An efficient approach for SARS-CoV-2 monoclonal antibody production via modified mRNA-LNP immunization.
Int J Pharm
; 627: 122256, 2022 Nov 05.
Article
en En
| MEDLINE
| ID: mdl-36198358
ABSTRACT
Throughout the COVID-19 pandemic, many prophylactic and therapeutic drugs have been evaluated and introduced. Among these treatments, monoclonal antibodies (mAbs) that bind to and neutralize SARS-CoV-2 virus have been applied as complementary and alternative treatments to vaccines. Although different methodologies have been utilized to produce mAbs, traditional hybridoma fusion technology is still commonly used for this purpose due to its unmatched performance record. In this study, we coupled the hybridoma fusion strategy with mRNA-lipid nanoparticle (LNP) immunization. This time-saving approach can circumvent biological and technical hurdles, such as difficult-to-express membrane proteins, antigen instability, and the lack of posttranslational modifications on recombinant antigens. We used mRNA-LNP immunization and hybridoma fusion technology to generate mAbs against the receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein. Compared with traditional protein-based immunization approaches, inoculation of mice with RBD mRNA-LNP induced higher titers of serum antibodies and markedly increased serum neutralizing activity. The mAbs we obtained can bind to SARS-CoV-2 RBDs from several variants. Notably, RBD-mAb-3 displayed particularly high binding affinities and neutralizing potencies against both Alpha and Delta variants. In addition to introducing specific mAbs against SARS-CoV-2, our data generally demonstrate that mRNA-LNP immunization may be useful to quickly generate highly functional mAbs against emerging infectious diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
/
2_ODS3
/
4_TD
Problema de salud:
1_doencas_nao_transmissiveis
/
2_enfermedades_transmissibles
/
4_pneumonia
Asunto principal:
SARS-CoV-2
/
COVID-19
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Pharm
Año:
2022
Tipo del documento:
Article
País de afiliación:
Taiwán