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.
Adjuvants, Immunologic
/ administration & dosage
Animals
Antibodies, Neutralizing
/ blood
Antibodies, Viral
/ blood
COVID-19
/ epidemiology
COVID-19 Vaccines
/ administration & dosage
Disease Models, Animal
Drug Combinations
Drug Compounding
/ methods
Immunity, Humoral
Immunogenicity, Vaccine
/ immunology
Macaca mulatta
Male
Pandemics
/ prevention & control
Polysorbates
/ administration & dosage
Recombinant Proteins
/ immunology
SARS-CoV-2
/ immunology
Spike Glycoprotein, Coronavirus
/ immunology
Squalene
/ administration & dosage
Nicotiana
/ metabolism
Treatment Outcome
Vaccination
/ methods
Vaccines, Virus-Like Particle
/ administration & dosage
alpha-Tocopherol
/ administration & dosage
AS03
CpG1018
Non-humane primates
SARS-CoV-2
Virus-like particles
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
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
222-233Subventions
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