Durability of cellular immune memory to SARS-CoV-2 after mRNA vaccination

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread rapidly. However, vaccines are now playing a significant role in mitigating viral spread. SARS-CoV-2 messenger RNA (mRNA) vaccines teach our cells how to make a protein that triggers an immune response inside our bodies. That immune response, which produces antibodies, protects us from getting infected if the actual virus enters our bodies.

Clinical trial data for both mRNA vaccines demonstrate up to 95% efficacy in preventing symptomatic coronavirus disease 2019 (COVID-19). The mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination.       

A recent study, available on the bioRxiv* preprint server, investigated the durability of cellular immune memory after mRNA vaccination against SARS-CoV-2 and whether booster jabs affect the durability of different immune response components. The study included testing for antibodies and cellular immune responses in covid patients and recovered individuals.

The study

In a set of test-tube experiments from 61 fully vaccinated individuals, the maintenance of the immune response was monitored from pre-vaccination to six months post-vaccination. Within this cohort, two groups were created; those who had been previously infected with SARS-CoV-2 and those who were naïve to the virus.   

The researchers found that the antibody and neutralizing titers had degraded from peak levels but were undetectable in all the participants at six months post-vaccination. It was also observed that the mRNA vaccination generated functional memory B cell responses, including those that were specific for the receptor-binding domain (RBD) of the Alpha, Beta, and Delta variants. The vaccination was also recognized to continue its effect between three to six months post-vaccination.

Distinctly, most memory B cells induced by mRNA vaccines were capable of cross-binding variants of concern. B cell receptor sequencing exhibited significantly more hypermutation in these RBD variant binding clones than in clones that particularly bound wild-type RBD. Moreover, the percentage of variant cross-binding memory B cells was higher in vaccinees than individuals who recovered from mild COVID-19.

mRNA vaccination also generated antigen-specific CD8+ T cells and long-lasting memory CD4+ T cells in most participants, with early CD4+ T cell responses interacting with humoral immunity at later stages. These findings showed robust, multi-component humoral and cellular immune memory to SARS-CoV-2 and other variants of concern for at least six months after mRNA vaccination.

The experts conclusively recognized that a  booster dose of pre-existing immunity with mRNA vaccination in participants who had recovered from COVID-19 essentially increased their antibody responses in a short period without significantly changing antibody decline rates or long-term B and T cell memory. Thus, immunity was not hampered. It was rather improved with the introduction of the vaccine. Moreover, this longitudinal study provided insights into the formation and evolution of vaccine-induced immunity to COVID-19, including concerned variants, and has indications for future plans of booster doses of the vaccine.


In conclusion, the study illustrated that mRNA vaccines incite durable immunity memory to SARS-CoV-2 infection, which proceeds to develop over time. Precisely, the analyses showed that SARS-CoV-2 specific memory B cell responses were robustly produced following mRNA vaccination and continued to progress in incidence for at least six months, despite a decline in circulating antibody levels in the same participants. The study found that booster vaccination did not improve cellular immune memory; rather, it transiently increased antibody levels.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Rashika Tripathi

Written by

Rashika Tripathi

Rashika Tripathi is a dental graduate from Bangalore, India. She first took an interest in medical communications when she started her health and lifestyle website. She went on to do various research in her field and worked as a research assistant. Thus, she grew in her profession, not just in clinical terms but also in the academic research base. Rashika worked as a freelance medical writer for various firms and hospitals and helped to expand their content.


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