Safety, immunogenicity, and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman primates.


Journal

Cellular & molecular immunology
ISSN: 2042-0226
Titre abrégé: Cell Mol Immunol
Pays: China
ID NLM: 101242872

Informations de publication

Date de publication:
02 2022
Historique:
received: 30 08 2021
accepted: 15 11 2021
pubmed: 6 1 2022
medline: 11 2 2022
entrez: 5 1 2022
Statut: ppublish

Résumé

Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, effective vaccines are essential to control the current coronavirus disease 2019 (COVID-19) pandemic. Plant-derived virus-like particle (VLP) vaccine candidates have previously demonstrated immunogenicity and efficacy against influenza. Here, we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a VLP bearing a SARS-CoV-2 spike protein (CoVLP) vaccine candidate formulated with or without Adjuvant System 03 (AS03) or cytidine-phospho-guanosine (CpG) 1018. Although a single dose of the unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses, booster immunization (at 28 days after priming) and adjuvant administration significantly improved both responses, with higher immunogenicity and protection provided by the AS03-adjuvanted CoVLP. Fifteen micrograms of CoVLP adjuvanted with AS03 induced a polyfunctional interleukin-2 (IL-2)-driven response and IL-4 expression in CD4 T cells. Animals were challenged by multiple routes (i.e., intratracheal, intranasal, and ocular) with a total viral dose of 10

Identifiants

pubmed: 34983950
doi: 10.1038/s41423-021-00809-2
pii: 10.1038/s41423-021-00809-2
pmc: PMC8727235
doi:

Substances chimiques

Adjuvants, Immunologic 0
Antibodies, Neutralizing 0
Antibodies, Viral 0
COVID-19 Vaccines 0
Drug Combinations 0
Polysorbates 0
Recombinant Proteins 0
Spike Glycoprotein, Coronavirus 0
Vaccines, Virus-Like Particle 0
spike protein, SARS-CoV-2 0
Squalene 7QWM220FJH
AS03 adjuvant A7YT618XBV
alpha-Tocopherol H4N855PNZ1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

222-233

Subventions

Organisme : NIH HHS
ID : P51 OD011104
Pays : United States

Informations de copyright

© 2021. The Author(s).

Références

Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020;11:1620.
pubmed: 32221306 pmcid: 7100515 doi: 10.1038/s41467-020-15562-9
Li F. Structure, function, and evolution of coronavirus spike proteins. Annu Rev Virol. 2016;3:237–61.
pubmed: 27578435 pmcid: 5457962 doi: 10.1146/annurev-virology-110615-042301
Grant OC, Montgomery D, Ito K, Woods RJ. Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition. Sci Rep. 2020;10:14991.
pubmed: 32929138 pmcid: 7490396 doi: 10.1038/s41598-020-71748-7
Hoffmann M, Kleine-Weber H, Pohlmann S. A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells. Mol Cell. 2020;78:779–84.e775.
pubmed: 32362314 pmcid: 7194065 doi: 10.1016/j.molcel.2020.04.022
D'aoust MA, Couture MM, Charland N, Trépanier S, Landry N, Ors F, et al. The production of hemagglutinin-based virus-like particles in plants: a rapid, efficient and safe response to pandemic influenza. Plant Biotechnol J. 2010;8:607–19.
pubmed: 20199612 doi: 10.1111/j.1467-7652.2009.00496.x
Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. The spike protein of SARS-CoV-a target for vaccine and therapeutic development. Nat Rev Microbiol. 2009;7:226–36.
pubmed: 19198616 pmcid: 2750777 doi: 10.1038/nrmicro2090
Pallesen J, Wang N, Corbett KS, Wrapp D, Kirchdoerfer RN, Turner HL, et al. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc Natl Acad Sci USA. 2017;114:E7348–57.
pubmed: 28807998 pmcid: 5584442 doi: 10.1073/pnas.1707304114
Del Giudice G, Rappuoli R, Didierlaurent AM. Correlates of adjuvanticity: a review on adjuvants in licensed vaccines. Semin Immunol. 2018;39:14–21.
pubmed: 29801750 doi: 10.1016/j.smim.2018.05.001
Shirota H, Klinman DM. Recent progress concerning CpG DNA and its use as a vaccine adjuvant. Expert Rev Vaccines. 2014;13:299–312.
pubmed: 24308579 doi: 10.1586/14760584.2014.863715
Campbell JD. Development of the CpG adjuvant 1018: a case study. Methods Mol Biol. 2017;1494:15–27.
pubmed: 27718183 doi: 10.1007/978-1-4939-6445-1_2
Morel S, Didierlaurent A, Bourguignon P, Delhaye S, Baras B, Jacob V, et al. Adjuvant System AS03 containing alpha-tocopherol modulates innate immune response and leads to improved adaptive immunity. Vaccine. 2011;29:2461–73.
pubmed: 21256188 doi: 10.1016/j.vaccine.2011.01.011
Burny W, Callegaro A, Bechtold V, Clement F, Delhaye S, Fissette L, et al. Different adjuvants induce common innate pathways that are associated with enhanced adaptive responses against a model antigen in humans. Front Immunol. 2017;8:943.
pubmed: 28855902 pmcid: 5557780 doi: 10.3389/fimmu.2017.00943
De Mot L, Bechtold V, Bol V, Callegaro A, Coccia M, Essaghir A, et al. Transcriptional profiles of adjuvanted hepatitis B vaccines display variable interindividual homogeneity but a shared core signature. Sci Transl Med. 2020;12:eaay8618.
pubmed: 33177181 doi: 10.1126/scitranslmed.aay8618
Howard LM, Goll JB, Jensen TL, Hoek KL, Prasad N, Gelber CE, et al. AS03-adjuvanted H5N1 avian influenza vaccine modulates early innate immune signatures in human peripheral blood mononuclear cells. J Infect Dis. 2019;219:1786–98.
pubmed: 30566602 doi: 10.1093/infdis/jiy721
Khurana S, Coyle EM, Manischewitz J, King LR, Gao J, Germain RN, et al. AS03-adjuvanted H5N1 vaccine promotes antibody diversity and affinity maturation, NAI titers, cross-clade H5N1 neutralization, but not H1N1 cross-subtype neutralization. NPJ Vaccines. 2018;3:40.
pubmed: 30302282 pmcid: 6167326 doi: 10.1038/s41541-018-0076-2
Leroux-Roels I, Borkowski A, Vanwolleghem T, Dramé M, Clement F, Hons E, et al. Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. Lancet. 2007;370:580–9.
pubmed: 17707753 doi: 10.1016/S0140-6736(07)61297-5
Moris P, van der Most R, Leroux-Roels I, Clement F, Dramé M, Hanon E, et al. H5N1 influenza vaccine formulated with AS03 A induces strong cross-reactive and polyfunctional CD4 T-cell responses. J Clin Immunol. 2011;31:443–54.
pubmed: 21174144 doi: 10.1007/s10875-010-9490-6
Cohet C, van der Most R, Bauchau V, Bekkat-Berkani R, Doherty TM, Schuind A, et al. Safety of AS03-adjuvanted influenza vaccines: a review of the evidence. Vaccine. 2019;37:3006–21.
pubmed: 31031030 doi: 10.1016/j.vaccine.2019.04.048
Ward BJ, Gobeil P, Séguin A, Atkins J, Boulay I, Charbonneau PY, et al. Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19. Nat Med. 2021;27:1071–8.
pubmed: 34007070 pmcid: 8205852 doi: 10.1038/s41591-021-01370-1
Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367:1260–3.
pubmed: 32075877 pmcid: 7164637 doi: 10.1126/science.abb2507
Röltgen K, Powell AE, Wirz OF, Stevens BA, Hogan CA, Najeeb J, et al. Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome. Sci Immunol. 2020;5:eabe0240.
pubmed: 33288645 pmcid: 7857392 doi: 10.1126/sciimmunol.abe0240
Fahlberg MD, Blair RV, Doyle-Meyers LA, Midkiff CC, Zenere G, Russell-Lodrigue KE, et al. Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates. Nat Commun. 2020;11:6078.
pubmed: 33247138 pmcid: 7695721 doi: 10.1038/s41467-020-19967-4
Blair RV, Vaccari M, Doyle-Meyers LA, Roy CJ, Russell-Lodrigue K, Fahlberg M, et al. Acute respiratory distress in aged, SARS-CoV-2-infected African Green monkeys but not Rhesus macaques. Am J Pathol. 2021;191:274–82.
pubmed: 33171111 pmcid: 7648506 doi: 10.1016/j.ajpath.2020.10.016
Munster VJ, Feldmann F, Williamson BN, van Doremalen N, Pérez-Pérez L, Schulz J, et al. Respiratory disease in rhesus macaques inoculated with SARS-CoV-2. Nature. 2020;585:268–72.
pubmed: 32396922 pmcid: 7486227 doi: 10.1038/s41586-020-2324-7
Kim D, Lee JY, Yang JS, Kim JW, Kim VN, Chang H. The architecture of SARS-CoV-2 transcriptome. Cell. 2020;181:914–21.e910.
pubmed: 32330414 pmcid: 7179501 doi: 10.1016/j.cell.2020.04.011
Halperin SA, McNeil S, Langley JM, Smith B, MacKinnon-Cameron D, McCall-Sani R, et al. Safety and immunogenicity of different two-dose regimens of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in healthy young adults. Vaccine. 2012;30:5445–8.
pubmed: 22704926 doi: 10.1016/j.vaccine.2012.05.074
Heyward WL, Kyle M, Blumenau J, Davis M, Reisinger K, Kabongo ML, et al. Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared to a licensed hepatitis B vaccine in healthy adults 40–70 years of age. Vaccine. 2013;31:5300–5.
pubmed: 23727002 doi: 10.1016/j.vaccine.2013.05.068
Leroux-Roels G, Marchant A, Levy J, Van Damme P, Schwarz TF, Horsmans Y, et al. Impact of adjuvants on CD4(+) T cell and B cell responses to a protein antigen vaccine: Results from a phase II, randomized, multicenter trial. Clin Immunol. 2016;169:16–27.
pubmed: 27236001 doi: 10.1016/j.clim.2016.05.007
Liang JG, Su D, Song TZ, Zeng Y, Huang W, Wu J, et al. S-Trimer, a COVID-19 subunit vaccine candidate, induces protective immunity in nonhuman primates. Nat Commun. 2021;12:1346.
pubmed: 33649323 pmcid: 7921634 doi: 10.1038/s41467-021-21634-1
Arunachalam PS, Walls AC, Golden N, Atyeo C, Fischinger S, Li C, et al. Adjuvanting a subunit COVID-19 vaccine to induce protective immunity. Nature. 2021;594:253–8.
pubmed: 33873199 doi: 10.1038/s41586-021-03530-2
Tauzin A, Nayrac M, Benlarbi M, Gong SY, Gasser R, Beaudoin-Bussières G, et al. A single dose of the SARS-CoV-2 vaccine BNT162b2 elicits Fc-mediated antibody effector functions and T cell responses. Cell Host Microbe. 2021;29:1137–150.e6.
pubmed: 34133950 pmcid: 8175625 doi: 10.1016/j.chom.2021.06.001
Yu J, Tostanoski LH, Peter L, Mercado NB, McMahan K, Mahrokhian SH, et al. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science. 2020;369:806–11.
pubmed: 32434945 pmcid: 7243363 doi: 10.1126/science.abc6284
Bartsch YC, Fischinger S, Siddiqui SM, Chen Z, Yu J, Gebre M, et al. Discrete SARS-CoV-2 antibody titers track with functional humoral stability. Nat Commun. 2021;12:1018.
pubmed: 33589636 pmcid: 7884400 doi: 10.1038/s41467-021-21336-8
McMahan K, Yu J, Mercado NB, Loos C, Tostanoski LH, Chandrashekar A, et al. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature. 2021;590:630–4.
pubmed: 33276369 doi: 10.1038/s41586-020-03041-6
Dan JM, Mateus J, Kato Y, Hastie KM, Yu ED, Faliti CE, et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021;371:eabf4063.
pubmed: 33408181 doi: 10.1126/science.abf4063
Nelde A, Bilich T, Heitmann JS, Maringer Y, Salih HR, Roerden M, et al. SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition. Nat Immunol. 2021;22:74–85.
pubmed: 32999467 doi: 10.1038/s41590-020-00808-x
Rydyznski Moderbacher C, Ramirez SI, Dan JM, Grifoni A, Hastie KM, Weiskopf D, et al. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell. 2020;183:996–1012.e1019.
pubmed: 33010815 pmcid: 7494270 doi: 10.1016/j.cell.2020.09.038
Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021;184:861–80.
pubmed: 33497610 pmcid: 7803150 doi: 10.1016/j.cell.2021.01.007
Chen J, Lau YF, Lamirande EW, Paddock CD, Bartlett JH, Zaki SR, et al. Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection. J Virol. 2010;84:1289–301.
pubmed: 19906920 doi: 10.1128/JVI.01281-09
Zhao J, Zhao J, Perlman S. T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice. J Virol. 2010;84:9318–25.
pubmed: 20610717 pmcid: 2937604 doi: 10.1128/JVI.01049-10
Zhao J, Zhao J, Mangalam AK, Channappanavar R, Fett C, Meyerholz DK, et al. Airway memory CD4(+) T cells mediate protective immunity against emerging respiratory coronaviruses. Immunity. 2016;44:1379–91.
pubmed: 27287409 pmcid: 4917442 doi: 10.1016/j.immuni.2016.05.006
Appay V, van Lier RA, Sallusto F, Roederer M. Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytom Part A. 2008;73:975–83.
doi: 10.1002/cyto.a.20643
Sant AJ, McMichael A. Revealing the role of CD4(+) T cells in viral immunity. J Exp Med. 2012;209:1391–5.
pubmed: 22851641 pmcid: 3420330 doi: 10.1084/jem.20121517
Seder RA, Darrah PA, Roederer M. T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol. 2008;8:247–58.
pubmed: 18323851 doi: 10.1038/nri2274
Tarke A, Sidney J, Methot N, Yu ED, Zhang Y, Dan JM, Goodwin B, et al. Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals. Cell Rep Med. 2021;20:e100355.
Deng N, Weaver JM, Mosmann TR. Cytokine diversity in the Th1-dominated human anti-influenza response caused by variable cytokine expression by Th1 cells, and a minor population of uncommitted IL-2+IFNgamma- Thpp cells. PLoS ONE. 2014;9:e95986.
pubmed: 24788814 pmcid: 4006810 doi: 10.1371/journal.pone.0095986
Weaver JM, Yang H, Roumanes D, Lee FE, Wu H, Treanor JJ, et al. Increase in IFNgamma(-)IL-2(+) cells in recent human CD4 T cell responses to 2009 pandemic H1N1 influenza. PLoS ONE. 2013;8:e57275.
pubmed: 23526940 pmcid: 3603952 doi: 10.1371/journal.pone.0057275
Crotty S. Follicular helper CD4 T cells (TFH). Annu Rev Immunol. 2011;29:621–63.
pubmed: 21314428 doi: 10.1146/annurev-immunol-031210-101400
Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production. Cytokine. 2015;75:14–24.
pubmed: 26044597 pmcid: 4532589 doi: 10.1016/j.cyto.2015.05.010
Mercado NB, Zahn R, Wegmann F, Loos C, Chandrashekar A, Yu J, et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature. 2020;586:583–8.
pubmed: 32731257 pmcid: 7581548 doi: 10.1038/s41586-020-2607-z
McGonagle D, Sharif K, O’Regan A, Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020;19:102537.
pubmed: 32251717 pmcid: 7195002 doi: 10.1016/j.autrev.2020.102537
Pandolfi L, Fossali T, Frangipane V, Bozzini S, Morosini M, D'Amato M, et al. Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome. BMC Pulm Med. 2020;20:301.
pubmed: 33198751 pmcid: 7668012 doi: 10.1186/s12890-020-01343-z
Ye J, Zhang B, Xu J, Chang Q, McNutt MA, Korteweg C, et al. Molecular pathology in the lungs of severe acute respiratory syndrome patients. Am J Pathol. 2007;170:538–45.
pubmed: 17255322 pmcid: 1851867 doi: 10.2353/ajpath.2007.060469
Carsana L, Sonzogni A, Nasr A, Rossi RS, Pellegrinelli A, Zerbi P, et al. Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. Lancet Infect Dis. 2020;20:1135–40.
pubmed: 32526193 pmcid: 7279758 doi: 10.1016/S1473-3099(20)30434-5
Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med. 2020;8:681–6.
pubmed: 32473124 pmcid: 7255143 doi: 10.1016/S2213-2600(20)30243-5
Schurink B, Roos E, Radonic T, Barbe E, Bouman C, de Boer HH, et al. Viral presence and immunopathology in patients with lethal COVID-19: a prospective autopsy cohort study. Lancet Microbe. 2020;1:e290–99.
pubmed: 33015653 pmcid: 7518879 doi: 10.1016/S2666-5247(20)30144-0
Richmond P, Hatchuel L, Dong M, Ma B, Hu B, Smolenov I, et al. Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomised, double-blind, placebo-controlled trial. Lancet. 2021;397:682–94.
pubmed: 33524311 pmcid: 7906655 doi: 10.1016/S0140-6736(21)00241-5

Auteurs

Stéphane Pillet (S)

Medicago Inc., Québec, QC, Canada.

Prabhu S Arunachalam (PS)

Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.

Guadalupe Andreani (G)

Medicago Inc., Québec, QC, Canada.

Nadia Golden (N)

Tulane National Primate Research Center, Covington, LA, USA.

Jane Fontenot (J)

New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.

Pyone Pyone Aye (PP)

Tulane National Primate Research Center, Covington, LA, USA.

Katharina Röltgen (K)

Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.

Gabrielle Lehmicke (G)

Tulane National Primate Research Center, Covington, LA, USA.

Philipe Gobeil (P)

Medicago Inc., Québec, QC, Canada.

Charlotte Dubé (C)

Medicago Inc., Québec, QC, Canada.

Sonia Trépanier (S)

Medicago Inc., Québec, QC, Canada.

Nathalie Charland (N)

Medicago Inc., Québec, QC, Canada.

Marc-André D'Aoust (MA)

Medicago Inc., Québec, QC, Canada.

Kasi Russell-Lodrigue (K)

Tulane National Primate Research Center, Covington, LA, USA.

Christopher Monjure (C)

Tulane National Primate Research Center, Covington, LA, USA.

Robert V Blair (RV)

Tulane National Primate Research Center, Covington, LA, USA.

Scott D Boyd (SD)

Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.

Rudolf P Bohm (RP)

Tulane National Primate Research Center, Covington, LA, USA.

Jay Rappaport (J)

Tulane National Primate Research Center, Covington, LA, USA.
Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA, USA.

François Villinger (F)

New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA.

Nathalie Landry (N)

Medicago Inc., Québec, QC, Canada.

Bali Pulendran (B)

Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Institute for Immunity, Transplantation & Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.

Brian J Ward (BJ)

Medicago Inc., Québec, QC, Canada. Wardb@medicago.com.
Research Institute of the McGill University Health Centre, Montreal, QC, Canada. Wardb@medicago.com.

Articles similaires

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male
Humans Meals Time Factors Female Adult

Classifications MeSH