Study Of SARS-CoV-2 Variant MRNA Vaccine

With the continued emergence of Severe Acute Respiratory Syndrome Coronavirus 2(SARS CoV-2)variants,all currently marketed vaccines have significantly reduced neutralizing protection against the latest variant of concern(VOC),Omicron.Therefore,there is an urgent need to develop a SARS-CoV-2 mRNA vaccine with cross-neutralizing effects.In this study,we designed a Delta receptor binding domain(RBD)-based mRNA molecule and used a lipid nanoparticle(LNPs)delivery platform to develop a SARS-CoV-2 mRNA vaccine candidate with efficient cross-neutralization,termed mRNA-D2-LNP.Two intramuscular immunizations with mRNA-D2-LNP elicited a robust humoral immune response and a durable T-cell immune response in mice.mRNA-D2-LNP showed significant crossneutralizing activity,inducing high titers of neutralizing antibodies against a variety of SARSCoV-2 variants,including wild-type(WT),Beta,BA.1,BA.2 and BA.4/5 variants.The neutralizing antibody titers(NT50)against WT,Beta,Delta,BA.1,BA.2 and BA.4/5 were 1/26,032,1/9,656,1/109,030,1/7,922,1/6,715 and 1/6,047 after booster immunization of mice with 10 μg of mRNA-D2-LNP,respectively.In addition to this,mice immunised twice intramuscularly with mRNA-D2-LNP achieved long-lasting neutralizing protection,with neutralizing antibody titers still as high as 1/7,348 after 8 months.Furthermore,the intranasal challenge of mice with BA.1(3.0 × 103 TCID50)showed that mRNA-D2-LNP immunization resulted in a 2 log per gram decrease in viral RNA copy number in the tissues of the upper and lower respiratory tracts of mice,which suggests that mRNA-D2-LNP protects mice from BA.1 virus infection.In conclusion,we have developed a broad-spectrum SARS-COV-2 variant mRNA vaccine candidate that maintains neutralizing activity against Omicron variants,shows long-term stability at conventional low temperatures,and has a good safety,which may be developed into a novel broad-spectrum SARS-COV-2 mRNA vaccine candidate.