title: Evolution of B cell analysis and Env trimer redesign.
abstract: HIV-1 and its surface envelope glycoproteins (Env), gp120 and gp41, have evolved immune evasion strategies that render the elicitation of effective antibody responses to the functional Env entry unit extremely difficult. HIV-1 establishes chronic infection and stimulates vigorous immune responses in the human host; forcing selection of viral variants that escape cellular and antibody (Ab)-mediated immune pressure, yet possess contemporary fitness. Successful survival of fit variants through the gauntlet of the human immune system make this virus and these glycoproteins a formidable challenge to target by vaccination, requiring a systematic approach to Env mimetic immunogen design and evaluation of elicited responses. Here, we review key aspects of HIV-1 Env immunogenicity and immunogen re-design, based on experimental data generated by us and others over the past decade or more. We further provide rationale and details regarding the use of newly evolving tools to analyze B cell responses, including approaches to use next generation sequencing for antibody lineage tracing and B cell fate mapping. Together, these developments offer opportunities to address long-standing questions about the establishment of effective B cell immunity elicited by vaccination, not just against HIV-1.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Karlsson Hedestam
authors.affiliation: Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center at TSRI, La Jolla, CA, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Guenaga
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Corcoran
authors.affiliation: Department of Immunology and Microbial Science, IAVI Neutralizing Antibody Center at TSRI, La Jolla, CA, USA.|The Scripps CHAVI-ID, La Jolla, CA, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Wyatt
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D005075:Biological Evolution; D032701:Biomimetics; D002454:Cell Differentiation; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D057131:Immune Evasion; D056724:Immunity, Humoral; D007118:Immunoassay
chemical_list: D016915:AIDS Vaccines; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41
keywords:  HIV-1;  epitope;  repertoire;  vaccine; B cell; antibody