The mRNA vaccine BNT162b2 demonstrates impaired TH1 immunogenicity in human elders in vitro and aged mice in vivo.
Res Sq
; 2022 Dec 21.
Article
en En
| MEDLINE
| ID: mdl-36597547
ABSTRACT
mRNA vaccines have been key to addressing the SARS-CoV-2 pandemic but have impaired immunogenicity and durability in vulnerable older populations. We evaluated the mRNA vaccine BNT162b2 in human in vitro whole blood assays with supernatants from adult (18-50 years) and elder (≥60 years) participants measured by mass spectrometry and proximity extension assay proteomics. BNT162b2 induced increased expression of soluble proteins in adult blood (e.g., C1S, PSMC6, CPN1), but demonstrated reduced proteins in elder blood (e.g., TPM4, APOF, APOC2, CPN1, and PI16), including 30-85% lower induction of TH1-polarizing cytokines and chemokines (e.g., IFNγ, and CXCL10). Elder TH1 impairment was validated in mice in vivo and associated with impaired humoral and cellular immunogenicity. Our study demonstrates the utility of a human in vitro platform to model age-specific mRNA vaccine activity, highlights impaired TH1 immunogenicity in older adults, and provides rationale for developing enhanced mRNA vaccines with greater immunogenicity in vulnerable populations.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Res Sq
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos