large nested project SHCS; HIV; immune response; large nested project SHCS; vaccine; neutralization
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.
Abela Irene A., Kadelka Claus, Trkola Alexandra (2019), Correlates of broadly neutralizing antibody development, in Current Opinion in HIV and AIDS
, 14(4), 279-285.
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.
Subbaraman Harini, Schanz Merle, Trkola Alexandra (2018), Broadly neutralizing antibodies: What is needed to move from a rare event in HIV-1 infection to vaccine efficacy?, in Retrovirology
, 15(1), 52-52.
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.
Kadelka Claus, Liechti Thomas, Ebner Hanna, Schanz Merle, Rusert Peter, Friedrich Nikolas, Stiegeler Emanuel, Braun Dominique L., Huber Michael, Scherrer Alexandra U., Weber Jacqueline, Uhr Therese, Kuster Herbert, Misselwitz Benjamin, Cavassini Matthias, Bernasconi Enos, Hoffmann Matthias, Calmy Alexandra, Battegay Manuel, Rauch Andri, Yerly Sabine, Aubert Vincent, Klimkait Thomas, Böni Jürg, Kouyos Roger, GünthardHuldrych, TrkolaAlexandra, the Swiss HIV Cohort (2018), Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity, in The Journal of Experimental Medicine
, 215(6), 1589-1608.
Liechti Thomas, Kadelka Claus, Ebner Hanna, Friedrich Nikolas, Kouyos Roger D., Günthard Huldrych F., Trkola Alexandra (2018), Development of a high-throughput bead based assay system to measure HIV-1 specific immune signatures in clinical samples, in Journal of Immunological Methods
, 454, 48-58.
Reh Lucia, Magnus Carsten, Kadelka Claus, Kühnert Denise, Uhr Therese, Weber Jacqueline, Morris Lynn, Moore Penny L., Trkola Alexandra (2018), Phenotypic deficits in the HIV-1 envelope are associated with the maturation of a V2-directed broadly neutralizing antibody lineage, in PLOS Pathogens
, 14(1), e1006825-e1006825.
Over the previous grant period we conducted a systematic survey of broadly neutralizing antibody (bnAb) activity in 4,484 HIV-1 infected individuals enrolled in two Swiss HIV cohorts, the Swiss HIV Cohort Study (SHCS) and the Zurich Primary HIV Infection Study (ZPHI). This largest HIV bnAb survey to date, now termed the Swiss 4.5K Screen, made several important and thought-provoking observations (see Rusert, Kouyos et al Nat Med 2016). In the current grant application we will continue the analysis of the Swiss 4.5K Screen, exploring additional parameters and concepts that relate to bnAb induction. Due to the comprehensive data sets available through the Swiss 4.5K Screen several of the topics we will investigate can be systematically addressed for the first time. To define how bnAbs can be best identified and what factors are linked with their induction, we will engage in a series of combined experimental and mathematical analyses to explore improved ways for delineating bnAb responses in polyclonal plasma and defining strategies that allow reliable and ideally also early detection of neutralization breadth development. The latter will be particularly useful for forthcoming vaccine efficacy testing. We will conduct a detailed analysis of HIV-1 binding antibody patterns in order to define antibody signatures that may be linked with bnAb appearance and to probe the influence of the host genome and other viral, disease and host factors on bnAb induction.The Swiss 4.5K Screen identified 239 bnAb inducers - the largest cohort of bnAb inducers thus far. Amongst these individuals we identified several patient groups of high interest including transmission pairs, viral load controllers and superinfection cases. Studying bnAb evolution in these patient groups bears unique potential to understand drivers and consequences of bnAb induction and evolution. Concentrating on the analysis of the virus envelope (Env) in the same set of bnAb inducer patients we aim to unravel how Envs from different subtypes steer bnAb specificity by conducting a comprehensive genotypic and phenotypic characterization of bnAb inducer Envs aiming to define Env features that trigger specificity. A second emphasis will lie on the investigation of bnAb transmission pairs to potentially derive what we refer to as bnAb imprinter Env - an Env that bears the capacity to mount the same bnAb response across individuals.