BNT162b2 (Pfizer- BioNTech) and mRNA 1273 (Moderna) vaccines were the first messenger RNA (mRNA)-based vaccines ever approved. In both vaccines, an mRNA sequence determines the structure and assembly of the immunogen, the SARS-CoV-2 spike (S) glycoprotein. In this study, the authors from Italy and the United Kingdom used mass spectrometry analysis to investigate the presence of recombinant S protein, encoded by the mRNA vaccine, in blood samples of participants vaccinated with mRNA COVID-19 vaccines.
The S protein appears to be a major pathogenic factor that contributes to the unique pathogenesis of SARS-CoV-2. The S protein plays three critical roles in facilitating host cell entry: it must bind to the host cell angiotensin-converting enzyme 2 receptor (ACE2), be proteolytically processed, and promote membrane fusion. Because of these reasons, it is one of the most important targets for vaccine development and therapeutic approaches against COVID-19.
The researchers noted that it is possible to distinguish synthetic and natural S proteins because they produce different tryptic digestion products. When digested by an enzyme, trypsin, the wild-type SAR-CoV-2 protein produces two smaller fragments, namely LDK + VEAEVQIDR. The recombinant S protein encoded by the mRNA vaccine produces an LDPPEAEVQIDR fragment (PP-spike marker).
Of note, numerous studies have shown that the S protein by itself, without the rest of the viral components, was sufficient to promote different pathological effects and cause damage to various cells and organs.
About the study
The study included 60 individuals, 20 vaccinated with the full cycle of mRNA vaccine, 20 unvaccinated controls who tested negative for COVID-19, and 20 unvaccinated controls who tested positive for COVID-19. The presence of specific fragments of recombinant S protein encoded by the mRNA vaccine (in this study called PP-spike) in biological samples was detected by mass spectrometry.
Approximately 50% of subjects who received mRNA-based vaccines had specific fragments of recombinant S protein in their blood samples. The minimum time when the PP-spike fragment was detected was 69 days after vaccination, whereas the maximum was 187 days.
The presence of circulating recombinant S protein was independent of the anti-SARS-CoV-2 IgG antibody titer.
All samples from 40 unvaccinated individuals (tested negative or positive for COVID-19) were negative for recombinant S protein.
Based on these results, the authors proposed several possible molecular mechanisms responsible for the persistence of the “PP spike fragment”- Figure 1.
Figure 1 from the article by Brogna C et al. Proteomics Clin. Appl. 2023
Conclusion
This study that used mass spectrometry analysis of blood samples showed that approximately 50% of subjects who received mRNA-based vaccines had specific fragments of recombinant S protein in their blood samples 2-6 months after vaccination. All blood samples from individuals who were not vaccinated were negative for recombinant S protein.
The authors emphasized that this study is the first proteomic detection of recombinant S protein in subjects who had been vaccinated. These results confirmed that this method allows the detection of circulating S protein encoded by an mRNA vaccine, and the evaluation of its half-life.
This article was published in Proteomics Clinical Application.
