Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add filters

Database
Language
Document Type
Year range
1.
Sci Rep ; 10(1): 20085, 2020 11 18.
Article in English | MEDLINE | ID: covidwho-933722

ABSTRACT

The COVID-19 pandemic is a worldwide health emergency which calls for an unprecedented race for vaccines and treatment. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein, S-2P. To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of neutralizing antibodies in sera of immunized mice against pseudotyped lentivirus reporter or live wild-type SARS-CoV-2. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018 and alum as a candidate vaccine to prevent COVID-19 disease.


Subject(s)
COVID-19 Vaccines/immunology , Immunogenicity, Vaccine , Spike Glycoprotein, Coronavirus/immunology , Adjuvants, Immunologic/therapeutic use , Aluminum Hydroxide/therapeutic use , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , CHO Cells , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/therapeutic use , Cricetinae , Cricetulus , Cytokines/blood , Cytokines/metabolism , Female , HEK293 Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Oligodeoxyribonucleotides/therapeutic use , Rats , Rats, Sprague-Dawley , Spleen/immunology , Th1 Cells/immunology
SELECTION OF CITATIONS
SEARCH DETAIL