Doggybone DNA COVID-19 vaccine can effectively neutralize SARS-CoV-2 mutants

In a recent study published in vaccination Journal, researchers evaluated Effectiveness of New Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Novel Bone Deoxyribonucleic Acid (DNA) Vaccine.

So far, different types of vaccines have been developed to attack different targets against coronavirus disease 2019 (COVID-19) infection. Among these Nucleic acid Vaccines such as the Doggybone DNA Vaccine (dbDNA Vaccine) have the advantage of rapid production because they require only easily modifiable viral antigen sequences to induce detected viral mutations.

About research

In this study, researchers compared a dbDNA vaccine containing the SARS-CoV-2 spike protein sequence (dbDNAS) with a plasmid DNA vaccine (nCoV-S).

The team developed a dbDNA and plasmid DNA vaccine using a similar SARS-CoV-2S protein sequence. Vaccines nCoV-S (JET) and dbDNAS (JET) facilitate a direct comparison of DNA immunogenicity and plasmid vaccines. The team vaccinated hamsters with a 0.2 or 0.05 mg vaccine via jet injection. Immunogenicity was then determined by SARS-CoV-2 pseudovirion production and pseudovirion assay (PsVNA) performed after the first and second doses of the vaccine.

dbDNAS（JET）、nCoV-S（JET）、およびdbDNAS（ST-JET）ワクチンの防御効率は、免疫抑制されたSARS-CoV-2ハムスターモデルを介して分析されました。 Immunized hamsters became immunocompromised by administration of cyclophosphamide and exposure of animals to 1000 PFU SARS-CoV-2 via the intranasal route. The team took lung tissue samples 9 days after infection (dpi) and evaluated viral ribonucleic acid (RNA) via infectious virus by real-time reverse transcription-polymerase chain reaction (rtRT-PCR) and plaque assay.

The team also evaluated whether the polyclonal antibody response induced by DNA vaccination with one of the dbDNAS (JET), nCoV-S (JET), and dbDNAS (ST-JET) vaccines had a cross-neutralizing effect. did. The plaque reduction neutralization test (PRNT) was performed using serum samples collected at week 5 against the SARS-CoV-2D614G mutant. The team also used variants such as beta, epsilon, iota, delta, and delta + to test the ability to neutralize sera obtained from hamsters immunized with high doses of either vaccine.

result

The study results showed that all hamsters showed neutralizing titers after the second immunization, except for one hamster vaccinated with the 0.05 mg dbDNAS vaccine. The highest levels of neutralization were seen in the dbDNAS and nCoV-S groups, regardless of the number of vaccine doses administered. The team noted a significant increase in PsVNA titers after vaccination with the second nCoV-S dose compared to control participants who received simulated vaccination.

In the assessment of vaccinated immunosuppressive hamsters, all vaccinated with a dose of 0.2 mg dbDNAS (ST-JET) at 7-9 dpi, a dose of 0.2 mg dbDNAS (JET) at 8-9 dpi, or 0.2. There was a significant difference in hamster weight. MgnCoV-S (JET) dose at 9dpi. In addition, the geometric mean of viral RNA copies from infectious virus and lung samples was smaller than in negative DNA control samples. Overall, this indicates that a 0.2 mg dose of either the dbDNAS (ST-JET) or nCoV-S (JET) vaccine has a protective effect against hamsters exposed to SARS-CoV-2. Shown. This reduced body weight, viral RNA, and infectious virus found in lung samples. In addition, hamsters vaccinated with either 0.5 mg dbDNAS (ST-JET), nCoV-S (JET), or dbDNAS (JET) vaccines had a significantly reduced protective effect.

The team also noted that serological samples from nCoV-S (JET) vaccinated hamsters showed the highest neutralizing titers for the D614G mutant. Moreover, there was no significant difference in the efficacy of the vaccine against different mutants. In particular, all three vaccines tested in this study induced crossover.Neutralizing antibody For all SARS-CoV-2 variants evaluated. The response observed in hamsters vaccinated with the dbDNAS (JET) vaccine was significantly lower than in the other two vaccines, with one hamster having anti-Iota antibody and two having anti-beta antibody.

In addition, nCoV-S (JET) samples showed delta and delta + variant neutralization in a statistically different way compared to beta variants. The variation observed between the ability to neutralize the Iota and Delta mutants was also significant within the nCoV-S (JET) vaccinated cohort.

Conclusion

Overall, the study results showed that the puppy bone DNA COVID-19 vaccine can effectively neutralize the SARS-CoV-2 mutant of interest. In addition, serological samples of animals vaccinated with the novel DNA vaccine showed effective levels of antibody neutralization against various SARS-CoV-2 mutants.