Immunogenicity and Protective Efficacy of a SARS-CoV-2 mRNA Vaccine Encoding Secreted Non-Stabilized Spike Protein in Mice
Open accessAbstract
Establishment of an mRNA vaccine platform in low- and middle-income countries (LMICs) is important to enhance vaccine accessibility and ensure future pandemic preparedness. Here, we describe the preclinical studies of a SARS-CoV-2 mRNA encoding prefusion-unstabilized ectodomain spike protein encapsulated in lipid nanoparticles (LNP) “ChulaCov19”. In BALB/c mice, ChulaCov19 at 0.2, 1, 10, and 30 μg given 2 doses, 21 days apart, elicited robust neutralizing antibody (NAb) and T cells responses in a dose-dependent relationship. The geometric mean titer (GMT) of micro-virus neutralizing (micro-VNT) antibody against wild-type virus was 1,280, 11,762, 54,047, and 62,084, respectively. Higher doses induced better cross-neutralizing antibody against Delta and Omicron variants. This elicited specific immunogenicity was significantly higher than those induced by homologous prime-boost with inactivated (CoronaVac) or viral vector (AZD1222) vaccine. In heterologous prime-boost study, mice primed with either CoronaVac or AZD1222 vaccine and boosted with 5 μg ChulaCov19 generated NAb 7-fold higher against wild-type virus (WT) and was also significantly higher against Omicron (BA.1 and BA.4/5) than homologous CoronaVac or AZD1222 vaccination. AZD1222-prime/mRNA-boost had mean spike-specific IFNγ positive T cells of 3,725 SFC/10 6 splenocytes, which was significantly higher than all groups except homologous ChulaCov19. Challenge study in human-ACE-2-expressing transgenic mice showed that ChulaCov19 at 1 μg or 10 μg protected mice from COVID-19 symptoms, prevented SARS-CoV-2 viremia, significantly reduced tissue viral load in nasal turbinate, brain, and lung tissues 99.9-100%, and without anamnestic of Ab response which indicated its protective efficacy. ChulaCov19 is therefore a promising mRNA vaccine candidate either as a primary or a boost vaccination and has entered clinical development.
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In rodent and macaques, ChulaCov19 elicited strong B- and T-cell responses.
“In rodent and macaques, ChulaCov19 elicited strong B-and T-cell responses 3 .”
From Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial (2022) · cites this paper as [3]
The Abstract (page unavailable) reports robust neutralizing-antibody and T-cell responses to ChulaCov19 in BALB/c mice, supporting the rodent portion of the claim. The cited paper does not report ChulaCov19 B- or T-cell responses in macaques; a search for macaques returned only mouse experiments and unrelated references to monkey-derived cells. (LLM, conf=0.88)
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Gatechompol, S., Kittanamongkolchai, W., Ketloy, C., Prompetchara, E., Thitithanyanont, A., Jongkaewwattana, A., Buranapraditkun, S., Alameh, M.-G., Ubolyam, S., Sophonphan, J., et al. (2022) · Nature Microbiology · doi:10.1038/s41564-022-01271-0 · Cited by 15 · see citing works
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- Authors
- Prompetchara, E., Ketloy, C., Alameh, M.-G., Tarakhet, K., Kaewpang, P., Yostrerat, N., Pitakpolrat, P., Buranapraditkun, S., Manopwisedcharoen, S., Thitithanyanont, A., Jongkaewwattana, A., Hunsawong, T., Im-Erbsin, R., Reed, M., Wijagkanalan, W., Patarakul, K., Palaga, T., Lam, K., Heyes, J., Weissman, D., & Ruxrungtham, K.
- Affiliations
- Chulalongkorn University (TH)
- University of Pennsylvania (US)
- Mahidol University (TH)
- National Science and Technology Development Agency (TH)
- Armed Forces Research Institute of Medical Science (TH)
- Biotronik (Singapore) (SG)
- Corresponding author
- Ketloy, Chutitorn
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2022-09-07
- OpenAlex
- W4295012182
- Cited by
- 1
- References
- 41
- Citations by year
- 2022: 1
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Funders
- Chulalongkorn University (764002-HE04)
- National Research Council of Thailand
- Faculty of Medicine, Chulalongkorn University
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, mRNA vaccines, lipid nanoparticles, neutralizing antibodies, T cell response, Omicron variant, Delta variant, heterologous prime-boost, inactivated vaccine, AZD1222, vaccine access, low- and middle-income countries, challenge protection
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