Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B.
Jun LiuPatrick BudylowskiReuben SamsonBryan D GriffinGiorgi BabuadzeBhavisha RathodKaren ColwillJumai A AbioyeJordan Ari SchwartzRyan LawLily YipSang Kyun AhnSerena ChauMaedeh NaghibosadatYuko AritaQueenie HuFeng Yun YueArinjay BanerjeeW Rod HardyKaren Louise MossmanSamira MubarekaRobert A KozakMichael S PollanenNatalia Martin OrozcoAnne-Claude GingrasEric G MarcussonMario A OstrowskiPublished in: Science advances (2022)
Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report the preclinical development of a lipid nanoparticle–formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern, including the Alpha, Beta, Gamma, and Delta lineages. No adverse effects were induced by PTX-COVID19-B in either mice or hamsters. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 2 clinical trial ongoing.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- coronavirus disease
- clinical trial
- immune response
- healthcare
- public health
- randomized controlled trial
- copy number
- type diabetes
- stem cells
- gene expression
- bone marrow
- dna methylation
- dendritic cells
- cell therapy
- skeletal muscle
- fatty acid
- metabolic syndrome
- climate change
- genome wide
- binding protein