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.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

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.

Conclusion

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.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Journal references:

Article Revisions

  • Apr 12 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
Rashika Tripathi

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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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