A single dose of BNT162b2 mRNA induces humoral and T cell responses to mutants with a history of COVID-19

Some of the currently approved COVID-19 vaccines utilize messenger RNA (mRNA) technology to encode the production of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Spike protein..

Most reports show that these vaccines strongly induce the production of antibodies against peplomers, especially the receptor-binding domain (RBD), after two doses that are normally prescribed. However, the involvement of CD4 + and CD8 + memory T cells is essential for inducing long-term immunity and has not been well studied.

Papers recently uploaded to the preprint server bioRxiv* Tozan et al.. (March 18th^th, 2021) The ability of a single dose of mRNA vaccine to induce humoral and T cell responses to mutants has been demonstrated and found to be enhanced in individuals with a history of COVID-19.

How was the study conducted?

Sixteen individuals who had never previously been infected with SARS-CoV-2 and an additional 16 who were infected about nine months ago participated in the study. Blood was drawn from each individual both before and 21 days after mRNA vaccination to quantify the presence of RBD-specific antibodies.

Within the SARS-CoV-2 naive group, RBD-specific antibodies were not detected in pre-vaccinated sera, but at the second time point, all but one were significantly elevated anti-spiked protein immunoglobulin A. Had (IgA) and immunoglobulin G (IgG). , And mildly elevated immunoglobulin M (IgM). Upon vaccination, similarly elevated IgA and IgG levels were observed in both groups, but in this case the elevated IgM was less pronounced in those with SARS-CoV-2 experience.

Total Ig levels for RBD or peplomer are elevated in those who have experienced SARS-CoV-2 prior to vaccination, explaining a less noticeable increase in observed IgM levels. However, it should be noted that the pre-vaccination IgM levels of these individuals were on average higher than the post-vaccination IgM levels of SARS-CoV-2 naive individuals.

Cells were transfected with plasmids expressing various known SARS-CoV-2 peplomer variants along with other similar peplomers. Coronavirus.. Plasma samples from 32 participants were presented to the cells. As expected, the pre-vaccinated naive group did not contain anti-spike antibodies, but both the experienced and post-vaccinated groups did. Finally, an ELISA assay was performed to measure anti-full-peplomer antibody levels to assess whether the vaccine response was limited to the peplomer RBD. It was noted that after vaccination, the SARS-CoV-2 naive group induced similar levels of antibody as those observed in SARS-CoV-2 experienced individuals prior to vaccination.

Vaccinated SARS-CoV-2 naive individuals were able to recognize fewer mutants of peplomer compared to experienced SARS-CoV-2 individuals, both before and after vaccination. It was. However, vaccination of the latter group further increased immunity to the same SARS-CoV-2 peplomer beyond already high baseline levels.

Detection of SARS-CoV-2 spike mutants and other betacoronaviruses. (AI) From different SARS-CoV-2 variants and other human betacoronaviruses using plasma samples collected before and after the first dose of vaccination in SARS-CoV-2 naive and previously infected donors Cell surface staining of 293T cells expressing full-length spikes. .. The graph shows the median fluorescence intensity (MFI) obtained. The detection limit is plotted. (* P <0.05; ** P <0.01; *** P <0.001; **** P <0.0001; ns, not significant)

Is the vaccine effective?

The amount of anti-SARS-CoV-2 antibody in plasma returns to baseline levels relatively quickly in the host after viral attack. In fact, the presence of neutralizing antibodies was not observed to be significantly increased in naive individuals after vaccination.

However, antibody-dependent cellular cytotoxicity (ADCC) was found to increase significantly after vaccination and remain high.

Fc receptors are found on the surface of various immune cells, bind to antibodies attached to pathogens, stimulate phagocytosis or ADCC, and play an important role in immunity. Similar to the presence of anti-peplomer antibody, SARS-CoV-2 inexperienced individuals showed no ADCC activity prior to vaccination, but showed a significant increase after a single dose and SARS-CoV-2 prior to vaccination. It has reached the same level as an experienced person. Individual.

Often, T cells rely on antibodies that bind with high specificity to the relevant target. Effectiveness Between the two. IgA, IgG, and CD4 + T cell responses were found to be correlatedly elevated after vaccination, but IgM levels were only slightly elevated. The improved response observed in experienced individuals of SARS-CoV-2 compared to the naive group is that having an existing CD4 + T cell response is an effective humoral response to SARS-CoV-2. It is beneficial to development and suggests that these defenses can be further strengthened. By mRNA vaccine booster.

There was a significant increase in CD4 + T cell response after vaccination, especially in patients who had previously been infected with SARS-CoV-2. The CD8 + T cell response was also significantly increased after vaccination, but only in the SARS-CoV-2 experienced group and in the naive group there was only a slight increase in activity. Naive individuals with SARS-CoV-2 showed significantly increased IgG levels over IgM or IgA. Overall, vaccination elicited a response that was significantly similar to that of naive individuals, as was the case with past SARS-CoV-2 infections in others prior to vaccination. SARS-CoV-2 specific T cell immune responses were observed after vaccination in both groups, but more prominent in the experienced group, with naive individuals from the two vaccinations normally prescribed. It suggests that you will benefit more.

The study found that the applied Pfizer-BioNTech mRNA vaccine was up to 90% effective in a single dose 2 weeks after administration.

*Important Notices

bioRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.