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Details

Autor(en) / Beteiligte
Titel
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
Ist Teil von
  • Cellular & molecular immunology, 2022-02, Vol.19 (2), p.222-233
Ort / Verlag
China: Nature Publishing Group
Erscheinungsjahr
2022
Quelle
MEDLINE
Beschreibungen/Notizen
  • 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 plaque-forming units of SARS-CoV-2. Lower viral replication in nasal swabs and bronchoalveolar lavage fluid (BALF) as well as fewer SARS-CoV-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CoVLP adjuvanted with AS03. No clinical, pathologic, or virologic evidence of vaccine-associated enhanced disease was observed in vaccinated animals. The CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.
Sprache
Englisch
Identifikatoren
ISSN: 1672-7681
eISSN: 2042-0226
DOI: 10.1038/s41423-021-00809-2
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8727235
Format
Schlagworte
Adjuvants, Immunologic - administration & dosage, Adjuvants, Immunologic - adverse effects, alpha-Tocopherol - administration & dosage, alpha-Tocopherol - adverse effects, Animals, Antibodies, Neutralizing - blood, Antibodies, Neutralizing - immunology, Antibodies, Viral - blood, Antibodies, Viral - immunology, Antiviral agents, Bronchus, CD4 antigen, Chemotactic factors, Clinical trials, Coronaviruses, COVID-19, COVID-19 - epidemiology, COVID-19 - immunology, COVID-19 - prevention & control, COVID-19 - virology, COVID-19 vaccines, COVID-19 Vaccines - administration & dosage, COVID-19 Vaccines - adverse effects, CpG islands, Disease Models, Animal, Drug Combinations, Drug Compounding - methods, Immune response (cell-mediated), Immune response (humoral), Immunity, Humoral, Immunization, Immunogenicity, Immunogenicity, Vaccine - immunology, Inflammation, Influenza, Interleukin 2, Interleukin 4, Lymphocytes T, Macaca mulatta, Male, Nicotiana - metabolism, Pandemics, Pandemics - prevention & control, Plants, Polysorbates - administration & dosage, Polysorbates - adverse effects, Recombinant Proteins - immunology, Recombinant Proteins - metabolism, Respiration, SARS-CoV-2 - immunology, Severe acute respiratory syndrome coronavirus 2, Spike Glycoprotein, Coronavirus - immunology, Spike Glycoprotein, Coronavirus - metabolism, Spike protein, Squalene - administration & dosage, Squalene - adverse effects, Trachea, Treatment Outcome, Vaccination - methods, Vaccine development, Vaccines, Vaccines, Virus-Like Particle - administration & dosage, Vaccines, Virus-Like Particle - adverse effects, Virus-like particles

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