E2 multimeric scaffolds displaying HIV-1 Envelope regions elicit V3 and MPER-specific neutralizing antibody and T cell responses when combined with gp160 plasmid DNA

Abstract

Event Abstract Back to Event E2 multimeric scaffolds displaying HIV-1 Envelope regions elicit V3 and MPER-specific neutralizing antibody and T cell responses when combined with gp160 plasmid DNA Maria Trovato1, Shelly J. Krebs2, Sean McBurney2, Chelsea Smith2, Pablo J. Jaworski2, William F. Sutton2, Rossella Sartorius1, Luciana D'Apice1, Piergiuseppe De Berardinis1 and Nancy L. Haigwood2* 1 Institute of Protein Biochemistry, C.N.R., Italy 2 Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Sciences University, United States It is widely believed that induction of both broadly neutralizing antibodies (bNAbs) and T cells are crucial for a successful HIV-1 vaccine. To elicit immune responses against HIV-1 we generated multimeric scaffolds, based on the E2 component of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus, displaying antigens from the HIV Envelope (Env) glycoproteins gp120 and gp41. E2 self-assembles into a 60-mer particle with 60 copies of an antigen on each scaffold. The HIV-SF162 V3 and MPER regions were expressed as N-terminal fusions to the E2 core. To increase solubility, Env-E2 scaffolds were refolded from inclusion bodies with equimolar amounts of E2wt and purified by size exclusion chromatography. Purified Env-E2 multimers were tested alone or in combination with HIV-SF162 Env(gp160) plasmid DNA in rabbits and mice. We also tested DNA expressing Envelope gp160 with deletions in variable regions V2, V3, and V1-V3. Immunization with V3-E2 co-administered with DNA elicited strong V3-specific NAb response after two immunizations in 6 weeks in rabbits and V3-dextramer specific CD8+ T cells producing IFN-gamma in mice. Rabbits immunized with DNA plus MPER-E2 rapidly generated NAbs targeting the broadly neutralizing 2F5 as well as the 4E10 epitopes, confirmed using HIV-2/MPER chimeric viruses. CD4+ T-cell response and cytokine polarization were also investigated. Rabbits immunized with MPER-E2 had NAbs against both Tier 1 and Tier 2 HIV-viruses. Our results indicate that this novel strategy of co-immunization with E2 scaffolds and DNA could represent an efficient platform by which to direct immune responses, including bNAbs, toward HIV-1 conserved regions. Keywords: HIV, Vaccine, neutralizing antibodies, T cells, Scaffold Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Trovato M, Krebs SJ, McBurney S, Smith C, Jaworski PJ, Sutton WF, Sartorius R, D'Apice L, De Berardinis P and Haigwood NL (2013). E2 multimeric scaffolds displaying HIV-1 Envelope regions elicit V3 and MPER-specific neutralizing antibody and T cell responses when combined with gp160 plasmid DNA. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00891 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 21 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Nancy L Haigwood, Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Sciences University, Beaverton, Oregon, 97006, United States, haigwoon@ohsu.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Maria Trovato Shelly J Krebs Sean McBurney Chelsea Smith Pablo J Jaworski William F Sutton Rossella Sartorius Luciana D'Apice Piergiuseppe De Berardinis Nancy L Haigwood Google Maria Trovato Shelly J Krebs Sean McBurney Chelsea Smith Pablo J Jaworski William F Sutton Rossella Sartorius Luciana D'Apice Piergiuseppe De Berardinis Nancy L Haigwood Google Scholar Maria Trovato Shelly J Krebs Sean McBurney Chelsea Smith Pablo J Jaworski William F Sutton Rossella Sartorius Luciana D'Apice Piergiuseppe De Berardinis Nancy L Haigwood PubMed Maria Trovato Shelly J Krebs Sean McBurney Chelsea Smith Pablo J Jaworski William F Sutton Rossella Sartorius Luciana D'Apice Piergiuseppe De Berardinis Nancy L Haigwood Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.