Understanding Long-Lived Plasma Cells and Their Role in Vaccine-Induced Immunity

By SWA

Introduction

Vaccines are designed to stimulate the immune system, creating memory cells that provide protection against future infections. One critical component of long-term immunity is long-lived plasma cells (LLPCs), which reside primarily in the bone marrow and continuously produce antibodies. 

These cells are responsible for sustained immune protection, potentially lasting for years or even decades. Recent discussions have raised concerns about the durability of immunity provided by certain vaccines, particularly mRNA vaccines, and their ability to induce these LLPCs.

This article explores the role of LLPCs in vaccine-induced immunity and evaluates recent findings regarding different vaccine types, including the mRNA vaccines, in comparison to more traditional vaccines like the flu and tetanus vaccines.

Long-Lived Plasma Cells: The Cornerstone of Durable Immunity

Plasma cells are differentiated B cells that produce antibodies targeting specific antigens. After vaccination or infection, some of these plasma cells persist as long-lived plasma cells (LLPCs), mainly in the bone marrow, continuing to secrete antibodies even in the absence of the antigen. These cells are crucial for maintaining long-term immunity, as they ensure that the body retains the ability to fight off future encounters with the same pathogen without requiring a booster or re-exposure.

LLPCs in Traditional Vaccines

Several vaccines, such as those for influenza (flu) and tetanus, are known to elicit a strong and durable LLPC response. A study conducted by Slifka et al. (1998) found that antibody responses to vaccines like tetanus and measles can last for decades, sustained by LLPCs in the bone marrow [1]. Similarly, the flu vaccine has been shown to produce long-lived immunity, although this may vary depending on the specific strain and vaccine formulation used each year [2].

The mRNA Vaccines: A Closer Look

The mRNA vaccines, notably the Pfizer-BioNTech and Moderna COVID-19 vaccines, introduced a new technology to the vaccine landscape. While these vaccines have been highly effective in preventing severe disease and reducing transmission, there has been increasing interest in understanding the long-term durability of the immunity they provide, particularly in relation to LLPCs.

In a recent study (2021), Turner et al. observed that mRNA vaccines do elicit a strong initial antibody response. However, concerns have been raised regarding the long-term persistence of these antibodies and whether the vaccines generate adequate levels of LLPCs [3].

Evaluating the Data

In the image shared, a visual comparison of LLPC responses across different vaccines, including flu, tetanus, and mRNA (S2P), is shown. Over the course of 2.5 months, LLPCs were detected in individuals vaccinated with flu and tetanus vaccines, but the mRNA vaccine did not exhibit a similarly strong or durable response at later time points (14 and 23 months).

This suggests that while mRNA vaccines are highly effective in the short term, they may not induce the long-lived plasma cells required for prolonged immunity. This lack of LLPC generation could result in a decrease in immunity over time, necessitating booster doses to maintain protection.

Immune Response: Allergenic vs. Antigenic

The speaker in the shared image commentary makes an important distinction between two types of immune responses:

  • Antigenic Response: This is the desired immune response in which the immune system recognizes the vaccine's antigen, generates memory B and T cells, and forms long-lived plasma cells to provide long-lasting protection.
  • Allergenic Response: This refers to a more inflammatory reaction, where the immune system may produce antibodies in response to the vaccine, but the effect is more transient and may even lead to tolerance rather than robust immunity. Some researchers suggest that an IgG4 shift, seen in certain responses to the mRNA vaccines, may indicate a tolerance-like state rather than continued active immunity [4].

If mRNA vaccines are indeed eliciting a more allergenic response, as suggested by some, this could explain the lack of LLPC generation and the potential need for repeated boosters to maintain protective immunity.

Can mRNA Vaccines Be Considered Traditional Vaccines?

Given these findings, the question arises: Can mRNA vaccines be considered traditional vaccines in the sense of providing durable, long-lasting immunity? Vaccines like those for flu and tetanus clearly generate LLPCs and provide immunity that can last for years. In contrast, the mRNA vaccines may not provide the same long-lived immunity and might require frequent boosters to sustain protection.

Future Directions

Further research is needed to fully understand the mechanisms behind the immune responses generated by mRNA vaccines. Ongoing studies are examining how long antibody titers last, the persistence of memory B cells, and whether booster shots can enhance long-term protection.

Conclusion

Long-lived plasma cells are fundamental to the concept of durable immunity. While traditional vaccines like flu and tetanus have been proven to generate these cells effectively, concerns about the durability of the immune response to mRNA vaccines have emerged. The lack of LLPCs in individuals vaccinated with mRNA vaccines raises questions about the long-term immunity provided and highlights the potential need for ongoing booster shots. Understanding these differences is key to shaping vaccination strategies in the future.

References

  1. Slifka, M. K., et al. (1998). Humoral Immunity to Viruses: Antibody Levels and B-Cell Memory following Infection and Vaccination. Immunological Reviews. Link to study

  2. Ellebedy, A. H., et al. (2016). Flu Vaccines and Long-Lived Plasma Cells. Journal of Immunology. Link to study

  3. Turner, J. S., et al. (2021). mRNA Vaccines Induce Persistent Human Germinal Center Responses. Nature. Link to study

  4. Irrgang, P., et al. (2022). Class Switch Towards Non-Inflammatory, Spike-Specific IgG4 Antibodies after Repeated SARS-CoV-2 mRNA Vaccination. Science Immunology. Link to study

By understanding the role of LLPCs in vaccine-induced immunity, we can better assess how different vaccines perform and inform future public health strategies for long-term protection against infectious diseases.

 © 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right.
Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9

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