RESUMO
The huge worldwide demand for vaccines targeting SARS-CoV-2 has necessitated the continued development of novel improved formulations capable of reducing the burden of the COVID-19 pandemic. Herein, we evaluated novel protein subunit vaccine formulations containing a resistin-trimerized spike antigen, SmT1. When combined with sulfated lactosyl archaeol (SLA) archaeosome adjuvant, formulations induced robust antigen-specific humoral and cellular immune responses in mice. Antibodies had strong neutralizing activity, preventing viral spike binding and viral infection. In addition, the formulations were highly efficacious in a hamster challenge model reducing viral load and body weight loss even after a single vaccination. The antigen-specific antibodies generated by our vaccine formulations had stronger neutralizing activity than human convalescent plasma, neutralizing the spike proteins of the B.1.1.7 and B.1.351 variants of concern. As such, our SmT1 antigen along with SLA archaeosome adjuvant comprise a promising platform for the development of efficacious protein subunit vaccine formulations for SARS-CoV-2.
Assuntos
Adjuvantes Imunológicos/química , Antígenos Arqueais/química , Vacinas contra COVID-19/uso terapêutico , Lipídeos/química , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Peso Corporal , COVID-19/terapia , Chlorocebus aethiops , Cricetinae , Citocinas/metabolismo , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunização Passiva , Mesocricetus , Camundongos , Camundongos Endogâmicos C57BL , Testes de Neutralização , Peptídeos/química , Domínios Proteicos , SARS-CoV-2 , Receptores Toll-Like/imunologia , Células Vero , Carga Viral , Soroterapia para COVID-19RESUMO
This minireview summarizes our current knowledge about archaeal genetic elements in the hyperthermophilic order Thermococcales in the phylum Euryarchaeota. This includes recent work on the first virus of Pyrococcus, PAV1, the discovery of novel unique virus morphotypes in hot deep-sea environments, and preliminary observations on novel cryptic plasmids. We also review the work accomplished over the last 5 years in the development of genetic tools for members of the Pyrococcus and Thermococcus genera, mainly in our laboratories.