Broad-spectrum coronavirus neutralization induced by hetero RBD-Fc protein vaccine.
J Med Virol
; 96(9): e29917, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39279390
ABSTRACT
In the landscape of infectious diseases, human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2 pose significant threats, characterized by severe respiratory illnesses and notable resistance to conventional treatments due to their rapid evolution and the emergence of diverse variants, particularly within SARS-CoV-2. This study investigated the development of broad-spectrum coronavirus vaccines using heterodimeric RBD-Fc proteins engineered through the "Knob-into-Hole" technique. We constructed various recombinant proteins incorporating the receptor-binding domains (RBDs) of different coronaviruses. Heterodimers combining RBDs from SARS-CoV-2 with those of SARS-CoV or MERS-CoV elicited superior neutralizing responses compared to homodimeric proteins in murine models. Additionally, heterotetrameric proteins, specifically D614G_Delta/BA.1_XBB.1.5-RBD and MERS_D614G/BA.1_XBB.1.5-RBD, elicited remarkable breadth and potency in neutralizing all known SARS-CoV-2 variants, SARS-CoV, related sarbecoviruses like GD-Pangolin and WIV1, and even MERS-CoV pseudoviruses. Furthermore, these heterotetrameric proteins also demonstrated enhanced cellular immune responses. These findings underscore the potential of recombinant hetero proteins as a universal vaccine strategy against current and future coronavirus threats.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antibodies, Neutralizing
/
Spike Glycoprotein, Coronavirus
/
Middle East Respiratory Syndrome Coronavirus
/
COVID-19 Vaccines
/
SARS-CoV-2
/
Antibodies, Viral
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
J Med Virol
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Estados Unidos