Multimerization of Ebola GPΔmucin on protein nanoparticle vaccines has minimal effect on elicitation of neutralizing antibodies

Powell, Abigail E.; Xu, Duo; Roth, Gillie A.; Zhang, Kaiming; Chiu, Wah; Appel, Eric A.; Kim, Peter S.

doi:10.3389/fimmu.2022.942897

Multimerization of Ebola GPΔmucin on protein nanoparticle vaccines has minimal effect on elicitation of neutralizing antibodies

Journal Article · Wed Aug 24 00:00:00 EDT 2022 · Frontiers in Immunology

DOI:https://doi.org/10.3389/fimmu.2022.942897· OSTI ID:2471720

Powell, Abigail E. ^[1]; Xu, Duo ^[1]; Roth, Gillie A. ^[1]; Zhang, Kaiming ^[1]; Chiu, Wah ^[2]; Appel, Eric A. ^[1]; Kim, Peter S. ^[3]

Stanford University, CA (United States)
Stanford University, CA (United States); Chan Zuckerberg Biohub, San Francisco, CA (United States) ; SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
Stanford University, CA (United States); Chan Zuckerberg Biohub, San Francisco, CA (United States); SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)

Ebola virus (EBOV), a member of the Filoviridae family of viruses and a causative agent of Ebola Virus Disease (EVD), is a highly pathogenic virus that has caused over twenty outbreaks in Central and West Africa since its formal discovery in 1976. The only FDA-licensed vaccine against Ebola virus, rVSV-ZEBOV-GP (Ervebo®), is efficacious against infection following just one dose. However, since this vaccine contains a replicating virus, it requires ultra-low temperature storage which imparts considerable logistical challenges for distribution and access. Additional vaccine candidates could provide expanded protection to mitigate current and future outbreaks. Here, we designed and characterized two multimeric protein nanoparticle subunit vaccines displaying 8 or 20 copies of GPΔmucin, a truncated form of the EBOV surface protein GP. Single-dose immunization of mice with GPΔmucin nanoparticles revealed that neutralizing antibody levels were roughly equivalent to those observed in mice immunized with non-multimerized GPΔmucin trimers. These results suggest that some protein subunit antigens do not elicit enhanced antibody responses when displayed on multivalent scaffolds and can inform next-generation design of stable Ebola virus vaccine candidates.

View Accepted Manuscript (DOE)

Research Organization:: SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 2471720

Journal Information:: Frontiers in Immunology, Journal Name: Frontiers in Immunology Vol. 13; ISSN 1664-3224

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

References (45)

Modern Subunit Vaccines: Development, Components, and Research Opportunities Moyle, Peter Michael; Toth, Istvan ChemMedChem, Vol. 8, Issue 3 https://doi.org/10.1002/cmdc.201200487	journal	January 2013
Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial Henao-Restrepo, Ana Maria; Longini, Ira M.; Egger, Matthias The Lancet, Vol. 386, Issue 9996 https://doi.org/10.1016/S0140-6736(15)61117-5	journal	August 2015
Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!) Henao-Restrepo, Ana Maria; Camacho, Anton; Longini, Ira M. The Lancet, Vol. 389, Issue 10068 https://doi.org/10.1016/S0140-6736(16)32621-6	journal	February 2017
Safety and immunogenicity of a two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Europe (EBOVAC2): a randomised, observer-blind, participant-blind, placebo-controlled, phase 2 trial Pollard, Andrew J.; Launay, Odile; Lelievre, Jean-Daniel The Lancet Infectious Diseases, Vol. 21, Issue 4 https://doi.org/10.1016/S1473-3099(20)30476-X	journal	April 2021
Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site Kanekiyo, Masaru; Bu, Wei; Joyce, M. Gordon Cell, Vol. 162, Issue 5 https://doi.org/10.1016/j.cell.2015.07.043	journal	August 2015
Ebola Viral Glycoprotein Bound to Its Endosomal Receptor Niemann-Pick C1 Wang, Han; Shi, Yi; Song, Jian Cell, Vol. 164, Issue 1-2 https://doi.org/10.1016/j.cell.2015.12.044	journal	January 2016
Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses Wec, Anna Z.; Herbert, Andrew S.; Murin, Charles D. Cell, Vol. 169, Issue 5 https://doi.org/10.1016/j.cell.2017.04.037	journal	May 2017
Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection Saphire, Erica Ollmann; Schendel, Sharon L.; Fusco, Marnie L. Cell, Vol. 174, Issue 4 https://doi.org/10.1016/j.cell.2018.07.033	journal	August 2018
Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology Piccoli, Luca; Park, Young-Jun; Tortorici, M. Alejandra Cell, Vol. 183, Issue 4 https://doi.org/10.1016/j.cell.2020.09.037	journal	November 2020
Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 Walls, Alexandra C.; Fiala, Brooke; Schäfer, Alexandra Cell, Vol. 183, Issue 5 https://doi.org/10.1016/j.cell.2020.10.043	journal	November 2020
Ebola virus disease: current vaccine solutions Tomori, Oyewale; Kolawole, Matthew Olatunji Current Opinion in Immunology, Vol. 71 https://doi.org/10.1016/j.coi.2021.03.008	journal	August 2021
Stability and suitability for storage and distribution of Ad26.ZEBOV/MVA-BN®-Filo heterologous prime-boost Ebola vaccine Capelle, Martinus A. H.; Babich, Lara; van Deventer-Troost, J. P. Els European Journal of Pharmaceutics and Biopharmaceutics, Vol. 129 https://doi.org/10.1016/j.ejpb.2018.06.001	journal	August 2018
High degree of correlation between Ebola virus BSL-4 neutralization assays and pseudotyped VSV BSL-2 fluorescence reduction neutralization test Konduru, Krishnamurthy; Shurtleff, Amy C.; Bavari, Sina Journal of Virological Methods, Vol. 254 https://doi.org/10.1016/j.jviromet.2018.01.003	journal	April 2018
Vaccine Adjuvant Systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T cell responses against hepatitis B surface antigen in healthy adult volunteers Vandepapelière, Pierre; Horsmans, Yves; Moris, Philippe Vaccine, Vol. 26, Issue 10 https://doi.org/10.1016/j.vaccine.2007.12.038	journal	March 2008
Vaccine Adjuvant Systems containing monophosphoryl lipid A and QS-21 induce strong humoral and cellular immune responses against hepatitis B surface antigen which persist for at least 4 years after vaccination Leroux-Roels, Geert; Van Belle, Pascale; Vandepapeliere, Pierre Vaccine, Vol. 33, Issue 8 https://doi.org/10.1016/j.vaccine.2014.10.078	journal	February 2015
Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice Bengtsson, Karin Lövgren; Song, Haifeng; Stertman, Linda Vaccine, Vol. 34, Issue 16 https://doi.org/10.1016/j.vaccine.2016.02.033	journal	April 2016
A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice Powell, Abigail E.; Zhang, Kaiming; Sanyal, Mrinmoy ACS Central Science, Vol. 7, Issue 1 https://doi.org/10.1021/acscentsci.0c01405	journal	January 2021
Multilamellar Vaccine Particle Elicits Potent Immune Activation with Protein Antigens and Protects Mice against Ebola Virus Infection Fan, Yuchen; Stronsky, Sabrina M.; Xu, Yao ACS Nano, Vol. 13, Issue 10 https://doi.org/10.1021/acsnano.9b03660	journal	September 2019
Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor Lee, Jeffrey E.; Fusco, Marnie L.; Hessell, Ann J. Nature, Vol. 454, Issue 7201 https://doi.org/10.1038/nature07082	journal	July 2008
Ebola virus entry requires the cholesterol transporter Niemann–Pick C1 Carette, Jan E.; Raaben, Matthijs; Wong, Anthony C. Nature, Vol. 477, Issue 7364 https://doi.org/10.1038/nature10348	journal	August 2011
Small molecule inhibitors reveal Niemann–Pick C1 is essential for Ebola virus infection Côté, Marceline; Misasi, John; Ren, Tao Nature, Vol. 477, Issue 7364 https://doi.org/10.1038/nature10380	journal	August 2011
Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies Kanekiyo, Masaru; Wei, Chih-Jen; Yassine, Hadi M. Nature, Vol. 499, Issue 7456 https://doi.org/10.1038/nature12202	journal	May 2013
Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles He, Linling; de Val, Natalia; Morris, Charles D. Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms12041	journal	June 2016
Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses Jones, Steven M.; Feldmann, Heinz; Ströher, Ute Nature Medicine, Vol. 11, Issue 7 https://doi.org/10.1038/nm1258	journal	June 2005
Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines He, Linling; Chaudhary, Anshul; Lin, Xiaohe Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-22867-w	journal	May 2021
COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses Sahin, Ugur; Muik, Alexander; Derhovanessian, Evelyna Nature, Vol. 586, Issue 7830 https://doi.org/10.1038/s41586-020-2814-7	journal	September 2020
Ebola Feldmann, Heinz; Sprecher, Armand; Geisbert, Thomas W. New England Journal of Medicine, Vol. 382, Issue 19 https://doi.org/10.1056/NEJMra1901594	journal	May 2020
Processing of the Ebola virus glycoprotein by the proprotein convertase furin Volchkov, V. E.; Feldmann, H.; Volchkova, V. A. Proceedings of the National Academy of Sciences, Vol. 95, Issue 10 https://doi.org/10.1073/pnas.95.10.5762	journal	May 1998
Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9-A resolution Malashkevich, V. N.; Schneider, B. J.; McNally, M. L. Proceedings of the National Academy of Sciences, Vol. 96, Issue 6 https://doi.org/10.1073/pnas.96.6.2662	journal	March 1999
Identification of QS-21 as an Inflammasome-activating Molecular Component of Saponin Adjuvants Marty-Roix, Robyn; Vladimer, Gregory I.; Pouliot, Kimberly Journal of Biological Chemistry, Vol. 291, Issue 3 https://doi.org/10.1074/jbc.M115.683011	journal	January 2016
Mechanistic understanding of N-glycosylation in Ebola virus glycoprotein maturation and function Wang, Bin; Wang, Yujie; Frabutt, Dylan A. Journal of Biological Chemistry, Vol. 292, Issue 14 https://doi.org/10.1074/jbc.M116.768168	journal	April 2017
Stability of a Vesicular Stomatitis Virus–Vectored Ebola Vaccine Arnemo, Marianne; Viksmoen Watle, Sara Sofie; Schoultz, Kristin Merete Journal of Infectious Diseases, Vol. 213, Issue 6 https://doi.org/10.1093/infdis/jiv532	journal	November 2015
Endosomal Proteolysis of the Ebola Virus Glycoprotein Is Necessary for Infection Chandran, K. Science, Vol. 308, Issue 5728 https://doi.org/10.1126/science.1110656	journal	June 2005
Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody Corti, D.; Misasi, J.; Mulangu, S. Science, Vol. 351, Issue 6279 https://doi.org/10.1126/science.aad5224	journal	February 2016
Isolation of potent neutralizing antibodies from a survivor of the 2014 Ebola virus outbreak Bornholdt, Z. A.; Turner, H. L.; Murin, C. D. Science, Vol. 351, Issue 6277 https://doi.org/10.1126/science.aad5788	journal	February 2016
Structural and molecular basis for Ebola virus neutralization by protective human antibodies Misasi, J.; Gilman, M. S. A.; Kanekiyo, M. Science, Vol. 351, Issue 6279 https://doi.org/10.1126/science.aad6117	journal	February 2016
Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability Brouwer, Philip J. M.; Caniels, Tom G.; van der Straten, Karlijn Science, Vol. 369, Issue 6504 https://doi.org/10.1126/science.abc5902	journal	June 2020
Covalent Modifications of the Ebola Virus Glycoprotein Jeffers, S. A.; Sanders, D. A.; Sanchez, A. Journal of Virology, Vol. 76, Issue 24 https://doi.org/10.1128/jvi.76.24.12463-12472.2002	journal	December 2002
Role of Endosomal Cathepsins in Entry Mediated by the Ebola Virus Glycoprotein Schornberg, K.; Matsuyama, S.; Kabsch, K. Journal of Virology, Vol. 80, Issue 8 https://doi.org/10.1128/jvi.80.8.4174-4178.2006	journal	March 2006
Comprehensive Functional Analysis of N-Linked Glycans on Ebola Virus GP1 Lennemann, Nicholas J.; Rhein, Bethany A.; Ndungo, Esther mBio, Vol. 5, Issue 1 https://doi.org/10.1128/mBio.00862-13	journal	January 2014
Ebola: Lessons on Vaccine Development Feldmann, Heinz; Feldmann, Friederike; Marzi, Andrea Annual Review of Microbiology, Vol. 72, Issue 1 https://doi.org/10.1146/annurev-micro-090817-062414	journal	September 2018
Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge Konduru, Krishnamurthy; Shurtleff, Amy C.; Bradfute, Steven B. PLOS ONE, Vol. 11, Issue 9 https://doi.org/10.1371/journal.pone.0162446	journal	September 2016
A prophylactic multivalent vaccine against different filovirus species is immunogenic and provides protection from lethal infections with Ebolavirus and Marburgvirus species in non-human primates Callendret, Benoit; Vellinga, Jort; Wunderlich, Kerstin PLOS ONE, Vol. 13, Issue 2 https://doi.org/10.1371/journal.pone.0192312	journal	February 2018
Protocol and Reagents for Pseudotyping Lentiviral Particles with SARS-CoV-2 Spike Protein for Neutralization Assays Crawford, Katharine H. D.; Eguia, Rachel; Dingens, Adam S. Viruses, Vol. 12, Issue 5 https://doi.org/10.3390/v12050513	journal	May 2020
Recurrent Ebolavirus disease in the Democratic Republic of Congo: update and challenges Inungu, Joseph; Iheduru-Anderson, Kechi AIMS Public Health, Vol. 6, Issue 4 https://doi.org/10.3934/publichealth.2019.4.502	journal	January 2019

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60 APPLIED LIFE SCIENCES
GPDmucin
Immunology
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glycoprotein
protein nanoparticles
subunit vaccine

Multimerization of Ebola GPΔmucin on protein nanoparticle vaccines has minimal effect on elicitation of neutralizing antibodies

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