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Gunn, Bronwyn

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Gunn

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Bronwyn

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Gunn, Bronwyn
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    Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs
    (American Society for Microbiology, 2018) Bricault, Christine; Kovacs, James M.; Badamchi-Zadeh, Alexander; McKee, Krisha; Shields, Jennifer L.; Gunn, Bronwyn; Neubauer, George H.; Ghantous, Fadi; Jennings, Julia; Gillis, Lindsey; Perry, James; Nkolola, Joseph; Alter, Galit; Chen, Bing; Stephenson, Kathryn; Doria-Rose, Nicole; Mascola, John R.; Seaman, Michael; Barouch, Dan
    ABSTRACT A vaccination regimen capable of eliciting potent and broadly neutralizing antibodies (bNAbs) remains an unachieved goal of the HIV-1 vaccine field. Here, we report the immunogenicity of longitudinal prime/boost vaccination regimens with a panel of HIV-1 envelope (Env) gp140 protein immunogens over a period of 200 weeks in guinea pigs. We assessed vaccine regimens that included a monovalent clade C gp140 (C97ZA012 [C97]), a tetravalent regimen consisting of four clade C gp140s (C97ZA012, 459C, 405C, and 939C [4C]), and a tetravalent regimen consisting of clade A, B, C, and mosaic gp140s (92UG037, PVO.4, C97ZA012, and Mosaic 3.1, respectively [ABCM]). We found that the 4C and ABCM prime/boost regimens were capable of eliciting greater magnitude and breadth of binding antibody responses targeting variable loop 2 (V2) over time than the monovalent C97-only regimen. The longitudinal boosting regimen conducted over more than 2 years increased the magnitude of certain tier 1 NAb responses but did not increase the magnitude or breadth of heterologous tier 2 NAb responses. These data suggest that additional immunogen design strategies are needed to induce broad, high-titer tier 2 NAb responses. IMPORTANCE: The elicitation of potent, broadly neutralizing antibodies (bNAbs) remains an elusive goal for the HIV-1 vaccine field. In this study, we explored the use of a long-term vaccination regimen with different immunogens to determine if we could elicit bNAbs in guinea pigs. We found that longitudinal boosting over more than 2 years increased tier 1 NAb responses but did not increase the magnitude and breadth of tier 2 NAb responses. These data suggest that additional immunogen designs and vaccination strategies will be necessary to induce broad tier 2 NAb responses.
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    Exploiting glycan topography for computational design of Env glycoprotein antigenicity
    (Public Library of Science, 2018) Yu, Wen-Han; Zhao, Peng; Draghi, Monia; Arevalo, Claudia; Karsten, Christina; Suscovich, Todd J.; Gunn, Bronwyn; Streeck, Hendrik; Brass, Abraham L.; Tiemeyer, Michael; Seaman, Michael; Mascola, John R.; Wells, Lance; Lauffenburger, Douglas A.; Alter, Galit
    Mounting evidence suggests that glycans, rather than merely serving as a “shield”, contribute critically to antigenicity of the HIV envelope (Env) glycoprotein, representing critical antigenic determinants for many broadly neutralizing antibodies (bNAbs). While many studies have focused on defining the role of individual glycans or groups of proximal glycans in bNAb binding, little is known about the effects of changes in the overall glycan landscape in modulating antibody access and Env antigenicity. Here we developed a systems glycobiology approach to reverse engineer the complexity of HIV glycan heterogeneity to guide antigenicity-based de novo glycoprotein design. bNAb binding was assessed against a panel of 94 recombinant gp120 monomers exhibiting defined glycan site occupancies. Using a Bayesian machine learning algorithm, bNAb-specific glycan footprints were identified and used to design antigens that selectively alter bNAb antigenicity as a proof-of concept. Our approach provides a new design strategy to predictively modulate antigenicity via the alteration of glycan topography, thereby focusing the humoral immune response on sites of viral vulnerability for HIV.