Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection with SARS-CoV-2 results in a B-cell response that lasts for at least a year. Therefore, immunological memory is essential to prevent reinfection, and B cells play an important role in this aspect of the defense mechanism provided by the immune system.
B cell memory develops in response to infections and vaccinations. The rapid recall response evoked by Memory B cells helps provide long-term protection against pathogens.
New research published in the journal Nature I tried to investigate the evolution of memory B cells 5 months after vaccination with mRNA vaccines such as Moderna (mRNA-1273) and Pfizer-BioNTech (BNT162b2) in SARS-CoV-2 inexperienced people. This study investigated various aspects of Memory B cell antibody response, including neutralization response, affinity, epitope targeting, and neutralization range.
The study recruited 32 volunteers with no history of SARS-CoV-2 infection who received either the two mRNA vaccines Moderna or Pfizer-BioNTech.
Blood samples were sequentially collected from 8 subjects who received Moderna and 24 subjects who were treated with Pfizer-BioNTech. Samples were collected from the study subjects on average 2.5 weeks after the first dose and identified as “prime”.
Similarly, samples were collected from subjects who received a second vaccination and completed the vaccination program. Individuals in this group were sampled at two time points. One averages 1.3 months and the other is about 5 months after booster immunization. The age of the study population ranged from 23 to 78 years, with a median age of 34.5, with 53% of the population being male and 47% being female.
Significant increase in plasma neutralizing activity in naive individuals receiving the COVID-19 mRNA vaccine
Perform ELISA (enzyme-linked immunosorbent assay) to determine the response of plasma immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA) to the SARS-CoV-2 receptor binding domain (RBD). I evaluated it.
This study showed that a significant increase in IgG responsiveness to RBD was detected during the period between administration of the prime and booster vaccines. This correlated with previous evidence.
After booster administration, the levels of IgM and IgA titers were found to be lower when compared to IgG. A significant inverse correlation was identified between response magnitude and age after prime vaccine administration. However, this correlation was not significantly detected in this small study population 1.3 or 5 months after booster immunization. In addition, IgG and IgA titers for RBD were significantly reduced between 1.3 and 5 months after booster immunization. In the case of IgG titers, a 4.3-fold decrease was observed, and the decrease in their activity showed a significant direct correlation with the time after vaccination.
HIV-1 pseudotyped with SARS-CoV-2 spikes was adopted to assess neutralizing activity. A significant inverse correlation was observed between age and neutralizing activity in naive individuals who received the first vaccine.
In the study population receiving booster doses, there was a similar 12-fold increase in neutralizing activity that did not vary by gender or age. In addition, a significant positive correlation was observed in the binding and neutralizing activity between the booster dose and the initial vaccine dose.
Naive individuals who received booster had 4.9 and 3.6 times higher neutralization titers 1.3 and 5 months after booster than those evaluated 1.3 and 5 months after the onset of COVID-19 symptoms. It turned out that it showed.
The results of this study suggest a significant increase in plasma neutralizing activity in naive individuals vaccinated with the COVID-19 vaccine, which correlates with the enhanced vaccine. Effectiveness After administration of booster. In addition, higher neutralization titers were observed in individuals who completed the vaccination regimen when compared to individuals infected with COVID-19.
Evaluating 28 subjects 5 months after booster administration, it was confirmed that neutralizing activity was inversely correlated with time and directly correlated with IgG anti-RBD binding titers. As previously reported, 1.3 months after booster immunization, binding to neutralized serum titers was higher in vaccinated individuals when compared to convalescent patients, but this difference in efficacy. Disappeared at a later time interval.
Similar to previous reports, the neutralizing activity for the tested variants was found to be lower when compared to the original Wuhan Hu-1 strain. Furthermore, it was found that as the time from vaccination increased further, the neutralizing activity also decreased relative to the original and mutant strains.
Memory B cells may continue to evolve for up to 5 months after COVID-19 mRNA vaccination
The effect of the mRNA vaccine on the Memory B cell compartment was assessed by flow cytometry. Flow cytometry measures B cells that express receptors that promote binding to Wuhan Hu-1 (wild type, WT) and B.1.351 K417N / E484K / N501Y variant RBDs. Memory B cells expressing the Wuhan-Hu RBD receptor were detected after the first mRNA vaccination and their numbers continued to increase 5 months after vaccination.
Memory B cells expressing the receptor for binding to the RBD of the mutant tested were detected at very low levels compared to wild-type. An increase in IgG memory cells was observed after the booster administration, but the first increase in IgM-expressing memory B cells after the prime vaccine administration was almost absent after the booster administration.
The plasmablasts were antibody-producing stem cells, and RBD-specific plasmablasts were detected after the first vaccine and significantly after booster immunization.
The memory compartment is known to evolve for up to one year after spontaneous infection, resulting in an enrichment of cells that produce antibodies that are effective against pathogens. This study examined the characteristics of memory compartments after mRNA vaccination.
The 2,327 pairs of antibody sequences from 11 individuals obtained at the time already described in the study were examined. IGHV3-30 and IGHV3-53 were epidemic after prime and booster administration and continued to be epidemic for 5 months after vaccination. Expanded clones of Memory B cells expressing the IGHV and IGHL genes were observed in all individuals studied.
The study found that the amount of memory cells varied between the initial dose of the vaccine, the booster dose, and the individual and decreased over time. Detection of unique clones in vaccinated individuals suggests that memory cells evolve for up to 5 months after vaccination.
It was also observed that memory cells isolated after booster administration had significantly higher levels of somatic mutations when compared to plasmablasts and B cells obtained after the first vaccination. This study shows that memory B cells may continue to mutate or evolve for 5 months after booster immunization after mRNA vaccination.
An additional immune dose of the COVID-19 mRNA vaccine enhances the neutralization response of antibodies expressed in the memory compartment.
ELISA was performed to assess the neutralizing activity of antibodies isolated from Memory B cells that bind to RBD. 458 antibodies were tested and 94% of the antibodies showed binding to Wuhan Hu-1 RBD, confirming the efficiency of the method used to isolate RBD-specific memory B cells. Geometric mean ELISA semi-maximum concentrations (EC50) of the antibodies obtained at various time points were estimated and there was no significant difference in the binding of these antibodies at the time of testing. The EC50s of the antibodies from the prime samples obtained 1.3 months and 5 months after the second dose were 3.5, 2.9, and 2.7 ng / ml, respectively.
The neutralizing activity of 430 RBD-binding antibodies was assessed using HIV-1 pseudotyped with SARS-CoV-2 spikes.The geometric mean semi-maximum inhibitory concentration (IC50) of the antibodies tested was increased from 376 ng / mL after the first vaccination to 153 ng / mL after the second vaccination, and this increase in activity was non-existent.Neutralizing antibody Increase in neutralizing antibodies.
Memory B cells recruited after the second dose of mRNA vaccine are involved in the enhancement of neutralizing activity observed between the first and second doses. The additional immune dose of the mRNA vaccine results in an improved neutralization response of the antibody expressed in the storage compartment.
The neutralizing activity of the obtained monoclonal activity was not significantly enhanced 1.3-5 months after vaccination. Interestingly, in convalescent individuals, antibodies from memory cells showed enhanced activity between 1.33 and 6.2 months after the onset of symptoms, with further improvement observed 1 year after the onset of symptoms. .. This was due to the increased neutralizing activity of the persistent clones.
Memory antibodies from convalescent individuals show improved post-infection affinity and neutralization margins compared to COVID-19 mRNA vaccination.ns
Affinity maturation was evaluated by performing biolayer interferometry (BLI) analysis using Wuhan Hu-1RBD. This is the process by which the immune system produces antibodies with increased affinity during the immune response. Antibodies were obtained 1.3 months and 5 months after booster immunization after the first dose, for a total of 147 antibodies.
Comparing the affinities of the antibodies, there is a 3-fold difference in the affinity of the prime obtained after booster administration and the antibody obtained at 1.3 months, and the affinity between the antibody 1.3 months and 5 months after booster immunization is 7.5. It turns out that there is a double difference.
The affinity of antibody pairs from persistent clones obtained 1.3 and 5 months after booster showed a 4.5-fold increase in affinity, whereas in convalescent individuals it was obtained 1.3 and 6.2 months after onset of symptoms. Antibodies from the persistent clones obtained have an affinity that shows a 11.2-fold increase.
The study also investigated whether there were changes in the target epitopes of monoclonal antibodies. It was found that there was no significant change in the epitopes targeted by the 52 antibodies studied, which were obtained 1.3 and 5 months after vaccination and showed similar neutralizing activity.
In convalescent individuals, the neutralization range of antibodies from memory cells has been found to increase with efficacy over time. The neutralizing ability of the prime and the antibody obtained 1.3 months after vaccination was tested against a pseudo-panel encoding the RBD mutation. It was found that there was a slight change in width and increased resistance to replacement of K417N and A475V. It was found that neutralized respiration was slightly increased during the post-vaccination period of the mRNA vaccine when compared to a similar period after COVID-19 infection in convalescent individuals.
The results of this study suggest that providing an additional immune dose of mRNA vaccine to vaccinated individuals increases plasma neutralizing activity. However, as observed in convalescent individuals, they may not produce antibodies that show a neutralization range against the variant of concern.
Convalescent individuals, when boosted with the mRNA vaccine, develop strong defenses against the original Wuhan-Hu-1 strain and the variant of concern.
Further investigation will focus on whether additional booster immunization with Wuhan-Hu-1 based or variant-based vaccines or reinfection results in memory B cells that may produce antibodies that exhibit increased neutralization. You need to hit.
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