Full COVID-19 mRNA Vaccination Course Induces Long-Term Antibody, Memory B-Cell Response

Following a full 3-dose mRNA vaccination against SARS-CoV-2, the virus that causes COVID-19, health care workers with distinct exposure histories developed durable, sustained B-cell and antibody responses over a 3-year period, with participants retaining a significant SARS-CoV-2-reactive memory B-cell (MBC) pool that prevented breakthrough infections in naïve participants, according to data published by investigators in Cell Reports.^1,2

mRNA COVID-19 vaccines effectively induces long-term memory B-cells and antibody development. | Image Credit: © Matthieu - stock.adobe.com

The results provide valuable evidence for the long-term effectiveness of COVID-19 mRNA vaccination. Notably, the data suggests that previously infected participants not only had comparable humoral responses 17 months after a full vaccination course, but they also developed an expanded SARS-CoV-2-reactive CD27⁻CD21⁻ atypical B-cell population that remained stable throughout the follow-up period, according to the authors.^1,2

Long-Term Studies of mRNA Vaccine Effectiveness are Crucial

COVID-19 mRNA vaccines have been proven effective in reducing transmission, but as variants of the virus have emerged, the vaccine has been hampered by reduced effectiveness against currently circulating strains. The study authors note the crucial nature of long-term studies of vaccine effectiveness to better guide physicians and pharmacists when they provide vaccine recommendations to patients.^1,2

To examine the kinetics of the antibody and MBC response to SARS-CoV-2 infection and mRNA vaccination, the current investigators examined the CovidCatCentral study. The study analyzed a longitudinal subset of 113 volunteers from a cohort of health care workers in central Catalonia, Spain. The study authors, including senior co-author Gemma Moncunill, sought to determine the full scope of MBCs in patients who received a COVID-19 mRNA vaccination, as these cells are critical for sustaining long-term immunity.^1,2

“There is the belief that vaccine-induced antibodies to SARS-CoV-2 decay rather rapidly, but recent evidence suggests that they remain quite stable over time,” Moncunill said in an accompanying news release.²

Participants were stratified into those naïve to COVID-19 (n = 65) and those previously exposed (n = 48) prior to primary vaccination, and all participants were vaccinated with a full, 3-dose COVID-19 vaccine regimen. Peripheral blood mononuclear cells (PBMCs) and plasma were collected at 5 months post-second dose, 5 months post-third dose, and 17 months post-third dose.^1,3

Memory B Cell Responses Observed at 17 Months in Exposed and Non-Exposed Participants

By 17 months after receiving a third vaccine dose, immunoglobulin G (IgG) antibody levels were observed to be comparable between each group and were stable in non-exposed subjects while slightly decaying in exposed patients. Despite the slight decline in IgG response observed, it remained above the response measured following primary vaccination and was restored upon receiving a vaccine booster.¹

Study authors found that SARS-CoV-2-reactive MBCs can be long-lasting and expand towards receptor-binding domain (RBD) recognition following the 3-dose vaccination course. They found stabilized humoral responses at 5 months following the third dose, which were significant predictors of long-term immunity. Importantly, these measurements of viral protection were again at similar magnitudes between the exposed and non-exposed groups, even despite the differential kinetics and coordination of humoral response between each participant.¹

At 5 months post-third dose, there were breakthrough infection episodes (BTE) confirmed in 29% (n = 14) and 37% (n = 24) of exposed and nonexposed subjects, respectively. The investigators also examined whether the incidence of BTEs impacted the development of durable SARS-CoV-2-reactive MBCs. In this regard, they found that exposed individuals with BTE had an increase in RBD MBC frequencies by 5 months post-third dose compared with those without a BTE. Overall, they found that infection with SARS-CoV-2 following a 3-dose mRNA vaccination helps shape the humoral response of non-exposed subjects.¹

“Over time, we saw a progressive increase in the proportion of memory B cells recognizing the RBD of the spike protein, pointing to their continuous selection upon exposure to evolving variants,” Luis Molinos-Albert, lead author of the study, said in an accompanying news release.²

As new data continues to emerge and further investigations are initiated into the long-term effectiveness of COVID-19 vaccines, pharmacists should stay aware and be prepared to counsel their patients as to any evidence-based shifts in guidelines. At this point, data reflects the long-term effectiveness of mRNA vaccines targeting SARS-CoV-2, meaning key at-risk populations, including health care workers, can be assured of their protection.

REFERENCES

1. Molinos-Albert LM, Rubio R, Martin-Perez C, et al. Long-lasting antibody B-cell responses to SARS-CoV-2 three years after the onset of the pandemic. Cell Reports. 2025;44(4):115498. doi:10.1016/j.celrep.2025.115498

2. ISGlobal Barcelona Institute for Global Health. COVID-19 vaccination induces long-lasting antibody B-cell responses. News Release. Released April 8, 2025. Accessed April 23, 2025. https://www.isglobal.org/en/-/vacunacion-covid-19-y-celulas-b-memoria

3. Ramirez-Morros A, Alonso S, Ruiz-Olalla G, et al. Eleven-month longitudinal study of antibodies in SARS-CoV-2 exposed and naïve primary health care workers upon COVID-19 vaccination. Immunology. 2022. doi:10.1111/imm.13551