COVID-19 vaccination with bacterial peptides bound to the receptor binding domain elicits a strong immune response

In a recent study published in iScience Journals and researchers evaluated the efficiency of immunization by bacterial peptides bound to the SARS-CoV-2 receptor-binding domain for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection against SARS-CoV-2 infection.

The constant emergence of new SARS-CoV-2 mutants Effectiveness Effect of Coronavirus Disease 2019 (COVID-19) vaccine on infection and disease severity. Therefore, a new vaccine platform is needed to develop effective and safe vaccination regimens for SARS-CoV-2 infections and associated hospitalizations.

About research

In this study, researchers adopted immune boost (iBoost) technology to improve the immune system’s response to SARS-CoV-2 spike (S) RBD.

The team achieved immune recognition of SARS-CoV-2RBD by binding a sequence to a chimeric designer peptide (CDP) designed by researchers. CDP has either a charged side chain or a bulky hydrophilic group derived from three different bacterial proteins: the cell division protein ZapB, the small heat shock protein IbpA, and the TFP (type I fimbria protein). It is composed of clusters of amino acids. .. A developed complex protein named CPD-RBD was expressed and purified.

Immunogenicity of conjugated CPD-RBD In vivo BALB / c mice were evaluated and compared to the corresponding unbound RBD by immunizing BALB / c mice with each purified protein on day 0 by primary vaccination and by booster vaccination on day 14. The team selected Montanede ISA720 as a vaccine adjuvant with a Toll-like receptor 9 agonist called the CpG1826 oligonucleotide. Serological samples were collected from mice on days 0 and 13, 21, 28, and 35 prior to immunization. Samples were further analyzed for the presence of anti-RBD antibody using enzyme-linked immunosorbent assay (ELISA).

In addition, the team evaluated IgG1 and IgG2b, which represent a T-helper (Th) -2 skew immune response, and IgG2a and IgG3, which correlate with stimulation of the Th1 response. Researchers also immunized mice with CPD-RBD or RBD alone, along with Sepivac (Sep), a vaccine adjuvant used in place of Montanide.

result

Research results have shown that the addition of the DCP component to SARS-CoV-2 RBD increases solubility and protein yield of the resulting complex protein CPD-RBD. The In silico Analysis of the complex protein sequence showed an alpha helix or beta strand domain.In addition, with B cells T cells Epitope observed in In silico Analysis showed strong immune recognition.

The team did not find antibodies to SARS-CoV-2 RBD in pre-immune serum samples collected on day 0. However, seroconversion was observed by day 13 in several mice belonging to both the conjugated and non-conjugated groups. Purified protein. In addition, by day 21, all mice receiving the CPD-RBD vaccine showed potent immunoglobulin (Ig) levels against the viral RBD. Also, by day 21, only 50% of RBD-immunized mice showed a strong RBD-specific humoral response, whereas in 2 of 10 mice vaccinated with the unbound RBD protein. No anti-RBD antibody was found. This suggested that RBD has moderate immunogenicity.

In addition, the difference in total anti-RBD Ig levels between the two vaccinated cohorts was reduced at subsequent time points. However, antibody titers corresponding to RBD-immunized mice were lower than those in CPD-RBD vaccinated 3 weeks after the mice were vaccinated at the booster dose. This indicates that the iBoost platform elicited a faster and more robust anti-RBD antibody response compared to RBD alone.

Analysis of the IgG subclass showed that by day 21, CDP-RBD immunized mice had substantially higher concentrations of both anti-RBD IgG3 and IgG1 compared to RBD-vaccinated mice. Indicated. In addition, the team noted a trend toward increasingly robust and consistent IgG2 responses among mice immunized with CDP-RBD. In addition, vaccination with CDP-RBD was not without binding to RBD and increased the ability to initiate a complete IgG1, IgG2a, IgG2b, and IgG3 responses. Therefore, the CPD-RBD vaccine showed a more comprehensive response to SARS-CoV-2RBD even 7 days after booster vaccination.

Analysis using Sep as a vaccine adjuvant reveals that CDP-RBD / Sep induces higher levels of anti-RBD total IgG compared to the RBD / Sep vaccine also observed with CDP-RBD containing montanide. became. This indicates that CDP is an important factor in enhancing the humoral immune response. In addition, in the surrogate neutralization assay, sera obtained from the CPD-RBD immunized vaccine bind to RBD-angiotensin converting enzyme-2 (ACE-2) after day 21 compared to sera obtained from mice. It has been shown to result in higher levels of inhibition. Immune only with RBD.

Conclusion

Overall, research results have shown that CPD-RBD vaccination elicits a strong immune response and protects against the severe symptoms associated with COVID-19.