immune response; neutralization; HIV; vaccine; large nested project (SHCS)
Liechti Thomas, Kadelka Claus, Braun Dominique L., Kuster Herbert, Böni Jürg, Robbiani Melissa, Günthard Huldrych F., Trkola Alexandra (2019), Widespread B cell perturbations in HIV-1 infection afflict naive and marginal zone B cells, in The Journal of Experimental Medicine
, 216(9), 2071-2090.
EULER Zelda, VAN DEN KERKHOF Tom L., KOUYOS Roger D., TULLY Damien C., ALLEN Todd M., TRKOLA Alexandra, SANDERS Rogier W., SCHUITEMAKER Hanneke, VAN GILS Marit J. (2019), Lower Broadly Neutralizing Antibody Responses in Female Versus Male HIV-1 Infected Injecting Drug Users, in Viruses
, 11(4), 384-384.
Ivan Branislav, Sun Zhaozhi, Subbaraman Harini, Friedrich Nikolas, Trkola Alexandra (2019), CD4 occupancy triggers sequential pre-fusion conformational states of the HIV-1 envelope trimer with relevance for broadly neutralizing antibody activity, in PLOS Biology
, 17(1), e3000114-e3000114.
Kouyos Roger D., Rusert Peter, Kadelka Claus, Huber Michael, Marzel Alex, Ebner Hanna, Schanz Merle, Liechti Thomas, Friedrich Nikolas, Braun Dominique L., Scherrer Alexandra U., Weber Jacqueline, Uhr Therese, Baumann Nicolas S., Leemann Christine, Kuster Herbert, Chave Jean-Philippe, Cavassini Matthias, Bernasconi Enos, Hoffmann Matthias, Calmy Alexandra, Battegay Manuel, Rauch Andri, Yerly Sabine, Aubert Vincent, KlimkaitThomas, BöniJürg, MetznerKarin, GünthardHuldrych, TrkolaAlexandra, the Swiss HIV Cohort (2018), Tracing HIV-1 strains that imprint broadly neutralizing antibody responses, in Nature
, 561(7723), 406-410.
Liechti Thomas, Günthard Huldrych F., Trkola Alexandra (2018), OMIP-047: High-Dimensional phenotypic characterization of B cellsOMIP-047, in Cytometry Part A
, 93(6), 592-596.
Beauparlant David, Rusert Peter, Magnus Carsten, Kadelka Claus, Weber Jacqueline, Uhr Therese, Zagordi Osvaldo, Oberle Corinna, Duenas-Decamp Maria J, Clapham Paul R, Metzner Karin J, Günthard Huldrych F, Trkola Alexandra (2017), Delineating CD4 dependency of HIV-1: Adaptation to infect low level CD4 expressing target cells widens cellular tropism but severely impacts on envelope functionality., in PLoS pathogens
, 13(3), 1006255-1006255.
Rusert Peter, Kouyos Roger D, Kadelka Claus, Ebner Hanna, Schanz Merle, Huber Michael, Braun Dominique L, Hozé Nathanael, Scherrer Alexandra, Magnus Carsten, Weber Jacqueline, Uhr Therese, Cippa Valentina, Thorball Christian W, Kuster Herbert, Cavassini Matthias, Bernasconi Enos, Hoffmann Matthias, Calmy Alexandra, Battegay Manuel, Rauch Andri, Yerly Sabine, Aubert Vincent, Klimkait Thomas, Böni Jürg (2016), Determinants of HIV-1 broadly neutralizing antibody induction., in Nature medicine
, 22(11), 1260-1267.
Magnus Carsten, Reh Lucia, Trkola Alexandra (2016), HIV-1 resistance to neutralizing antibodies: Determination of antibody concentrations leading to escape mutant evolution., in Virus Research
, 218, 57-70.
Oberle Corinna S, Joos Beda, Rusert Peter, Campbell Nottania K, Beauparlant David, Kuster Herbert, Weber Jacqueline, Schenkel Corinne D, Scherrer Alexandra U, Magnus Carsten, Kouyos Roger, Rieder Philip, Niederöst Barbara, Braun Dominique L, Pavlovic Jovan, Böni Jürg, Yerly Sabine, Klimkait Thomas, Aubert Vincent, Trkola Alexandra, Metzner Karin J, Günthard Huldrych F, Günthard Huldrych F (2016), Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs., in Retrovirology
, 13(1), 62-62.
Brandenberg Oliver F., Magnus Carsten, Regoes Roland R., Trkola Alexandra (2015), The HIV-1 Entry Process: A Stoichiometric View, in Trends in Microbiology
, 23(12), 763-774.
Reh Lucia, Magnus Carsten, Schanz Merle, Weber Jacqueline, Uhr Therese, Rusert Peter, Trkola Alexandra (2015), Capacity of Broadly Neutralizing Antibodies to Inhibit HIV-1 Cell-Cell Transmission Is Strain- and Epitope-Dependent., in PLoS pathogens
, 11(7), 1004966-1004966.
Brandenberg Oliver F, Magnus Carsten, Rusert Peter, Regoes Roland R, Trkola Alexandra (2015), Different infectivity of HIV-1 strains is linked to number of envelope trimers required for entry., in PLoS pathogens
, 11(1), 1004595-1004595.
Schanz Merle, Liechti Thomas, Zagordi Osvaldo, Miho Enkelejda, Reddy Sai T., Günthard Huldrych F., Trkola Alexandra, Huber Michael (2014), High-Throughput Sequencing of Human Immunoglobulin Variable Regions with Subtype Identification, in PLoS ONE
, 9(11), e111726-e111726.
Building on recent discoveries in the HIV antibody field, we propose here to conduct a systematic screen for broadly neutralizing antibody (bNAb) activity elicited during HIV infection using the extensive sample and data collection of the Swiss HIV Cohort Study. By assessing the neutralization breadth in approx. 3800 closely monitored individuals at different disease stages spanning the HIV infection of the past 25 years, we will have a unique possibility to address many aspects of neutralizing antibody evolution in HIV infection that urgently await clarification. In order to learn why bNAbs are so rarely induced in natural infection and to unravel how to induce them by vaccination, we need to identify and characterize more bNAbs, define their ontogeny, study their evolution over time and ideally, derive alongside information on the co-evolving viral envelope gene. A main goal of our study is to obtain insights why bNAb induction is generally rare in HIV infection. The comprehensive patient data and specimen that are available within the investigated patient cohorts will empower our study to perform extended systematic and longitudinal analyses that go beyond a mere frequency analysis of antibody responses and have the possibility to confirm and to rule out potential viral, host and disease linked co-factors of bNAb induction.Aim A focusses on the screening of the cohort for patients with broadly neutralizing plasma activity, determination of their binding antibody profiles and prediction of the recognized neutralization epitopes. This large screen is possible due to recent technical advances in the antibody discovery field that we will employ here, in particular a combination of high-throughput neutralization and binding antibody assays and computational prediction algorithms which allows to retrieve neutralizing antibody epitope information directly from plasma analysis. Finally, and most importantly, these data will be utilized to probe association of bNAb induction with viral, host and disease parameters. Within Aim B we propose to clone bNAbs from patients with top neutralizing activity in plasma and to study the ontogeny of these antibodies longitudinally alongside the autologous virus strain. Aim C focusses specifically on MPER specific antibodies. Here we seek to explore the factors that are associated with induction of this type of antibodies and to study their potential association with viral, host and disease factors. A particular emphasis will be on investigating the frequencies and phenotype of IgG1 and IGG3 MPER responses, as the MPER specific bNAbs are all of the otherwise amongst HIV envelope antibody uncommon IgG3 subclass. Secondly, we will investigate a potential association with autoreactive antibodies induced during HIV infection as several MPER antibodies are described to be strongly autoreactive. An in depth analysis of which viral, host and disease factors allow the emergence of bNAbs as we propose to conduct here is critical to harness these types for antibodies for vaccines.