@article{open2664,
          volume = {6},
          number = {1},
           month = {February},
          author = {Philip J. M. Brouwer and Aleksandar Antanasijevic and Marlon de Gast and Joel D Allen and Tom P. L. Bijl and Anila Yasmeen and Rashmi Ravichandran and Judith A. Burger and Gabriel Ozorowski and Jonathan L. Torres and Celia LaBranche and David C. Montefiori and Rajesh P. Ringe and Marit J. Van Gils and John P. Moore and Per Johan Klasse and Max Crispin and Neil P. King and Andrew B. Ward and Rogier W. Sanders},
            note = {Open Access},
           title = {Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles},
       publisher = {Nature Research},
            year = {2021},
         journal = {NPJ VACCINES},
           pages = {1--24},
        keywords = {Immunology;Research \& Experimental Medicine},
             url = {http://crdd.osdd.net/open/2664/},
        abstract = {The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes.}
}