A Phase1 Results of a Non-Stabilized Spike-Encoding mRNA Vaccine in Adults

Background

Effective COVID-19 mRNA vaccines are mainly available in high-income countries. ChulaCov19, a prefusion non-stabilized Spike protein-encoding, nucleoside-modified mRNA, lipid nanoparticle encapsulated vaccine development, aims to enhance accessibility of mRNA vaccine and future pandemic preparedness for low- to middle-income countries.

Methods

Seventy-two eligible volunteers, 36 aged 18-55 (adults) followed by 36 aged 56-75 (elderly) enrolled in a dose escalation study of ChulaCov19 mRNA vaccine. Two doses of vaccine were given 21 days apart at 10, 25, or 50 µg/dose (12/group). Safety was the primary and immunogenicity the secondary outcome. Human convalescents’ (HCS) and Pfizer/BioNTech vaccinees’ sera provided comparison panels.

Results

All three doses of ChulaCov19 were well tolerated and elicited robust dose-dependent and age- dependent B- and T-cell responses. Transient mild/moderate injection site pain, fever, chills, fatigue, and headache were more common after the second dose. Four weeks after the second ChulaCov19: dose at 10, 25, and 50 µg dose, MicroVNT-50 Geometric mean titer (GMT) against wild-type was 848, 736 and 1,140 IU/mL, respectively, versus 267 IU/mL for HCS. All dose levels elicited 100% seroconversion, with GMT ratio 4-8-fold higher than for HCS (p<0.01), and high IFNγ spot-forming cells/million peripheral blood mononuclear cells. The 50 µg dose induced better cross-neutralization against Alpha, Beta, Gamma, and Delta variants than lower doses.

Conclusions

ChulaCov19 at 50 µg/dose is well tolerated and elicited higher neutralizing antibodies than HCS with strong T-cell responses. These antibodies cross neutralized four variants of concern and ChulaCov19 has therefore proceeded to phase 2 and 3 clinical trials.

Trial registration number

<ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://ClinicalTrials.gov">ClinicalTrials.gov</ext-link> Identifier <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04566276">NCT04566276</ext-link>

Graphical Abstract