Study: Memory B Cells and Memory T Cells Induced by SARS-CoV-2 Booster Vaccination or Infection Show Different Dynamics and Responsiveness to the Omicron Variant Image Credit: Juan Gaertner / Shutterstock

Memory B and T cell responses differ when induced by SARS-CoV-2 infections or booster vaccines

In a recently published study Journal of ImmunologyA research team from Japan, studied memory B and T cell responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein after a booster dose of coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA). ) Inoculate BNT162b2. They also evaluated the cross-reactivity of memory B and T cell to the Omicron variant.

Studies: Memory B Cells and Memory T Cells Caused by SARS-CoV-2 Booster Vaccination or Infection Show Different Dynamics and Sensitivity to the Omicron Variant Image Credit: Juan Gaertner/Shutterstock

Background

The rapid development of various vaccines has successfully limited the severity and mortality rates of COVID-19. However, serum neutralizing antibody titers from vaccines and previous SARS-CoV-2 infections decreased over time.

The emergence of SARS-CoV-2 variants carrying mutations in the spike protein that increase their transmissibility and ability to evade immunity has raised concerns about reduced immunity. Currently circulating SARS-CoV-2 Omicron variants and sub-variants carry mutations in the receptor-binding domain (RBD) of spike proteins, allowing them to evade neutralizing antibodies from vaccines.

Although research shows that booster doses can provide sustained protection against severe COVID-19, immune responses differ between individuals. Also, the persistence of memory B and T cell responses has not been extensively investigated.

about the study

This study included 43 healthy individuals with no history of autoimmune, liver, kidney, or systemic disease, cancer, or diabetes. The study also included 88 COVID-19 patients diagnosed with a positive reverse transcription polymerase chain reaction (RT-PCR) test. Healthy subjects were vaccinated with two primary doses of BNT162b2 vaccine and a third (boost) dose eight months after the second dose.

Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples of all individuals. Complete spike protein and RBD were generated, and the purity and concentration of the proteins were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and protein assays.

Enzyme-linked immunospot (ELISpot) assay was used to detect memory B cells secreting anti-RBD antibodies. Memory T cell response was measured using the interferon-gamma (IFN-γ) ELISpot assay and fluorescence-activated cell sorting (FACS) for detection.

Activation-induced marker (AIM) presenting circulating follicular T helper cells after stimulating PBMCs for one to two days with the SARS-CoV-2 spike protein.

In addition, PBMCs were cultured with SARS-CoV-2 spike protein in the presence of interleukin-2 (IL-2) to produce anti-RBD antibodies. in a laboratory settingconcentration was measured using the enzyme-linked immunosorbent assay (ELISA). The researchers also measured the cross-reactivity of memory B and T cells to the SARS-CoV-2 Omicron variant using the IFN-γ ELISpot assay and FACS.

Results

The results reported that neutralizing antibodies to the SARS-CoV-2 spike protein RBD decreased, memory B cells increased, and memory T cell numbers gradually decreased in the months following vaccination. However, with the third dose of the vaccine, memory B cell levels rose further, while neutralizing antibody and memory T cell levels returned to post-second vaccine dose levels.

In the cross-reactivity test to Omicron variant RBD, memory T cells showed a similar response to the ancestral Wuhan strain, while memory B cells showed reduced avidity despite 60-80% binding to Omicron RBD. However, the authors believe that the normal T cell response to the Omicron variant indicates that affinity maturation induced against the Omicron spike protein will provide adequate protection against infections with the Omicron variant.

When immune responses from SARS-CoV-2 infections were compared with those from vaccines, the results showed that infections resulted in higher memory T cell levels but lower memory B cell levels. Unlike other studies, this study also found that patients with moderate disease symptoms elicited the strongest memory B and T cell responses.

The authors also speculated on possible reasons to explain the increased memory B cell levels after vaccination with BNT162b2. They believe that the high level of spike protein produced due to the mRNA vaccine causes B cells to continue to differentiate into plasma cells even three weeks after vaccination.

solution

Overall, the results showed that the memory B and T cell responses induced by the booster dose of the mRNA vaccine differed from those induced by SARS-CoV-2 infection, with vaccinations eliciting a higher memory B cell response and a lower memory T cell response. . .

In addition, memory B cells showed sufficient binding affinity to the RBD of the SARS-CoV-2 Omicron variant, whereas binding avidity was low. However, memory T cells exhibited similar activity against the Omicron variant to the Wuhan strain, conferring protection against Omicron infections.

Journal reference:

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