAb CH31 at birth does not interfere with de novo antibody responses to active vaccination and that a combination of passive bnAb infusion and active HIV-1 Env vaccination is a viable strategy for immediate and prolonged protection against MTCT. IMPORTANCE Our study is the first to evaluate the impact of passive infusion of a broadly neutralizing antibody in newborns on the de novo development of antibody responses following active vaccinations in infancy. We demonstrated the safety and the feasibility of bnAb administration to achieve biologically relevant levels of the antibody and showed that the passive infusion did not impair the de novo antibody production following HIV-1 Env vaccination. Our study paves the way for further investigations of the combination strategy using passive plus active immunization to provide protection of infants born to HIV-1-positive mothers over the entire period of risk for mother-to-child transmission.

The Impact of Antiretroviral Treatment on HIV-1-Specific Broadly Neutralizing Antibody Responses

2014 ◽  
Vol 30 (S1) ◽  
pp. A77-A77
Author(s):  
Nonhlanhla N. Mkhize ◽  
Maphuti Madiga ◽  
Raveshni Durgiah ◽  
Elin S. Gray ◽  
Penny L. Moore ◽  
...  
Keyword(s):  
Antiretroviral Treatment ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibody ◽  
The Impact ◽  
Hiv 1
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