Studies have shown that low dose divalent unmodified mRNA vaccines against SARS-CoV-2 are highly effective.

In a recent study posted on bioRxiv* Preprint server, researchers compared the efficiency of monovalent and bivalent messenger ribonucleic acid (mRNA) vaccines with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The Coronavirus Disease 2019 (COVID-19) vaccine has contributed significantly to controlling the morbidity and mortality caused by pandemics. With the advent of new SARS-CoV-2 mutants, the development of newer and more effective vaccines and vaccine strategies is essential.

About research

In this study, the team developed an unmodified mRNA vaccine containing CV2CoV.351, CV2CoV.617, and CV2CoV encoding SARS-CoV-2. Spike protein Sequences from SARS-CoV-2 beta (B.1.351) and delta (B.1.617.2) variants, as well as wild-type strains. The monovalent vaccine consisted of CV2CoV.351, CV2CoV.617, and CV2CoV, and the bivalent vaccine consisted of CV2CoV.351 and CV2CoV.617.

The team injected K18-human angiotensin converting enzyme 2 (ACE2) transgenic mice with a low dose of 20 µL monovalent or bivalent vaccine or sodium chloride (NaCl) on days 0 and 28. These transgenic mice have human-like ACE2 receptors that serve as entry points for SARS-CoV-2.

Vaccinated mice were protected from SARS-CoV-2 exposure, and NaCl-injected mice were challenged with beta and delta variants on day 56. Cerebral samples were collected on day 10. In addition, the team investigated whether low concentrations of monovalent or bivalent vaccines could stimulate T cells present in lung parenchyma.

result

The results of the study showed that among mice injected with NaCl exposed to SARS-CoV-2, 67% of all beta-exposed and delta-exposed mice succumbed to the infection. rice field. The team found detectable amounts of SARS-CoV-2 genomic RNA or subgenomic RNA (sgRNA) in oral swabs or lung, cerebral, and cerebellum samples of all bivalent vaccinated beta-challenge mice except one. did not do it. This showed that productive infection was significantly prevented in infected mice.

However, the team noted that the prevention of SARS-CoV-2 replication by the monovalent vaccine in the upper respiratory tract (URT) depends on the virus exposed to mice.Reduced Viral load The turbinates of bivalent vaccinated mice were comparable to those of the corresponding monovalent vaccinated mice after exposure to beta. However, viral replication of the delta variant was completely prevented in all vaccination cohorts.

In addition, the team reported high levels of anti-receptor binding domain (RBD) total immunoglobulin levels in all vaccinated mice.Also, bivalent and monovalent vaccines are at equally high levels. Neutralizing antibody In mice exposed to beta and delta respectively. Overall, the levels of neutralizing antibodies induced by the bivalent vaccine were statistically higher than those of the monovalent vaccine, regardless of the mutant.

In addition, low concentrations of monovalent and bivalent vaccines induced potent SARS-CoV-2 pedplomer-specific CD4.⁺ And CD8⁺ Response compared to unvaccinated mice. Vaccination also caused enrichment of interferon gamma and granzyme B in the lung parenchyma.

Conclusion

The study results show that the effective viral clearance of the SARS-CoV-2 delta variant observed in the nasal turbinates of mice requires an assessment of the vaccine efficacy of divalent and higher valence vaccines. Shown. Researchers believe that further mRNA vaccines can be developed to adapt to the circulating and emerging SARS-CoV-2 mutants.

*Important Notices

bioRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.