Strategic development of a self-adjuvanting SARS-CoV-2 RBD vaccine: From adjuvant screening to enhanced immunogenicity with a modified TLR7 agonist.
Int Immunopharmacol
; 132: 111909, 2024 May 10.
Article
em En
| MEDLINE
| ID: mdl-38554446
ABSTRACT
Adjuvants enhance the body's immune response to a vaccine, often leading to better protection against diseases. Monophosphoryl lipid A analogues (MPLA, TLR4 agonists), α-galactosylceramide analogues (NKT cell agonists), and imidazoquinoline compounds (TLR7/8 agonists) are emerging novel adjuvants on market or under clinical trials. Despite significant interest in these adjuvants, a direct comparison of their adjuvant activities remains unexplored. We initially assessed the activities of various adjuvants from three distinct categories using the SARS-CoV-2 RBD trimer antigen. TLR4 and TLR7/8 agonists are discovered to elicit robust IgG2a/2b antibodies, which is crucial for eliciting antibody dependent cytotoxicity. While α-galactosylceramide analogs induced mainly IgG1 antibody. Then, because of the flexibility of the TLR7/8 agonist, we designed and synthesized a tri-component self-adjuvanting SARS-CoV-2 RBD vaccine, featuring a covalent TLR7 agonist and targeting mannoside. Animal studies indicated that this vaccine generated antigen-specific humoral immunity. Yet, its immunogenicity seems compromised, indicating the complexity of the vaccine.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adjuvantes Imunológicos
/
Receptor 7 Toll-Like
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Vacinas contra COVID-19
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SARS-CoV-2
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COVID-19
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China