In a recent study published in the journal iScience, researchers evaluated the effectiveness of immunization with a bacterial peptide conjugated to the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) against infection for SARS-CoV-2.
Study: Vaccination with a bacterial peptide conjugated to SARS-CoV-2 RBD accelerates immunity and protects against COVID-19. Image credit: BaLL LunLa / Shutterstock
The constant emergence of new variants of SARS-CoV-2 has negatively affected the efficacy and impact of coronavirus 2019 (COVID-19) vaccines against infections and the severity of the disease. Therefore, new vaccine platforms are needed to develop effective and safe vaccination regimens against SARS-CoV-2 infections and related hospitalization.
About the study
In the present study, the researchers used Boost immune technology (iBoost) to enhance the immune system’s response to the SARS-CoV-2 (S) RBD spike.
The team achieved immune recognition of SARS-CoV-2 RBD by conjugating the sequence to a chimeric design peptide (CDP) designed by the researchers. CDP consists of groups of amino acids that have charged side chains or bulky hydrophilic groups, derived from three different bacterial proteins, namely ZapB, which is the cell-splitting protein, IbpA, which is a small shock protein. thermal, and TFP (fimbrial protein type I). . The developed conjugated protein called CPD-RBD was expressed and purified.
The immunogenicity of conjugated CPD-RBD in vivo was assessed and compared with the corresponding unconjugated RBD by immunizing BALB / c mice with each protein purified on day 0 by primary vaccination and on day 14 by booster vaccination. The team selected Montanide ISA 720 together with a pool-type receptor agonist 9 called the CpG 1826 oligonucleotide as the vaccine adjuvant. Serological samples were collected from mice prior to immunization on day 0 and days 13, 21, 28, and 35. Samples were further analyzed for the presence of anti-RBD antibodies by an enzyme-linked immunosorbent assay (ELISA). ).
In addition, the team evaluated the production of IgG1 and IgG2b, which accounted for skewed T-helper (Th) -2 immune responses, and IgG2a and IgG3, which correlated with the stimulation of a Th1 response. The researchers also immunized the mice with CPD-RBD or RBD alone along with Sepivac (Sep), which was a vaccine adjuvant used instead of Montanide.
Results
The results of the study showed that adding the DCP component to the SARS-CoV-2 RBD increased the solubility and protein yield of the resulting CPD-RBD conjugate protein. In silico analysis of the conjugated protein sequence showed the alpha or beta chain helix domains. In addition, B and T cell epitopes observed on silico analysis indicated potent immune recognition.
The team did not find antibodies against SARS-CoV-2 RBD in the preimmune serum samples collected on day 0. However, on day 13, seroconversion was observed in a few mice belonging to the two groups that were vaccinated by the conjugate. and the unconjugated. purified proteins. In addition, on day 21, all mice that received the CPD-RBD vaccine showed robust levels of immunoglobulin (Ig) against viral RBD. In addition, on day 21, only 50% of RBD-immunized mice revealed a strong RBD-specific humoral response while no anti-RBD antibodies were found in two of the 10 mice vaccinated with unconjugated RBD protein. This suggested that RBD had moderate immunogenicity.
In addition, the difference in total anti-RBD Ig levels between the two vaccinated cohorts decreased at later time points. However, antibody titers corresponding to RBD-immunized mice were lower than those vaccinated with CPD-RBD three weeks after mice were vaccinated with the booster dose. This indicated that the iBoost platform obtained faster and more robust anti-RBD antibody responses compared to RBD alone.
Analysis of IgG subclasses showed that on day 21, mice immunized with CDP-RBD had substantially higher concentrations of anti-RBD IgG3 and IgG1 compared to RBD-vaccinated mice. In addition, the team observed an increasingly robust and consistent IgG2 response trend among mice immunized with CDP-RBD. In addition, vaccination with CDP-RBD, and not without conjugation with RBD, resulted in a greater ability to mount complete IgG1, IgG2a, IgG2b, and IgG3 responses. Thus, the CPD-RBD vaccine showed a more complete response against SARS-CoV-2 RBD, even seven days after booster vaccination.
Analysis with Sep as a vaccine adjuvant revealed that CDP-RBD / Sep induced higher levels of total anti-RBD IgG compared to the RBD / Sep vaccine, which was also observed for CDP-RBD with Montanide. This indicated that CDP was the key component that increased the humoral immune response. In addition, a substitute neutralization assay showed that serum obtained from the vaccine immunized with CPD-RBD resulted in higher levels of inhibition of the binding of the angiotensin-2-converting enzyme (ACE- 2) of RBD from day 21 compared to the serum obtained from mice. who were immunized only with RBD.
Conclusion
Overall, the study’s findings showed that CPD-RBD vaccination elicited a potent immune response and also protected against the severe symptoms associated with COVID-19.
Magazine reference:
- Blanas, A., Karsjens, H., de Ligt, A., Huijbers, EJM, van Loon, K., Denisov, S., Durukan, C., Engbersen, D., Groen, J., Hennig, S. , Hackeng, T., van Beijnum, JR, Griffioen, AW (2022). Vaccination with a bacterial peptide conjugated to SARS-CoV-2 RBD accelerates immunity and protects against COVID-19. SCIENCE. two: