Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses

Kassardjian, Audrey; Sun, Eric; Sookhoo, Jamie; Muthuraman, Krithika; Boligan, Kayluz Frias; Kucharska, Iga; Rujas, Edurne; Jetha, Arif; Branch, Donald R.; Babiuk, Shawn; Barber, Brian; Julien, Jean-Philippe

doi:10.1016/j.celrep.2023.112391

Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses

Journal Article · Mon Apr 03 00:00:00 EDT 2023 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2023.112391· OSTI ID:2423518

Kassardjian, Audrey ^[1]; Sun, Eric ^[1]; Sookhoo, Jamie ^[2]; Muthuraman, Krithika ^[1]; Boligan, Kayluz Frias ^[3]; Kucharska, Iga ^[4]; Rujas, Edurne ^[5]; Jetha, Arif ^[4]; Branch, Donald R. ^[6]; Babiuk, Shawn ^[2]; Barber, Brian ^[7]; ^[1]

The Hospital for Sick Children Research Institute, Toronto, ON (Canada); University of Toronto, ON (Canada)
National Centre for Foreign Animal Disease, Winnipeg, MB (Canada); University of Manitoba, Winnipeg, MB (Canada)
Keenan Research Centre, Toronto, ON (Canada)
The Hospital for Sick Children Research Institute, Toronto, ON (Canada)
The Hospital for Sick Children Research Institute, Toronto, ON (Canada); Basque Foundation for Science, Bilbao (Spain); University of the Basque Country UPV/EHU, Vitoria (Spain); Bioaraba, Microbiology, Infectious Disease, Antimicrobial Agents, and Gene Therapy, Vitoria (Spain)
Keenan Research Centre, Toronto, ON (Canada); University of Toronto, ON (Canada)
University of Toronto, ON (Canada)

Subunit vaccines typically require co-administration with an adjuvant to elicit protective immunity, adding development hurdles that can impede rapid pandemic responses. To circumvent the need for adjuvant in a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine, we engineer a thermostable immunotargeting vaccine (ITV) that leverages the pan-HLA-DR monoclonal antibody 44H10 to deliver the viral spike protein receptor-binding domain (RBD) to antigen-presenting cells. X-ray crystallography shows that 44H10 binds to a conserved epitope on HLA-DR, providing the basis for its broad HLA-DR reactivity. Adjuvant-free ITV immunization in rabbits and ferrets induces robust anti-RBD antibody responses that neutralize SARS-CoV-2 variants of concern and protect recipients from SARS-CoV-2 challenge. We demonstrate that the modular nature of the ITV scaffold with respect to helper T cell epitopes and diverse RBD antigens facilitates broad sarbecovirus neutralization. Our findings support anti-HLA-DR immunotargeting as an effective means to induce strong antibody responses to subunit antigens without requiring an adjuvant.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: European Union’s Horizon 2020 research and innovation program; Hospital for Sick Children Foundation; National Cancer Institute; National Institute of General Medical Sciences; National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2423518

Journal Information:: Cell Reports, Journal Name: Cell Reports Journal Issue: 4 Vol. 42; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

References (74)

Duration of Immunity and Effectiveness of Diphtheria-Tetanus–Acellular Pertussis Vaccines in Children Domenech de Cellès, Matthieu; Rohani, Pejman; King, Aaron A. JAMA Pediatrics, Vol. 173, Issue 6 https://doi.org/10.1001/jamapediatrics.2019.0711	journal	June 2019
Development of Receptor Binding Domain (RBD)‐Conjugated Nanoparticle Vaccines with Broad Neutralization against SARS‐CoV‐2 Delta and Other Variants Chen, Ran; Zhang, Xiantao; Yuan, Yaochang Advanced Science, Vol. 9, Issue 11 https://doi.org/10.1002/advs.202105378	journal	February 2022
The emergence of Omicron lineages BA.4 and BA.5, and the global spreading trend Desingu, Perumal A.; Nagarajan, Kumaresan Journal of Medical Virology, Vol. 94, Issue 11 https://doi.org/10.1002/jmv.27967	journal	July 2022
The immunotargeting approach to adjuvant-independent subunit vaccine design Barber, Brian H. Seminars in Immunology, Vol. 9, Issue 5 https://doi.org/10.1006/smim.1997.0085	journal	October 1997
Usos Industriales y Abastecimiento Sustenable de Saponina de Quillaja saponaria Martín, Ricardo San; Briones, Reinaldo Economic Botany, Vol. 53, Issue 3 https://doi.org/10.1007/BF02866642	journal	July 1999
Comparative Safety of Vaccine Adjuvants: A Summary of Current Evidence and Future Needs Petrovsky, Nikolai Drug Safety, Vol. 38, Issue 11 https://doi.org/10.1007/s40264-015-0350-4	journal	October 2015
Cross-reaction of a monoclonal antibody to human MHC class II molecules with rabbit B cells Dubiski, S.; Cinader, B.; chou, C. -T. Molecular Immunology, Vol. 25, Issue 8 https://doi.org/10.1016/0161-5890(88)90107-1	journal	August 1988
Characterization of the adjuvant-free serological response to protein antigens coupled to antibodies specific for class II MHC determinants Carayanniotis, George; Barber, Brian H. Vaccine, Vol. 8, Issue 2 https://doi.org/10.1016/0264-410X(90)90136-A	journal	April 1990
The immunotargeting approach to adjuvant-independent immunization with influenza haemagglutinin Skea, D. L.; Douglas, A. R.; Skehel, J. J. Vaccine, Vol. 11, Issue 10 https://doi.org/10.1016/0264-410X(93)90123-F	journal	January 1993
Closing the global vaccine equity gap: equitably distributed manufacturing Dzau, Victor J.; Balatbat, Celynne A.; Offodile, Anaeze C. The Lancet, Vol. 399, Issue 10339 https://doi.org/10.1016/S0140-6736(22)00793-0	journal	May 2022
Pan DR binding sequence provides T-cell help for induction of protective antibodies against Plasmodium yoelii sporozoites Franke, Eileen D.; Hoffman, Stephen L.; Sacci, John B. Vaccine, Vol. 17, Issue 9-10 https://doi.org/10.1016/S0264-410X(98)00341-7	journal	March 1999
Neutralization of SARS-CoV-2 Omicron sub-lineages BA.1, BA.1.1, and BA.2 Evans, John P.; Zeng, Cong; Qu, Panke Cell Host & Microbe, Vol. 30, Issue 8 https://doi.org/10.1016/j.chom.2022.04.014	journal	August 2022
Nanoparticle Vaccines Based on the Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust Protective Immune Responses Ma, Xiancai; Zou, Fan; Yu, Fei Immunity, Vol. 53, Issue 6 https://doi.org/10.1016/j.immuni.2020.11.015	journal	December 2020
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
RELION: Implementation of a Bayesian approach to cryo-EM structure determination Scheres, Sjors H. W. Journal of Structural Biology, Vol. 180, Issue 3, p. 519-530 https://doi.org/10.1016/j.jsb.2012.09.006	journal	December 2012
Conformational constraints imposed on a pan-neutralizing HIV-1 antibody epitope result in increased antigenicity but not neutralizing response Ho, Jason; Uger, Robert A.; Zwick, Michael B. Vaccine, Vol. 23, Issue 13 https://doi.org/10.1016/j.vaccine.2004.09.037	journal	February 2005
Reactogenicity and immunogenicity of an inactivated influenza vaccine administered by intramuscular or subcutaneous injection in elderly adults Cook, Ian F.; Barr, Ian; Hartel, Gunter Vaccine, Vol. 24, Issue 13 https://doi.org/10.1016/j.vaccine.2005.11.057	journal	March 2006
Generation of a universal CD4 memory T cell recall peptide effective in humans, mice and non-human primates Fraser, Christopher C.; H. Altreuter, David; Ilyinskii, Petr Vaccine, Vol. 32, Issue 24 https://doi.org/10.1016/j.vaccine.2014.02.024	journal	May 2014
Enhanced elicitation of potent neutralizing antibodies by the SARS-CoV-2 spike receptor binding domain Fc fusion protein in mice Liu, Xianglei; Drelich, Aleksandra; Li, Wei Vaccine, Vol. 38, Issue 46 https://doi.org/10.1016/j.vaccine.2020.09.058	journal	October 2020
Overview of global regulatory toxicology requirements for vaccines and adjuvants Sun, Yuansheng; Gruber, Marion; Matsumoto, Mineo Journal of Pharmacological and Toxicological Methods, Vol. 65, Issue 2 https://doi.org/10.1016/j.vascn.2012.01.002	journal	March 2012
Adjuvant-free IgG responses induced with antigen coupled to antibodies against class II MHC Carayanniotis, George; Barber, Brian H. Nature, Vol. 327, Issue 6117 https://doi.org/10.1038/327059a0	journal	May 1987
The HLA genomic loci map: expression, interaction, diversity and disease Shiina, Takashi; Hosomichi, Kazuyoshi; Inoko, Hidetoshi Journal of Human Genetics, Vol. 54, Issue 1 https://doi.org/10.1038/jhg.2008.5	journal	January 2009
Immunological mechanisms of vaccination Pulendran, Bali; Ahmed, Rafi Nature Immunology, Vol. 12, Issue 6 https://doi.org/10.1038/ni.2039	journal	May 2011
The self-assembled nanoparticle-based trimeric RBD mRNA vaccine elicits robust and durable protective immunity against SARS-CoV-2 in mice Sun, Wenqiang; He, Lihong; Zhang, He Signal Transduction and Targeted Therapy, Vol. 6, Issue 1 https://doi.org/10.1038/s41392-021-00750-w	journal	September 2021
Ferritin nanoparticle-based SARS-CoV-2 RBD vaccine induces a persistent antibody response and long-term memory in mice Wang, Wenjun; Huang, Baoying; Zhu, Yanping Cellular & Molecular Immunology, Vol. 18, Issue 3 https://doi.org/10.1038/s41423-021-00643-6	journal	February 2021
Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers Rujas, Edurne; Kucharska, Iga; Tan, Yong Zi Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-23825-2	journal	June 2021
Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques Marlin, Romain; Godot, Veronique; Cardinaud, Sylvain Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-25382-0	journal	September 2021
Enhancing vaccine antibody responses by targeting Clec9A on dendritic cells Park, Hae-Young; Tan, Peck S.; Kavishna, Ranmali npj Vaccines, Vol. 2, Issue 1 https://doi.org/10.1038/s41541-017-0033-5	journal	November 2017
Enhanced germinal center reaction by targeting vaccine antigen to major histocompatibility complex class II molecules Andersen, Tor Kristian; Huszthy, Peter C.; Gopalakrishnan, Ramakrishna P. npj Vaccines, Vol. 4, Issue 1 https://doi.org/10.1038/s41541-019-0101-0	journal	February 2019
Emerging concepts in the science of vaccine adjuvants Pulendran, Bali; S. Arunachalam, Prabhu; O’Hagan, Derek T. Nature Reviews Drug Discovery, Vol. 20, Issue 6 https://doi.org/10.1038/s41573-021-00163-y	journal	April 2021
Potently neutralizing and protective human antibodies against SARS-CoV-2 Zost, Seth J.; Gilchuk, Pavlo; Case, James Brett Nature, Vol. 584, Issue 7821 https://doi.org/10.1038/s41586-020-2548-6	journal	July 2020
Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike Liu, Lihong; Wang, Pengfei; Nair, Manoj S. Nature, Vol. 584, Issue 7821 https://doi.org/10.1038/s41586-020-2571-7	journal	July 2020
SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies Barnes, Christopher O.; Jette, Claudia A.; Abernathy, Morgan E. Nature, Vol. 588, Issue 7839 https://doi.org/10.1038/s41586-020-2852-1	journal	October 2020
Antibody evasion properties of SARS-CoV-2 Omicron sublineages Iketani, Sho; Liu, Lihong; Guo, Yicheng Nature, Vol. 604, Issue 7906 https://doi.org/10.1038/s41586-022-04594-4	journal	March 2022
A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2–spike protein–protein interaction Tan, Chee Wah; Chia, Wan Ni; Qin, Xijian Nature Biotechnology, Vol. 38, Issue 9 https://doi.org/10.1038/s41587-020-0631-z	journal	July 2020
Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies Bruel, Timothée; Hadjadj, Jérôme; Maes, Piet Nature Medicine, Vol. 28, Issue 6 https://doi.org/10.1038/s41591-022-01792-5	journal	March 2022
Antibody-targeted vaccines Keler, T.; He, L.; Ramakrishna, V. Oncogene, Vol. 26, Issue 25 https://doi.org/10.1038/sj.onc.1210375	journal	May 2007
Efficacy of Antiviral Agents against the SARS-CoV-2 Omicron Subvariant BA.2 Takashita, Emi; Kinoshita, Noriko; Yamayoshi, Seiya New England Journal of Medicine, Vol. 386, Issue 15 https://doi.org/10.1056/NEJMc2201933	journal	April 2022
Addressing Vaccine Inequity — Covid-19 Vaccines as a Global Public Good Hunter, David J.; Abdool Karim, Salim S.; Baden, Lindsey R. New England Journal of Medicine, Vol. 386, Issue 12 https://doi.org/10.1056/NEJMe2202547	journal	March 2022
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine Polack, Fernando P.; Thomas, Stephen J.; Kitchin, Nicholas New England Journal of Medicine, Vol. 383, Issue 27 https://doi.org/10.1056/NEJMoa2034577	journal	December 2020
Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine Baden, Lindsey R.; El Sahly, Hana M.; Essink, Brandon New England Journal of Medicine, Vol. 384, Issue 5 https://doi.org/10.1056/NEJMoa2035389	journal	February 2021
A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants Pishesha, Novalia; Harmand, Thibault J.; Rothlauf, Paul W. Proceedings of the National Academy of Sciences, Vol. 118, Issue 44 https://doi.org/10.1073/pnas.2116147118	journal	October 2021
Structure of Severe Acute Respiratory Syndrome Coronavirus Receptor-binding Domain Complexed with Neutralizing Antibody Prabakaran, Ponraj; Gan, Jianhua; Feng, Yang Journal of Biological Chemistry, Vol. 281, Issue 23 https://doi.org/10.1074/jbc.M600697200	journal	April 2006
Structural Basis of Neutralization by a Human Anti-severe Acute Respiratory Syndrome Spike Protein Antibody, 80R Hwang, William C.; Lin, Yaqiong; Santelli, Eugenio Journal of Biological Chemistry, Vol. 281, Issue 45 https://doi.org/10.1074/jbc.M603275200	journal	September 2006
Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody Tian, Xiaolong; Li, Cheng; Huang, Ailing Emerging Microbes & Infections, Vol. 9, Issue 1 https://doi.org/10.1080/22221751.2020.1729069	journal	January 2020
Enhanced antigen immunogenicity induced by bispecific antibodies. Snider, D. P.; Kaubisch, A.; Segal, D. M. The Journal of experimental medicine, Vol. 171, Issue 6 https://doi.org/10.1084/jem.171.6.1957	journal	June 1990
A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis Scally, Stephen W.; Petersen, Jan; Law, Soi Cheng Journal of Experimental Medicine, Vol. 210, Issue 12 https://doi.org/10.1084/jem.20131241	journal	November 2013
Durability of Vaccine-Induced Immunity Against Tetanus and Diphtheria Toxins: A Cross-sectional Analysis Hammarlund, Erika; Thomas, Archana; Poore, Elizabeth A. Clinical Infectious Diseases, Vol. 62, Issue 9 https://doi.org/10.1093/cid/ciw066	journal	March 2016
WebLogo: A Sequence Logo Generator Crooks, Gavin E.; Hon, Gary; Chandonia, John-Marc Genome Research, Vol. 14, Issue 6, p. 1188-1190 https://doi.org/10.1101/gr.849004	journal	May 2004
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
PHENIX: a comprehensive Python-based system for macromolecular structure solution Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221 https://doi.org/10.1107/S0907444909052925	journal	January 2010
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV Yuan, Meng; Wu, Nicholas C.; Zhu, Xueyong Science, Vol. 368, Issue 6491 https://doi.org/10.1126/science.abb7269	journal	April 2020
Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail Hansen, Johanna; Baum, Alina; Pascal, Kristen E. Science https://doi.org/10.1126/science.abd0827	journal	June 2020
Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies Baum, Alina; Fulton, Benjamin O.; Wloga, Elzbieta Science https://doi.org/10.1126/science.abd0831	journal	June 2020
Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice Cohen, Alexander A.; Gnanapragasam, Priyanthi N. P.; Lee, Yu E. Science, Vol. 371, Issue 6530 https://doi.org/10.1126/science.abf6840	journal	February 2021
Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine–elicited human sera Muik, Alexander; Lui, Bonny Gaby; Wallisch, Ann-Kathrin Science, Vol. 375, Issue 6581 https://doi.org/10.1126/science.abn7591	journal	February 2022
Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses Mao, Tianyang; Israelow, Benjamin; Peña-Hernández, Mario A. Science, Vol. 378, Issue 6622 https://doi.org/10.1126/science.abo2523	journal	November 2022
Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models Cohen, Alexander A.; van Doremalen, Neeltje; Greaney, Allison J. Science, Vol. 377, Issue 6606 https://doi.org/10.1126/science.abq0839	journal	August 2022
Antigenic cartography of SARS-CoV-2 reveals that Omicron BA.1 and BA.2 are antigenically distinct Mykytyn, Anna Z.; Rissmann, Melanie; Kok, Adinda Science Immunology, Vol. 7, Issue 75 https://doi.org/10.1126/sciimmunol.abq4450	journal	September 2022
A simple protein-based surrogate neutralization assay for SARS-CoV-2 Abe, Kento T.; Li, Zhijie; Samson, Reuben JCI Insight, Vol. 5, Issue 19 https://doi.org/10.1172/jci.insight.142362	journal	October 2020
Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR Corman, Victor M.; Landt, Olfert; Kaiser, Marco Eurosurveillance, Vol. 25, Issue 3 https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045	journal	January 2020
A Comparison of Intramuscular and Subcutaneous Administration of LigA Subunit Vaccine Adjuvanted with Neutral Liposomal Formulation Containing Monophosphoryl Lipid A and QS21 Techawiwattanaboon, Teerasit; Barnier-Quer, Christophe; Palaga, Tanapat Vaccines, Vol. 8, Issue 3 https://doi.org/10.3390/vaccines8030494	journal	September 2020
Natural and Synthetic Saponins as Vaccine Adjuvants Wang, Pengfei Vaccines, Vol. 9, Issue 3 https://doi.org/10.3390/vaccines9030222	journal	March 2021
A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response Lainšček, Duško; Fink, Tina; Forstnerič, Vida Vaccines, Vol. 9, Issue 5 https://doi.org/10.3390/vaccines9050431	journal	April 2021
Visualizing Proteins and Macromolecular Complexes by Negative Stain EM: from Grid Preparation to Image Acquisition Booth, David S.; Avila-Sakar, Agustin; Cheng, Yifan Journal of Visualized Experiments, Issue 58 https://doi.org/10.3791/3227-v	journal	December 2011
The Magnitude and IgG Subclass of Antibodies Elicited by Targeted DNA Vaccines Are Influenced by Specificity for APC Surface Molecules Braathen, Ranveig; Spång, Heidi C. L.; Lindeberg, Mona M. ImmunoHorizons, Vol. 2, Issue 1 https://doi.org/10.4049/immunohorizons.1700038	journal	January 2018
Identification of several cell surface proteins of non-T, non-B acute lymphoblastic leukemia by using monoclonal antibodies. Quackenbush, E. J.; Letarte, M. The Journal of Immunology, Vol. 134, Issue 2 https://doi.org/10.4049/jimmunol.134.2.1276	journal	February 1985
Targeted antigen presentation using crosslinked antibody heteroaggregates. Snider, D. P.; Segal, D. M. The Journal of Immunology, Vol. 139, Issue 5 https://doi.org/10.4049/jimmunol.139.5.1609	journal	September 1987
Studies of the adjuvant-independent antibody response to immunotargeting. Target structure dependence, isotype distribution, and induction of long term memory. Skea, D. L.; Barber, B. H. The Journal of Immunology, Vol. 151, Issue 7 https://doi.org/10.4049/jimmunol.151.7.3557	journal	October 1993
Antigen Targeting to Human HLA Class II Molecules Increases Efficacy of DNA Vaccination Grodeland, Gunnveig; Fredriksen, Agnete Brunsvik; Løset, Geir Åge The Journal of Immunology, Vol. 197, Issue 9 https://doi.org/10.4049/jimmunol.1600893	journal	November 2016
Linear PADRE T Helper Epitope and Carbohydrate B Cell Epitope Conjugates Induce Specific High Titer IgG Antibody Responses Alexander, Jeff; del Guercio, Marie-France; Maewal, Ajesh The Journal of Immunology, Vol. 164, Issue 3 https://doi.org/10.4049/jimmunol.164.3.1625	journal	February 2000
Collaboration gets the most out of software Morin, Andrew; Eisenbraun, Ben; Key, Jason eLife, Vol. 2 https://doi.org/10.7554/eLife.01456	journal	September 2013

Similar Records

Neutralizing monoclonal antibodies elicited by mosaic RBD nanoparticles bind conserved sarbecovirus epitopes

Journal Article · Wed Oct 26 20:00:00 EDT 2022 · Immunity · OSTI ID:2006467

Shark nanobodies with potent SARS-CoV-2 neutralizing activity and broad sarbecovirus reactivity

Journal Article · Thu Feb 02 19:00:00 EST 2023 · Nature Communications · OSTI ID:2423606

A TLR7-nanoparticle adjuvant promotes a broad immune response against heterologous strains of influenza and SARS-CoV-2

Journal Article · Sun Jan 29 19:00:00 EST 2023 · Nature Materials · OSTI ID:1923248

Related Subjects

60 APPLIED LIFE SCIENCES
CP: Immunology
MHC class II
SARS-CoV-2
adjuvants
antibodies
cell biology
immunotargeting
vaccines

Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses

Citation Formats

References (74)

Similar Records

Related Subjects