Broad-spectrum Delta-BA.2 tandem-fused heterodimer mRNA vaccine delivered by lipopolyplex.
PLoS Pathog
; 20(4): e1012116, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38557908
ABSTRACT
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to mutate and generates new variants with increasingly severe immune escape, urging the upgrade of COVID-19 vaccines. Here, based on a similar dimeric RBD design as our previous ZF2001 vaccine, we developed a novel broad-spectrum COVID-19 mRNA vaccine, SWIM516, with chimeric Delta-BA.2 RBD dimer delivered by lipopolyplex (LPP). Unlike the popular lipid nanoparticle (LNP), this LPP-delivered mRNA expresses only in the injection site, which avoids potential toxicity to the liver. We demonstrated the broad-spectrum humoral and cellular immunogenicity of this vaccine to Delta and Omicron sub-variants in naïve mice and as booster shots. When challenged with Delta or Omicron live virus, vaccinated human angiotensin-converting enzyme (hACE2) transgenic mice and rhesus macaques were both protected, displaying significantly reduced viral loads and markedly relieved pathological damages. We believe the SWIM516 vaccine qualifies as a candidate for the next-generation broad-spectrum COVID-19 vaccine.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
COVID-19
/
Vacinas de mRNA
Limite:
Animals
/
Humans
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China