How does SARS-CoV-2 infection and vaccination affect immunological memory in humans?

Severe acute respiratory coronavirus 2 (SARS-CoV-2) coronavirus family Families are the causative agents of the coronavirus disease 2019 (COVID-19) pandemic, with more than 600 million recorded infections that have killed more than 6.5 million people.

SARS-CoV-2 is closely related to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), both of which caused epidemics in 2002-2003 and 2013-2014, respectively. associated with significant morbidity. Human infections have also been reported from other areas. coronavirusOC43, 229E, NL63, HKU1, etc. Most appear as common seasonal colds.

study: New insights into human immune memory from SARS-CoV-2 infection and vaccination. Image Credit: Kateryna Kon / Shutterstock.com

Background

SARS-CoV-2 enters the host by binding to the angiotensin-converting enzyme 2 (ACE2) receptor on the surface of host cells via a receptor-binding domain (RBD) within the virus. spike proteinACE2 receptors are present on cells of the respiratory tract, gastrointestinal tract, heart, and kidneys.

Most people infected with SARS-CoV-2 experience mild respiratory symptoms. However, patients with pre-existing comorbidities such as chronic obstructive respiratory disease (COPD), obesity, asthma, and immunocompromised patients are at increased risk of severe her COVID-19. For example, individuals with increased ACE2 expression or compromised immune function have higher viral load, greater infectivity, and poorer viral control.

Scientists have studied the human immune response to SARS-CoV-2 infection. Recently developed techniques can detect, quantify, and phenotype immune memory cells. The emergence of worrying SARS-CoV-2 variants (VOCs) has highlighted the need for biomarkers that can quantify the protection conferred by his COVID-19 vaccine based on the original Wuhan strain.

Recent allergy A journal study reviews current knowledge on the generation of immune memory responses and their persistence after infection and vaccination. Researchers also provide insights into immunological memory for its ability to protect against emerging VOCs.

Methods for detecting SARS-CoV-2 immune memory cells

The adaptive immune system primarily relies on the action of both T and B cells to elicit antigen-dependent and antigen-specific responses. After infection or vaccination, B and T cells that recognize pathogens from previous exposure respond, proliferate, and differentiate.

Cells of the adaptive immune system thus allow the development of immune memory comparable to innate immune responses that have no memory capacity. The cells responsible for this subsequent response are memory B cells (Bmem) and memory T cells (Tmem).

Bmem is traditionally detected using enzyme-linked immunosorbent spotting (ELISPOT), a highly sensitive and rapid technique. Despite these advantages, ELISPOT is a time-consuming process and does not provide information on isolated her B cells that do not recognize the antigen of interest.

Another approach that can be used to determine antigen reactivity of Bmem or plasma cells is the immortalization of B cell clones. This identifies antibodies produced by a single her B cell clone. However, this method is often time-consuming and labor-intensive, limiting its applicability in certain settings.

Antigen-specific B cells can also be identified by labeling antigens of interest and subsequently probing the cells for reactivity to these antigens. This approach allows a thorough examination of the immunophenotype of these cells and also allows researchers to collect cells at the end of the experiment for further analysis.

Compared to B cell analysis, the assessment of SARS-CoV-2-specific T cells is more difficult as they only recognize peptide fragments of the original antigen. Researchers therefore use a variety of assays to detect antigen-specific CD8+ and CD4+ T cells.

Antigen-specific T cells are developed by stimulating peripheral blood mononuclear cells (PBMCs) with whole-protein antigens and determining the various T cells generated by this reaction, as indicated by specific activation markers. can also be evaluated. These include intracellular cytokines such as interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ).

Antibody response to SARS-CoV-2

Seven to ten days after SARS-CoV-2 infects cells, activated B cells differentiate into plasmablasts. These plasmablasts then induce the production of antibodies that typically target the SARS-CoV-2 spike and nucleocapsid proteins by 20 days post-infection.

quantification of Neutralizing antibody (nAbs) are often used to reflect previous SARS-CoV-2 infections. After infection or vaccination, these nAbs remain stable for at least 3 months, and some antibody levels persist up to 8-15 months after the initial antibody response.

Bmem circulation has also been used to assess the trajectory of COVID-19. Early in SARS-CoV-2 infection, Bmem normally expresses immunoglobulin M (IgM) and then shifts to CD21 expression.

Up to 11 months after infection, Bmem switches to IgG at increasing levels. Moreover, her Bmem levels of CD27+ and CD71− may remain stable for more than 12 months after infection, indicating a sustained B-cell memory response.

Various SARS-CoV-2-specific T cells have been characterized, including CD8+ and CD4+ effector and memory subsets, and T helper cells (Tfh). Both CD4+ T cell and Tfh cell responses remain stable for approximately 1 month after infection, whereas CD8+ T cells remain detectable in 70-80% of convalescent samples at this time point.

These T cell responses remain detectable up to 8 months post-infection. However, unlike Bmem, Tmem levels typically decline over time.

immune response to vaccination

Adenoviral vector and messenger ribonucleic acid (mRNA) COVID-19 vaccines were rapidly developed after the outbreak of the pandemic and subsequently approved in many countries around the world. These two COVID-19 vaccines are designed to generate both humoral and cellular responses to the SARS-CoV-2 spike protein.

High levels of nAbs are detected 4 weeks after administration of both adenoviral and mRNA vaccines, with convalescent individuals producing much higher antibody levels compared with post-vaccination naive individuals . Plasma cells produced after mRNA vaccination have been detected for up to 7 months.

Compared to mRNA vaccines, adenoviral vaccines produce significantly lower IgG and nAbs. Antibody levels appear to peak 15-20 days after mRNA vaccination, followed by a decline in nAb levels.

SARS-CoV-2 spike-specific Bmem was produced following a peak of one mRNA vaccine dose 1 month after the second vaccine dose. Interestingly, convalescent individuals produce higher Bmem levels in response to initial mRNA vaccination compared with naive individuals due to pre-existing infection-induced immune memory cells. Nonetheless, infection-naive individuals produce detectable spike-specific Bmem for up to 6 months after the second mRNA vaccination.

Spike-specific CD4+ and CD8+ T cells also appear to peak within the first 4 weeks after completing the two-dose mRNA vaccine series. However, compared with the stable Bmem levels reported after vaccination, CD4+ and CD8+ T cell levels appear to decline 3 months after vaccination.

Immunity to SARS-CoV-2 VOCs

Several of the SARS-CoV-2 variants (VOCs) of concern have been reported to be highly contagious, likely to cause severe disease, and capable of evading vaccination immunity.

A third booster dose, 3-6 months after the first vaccination, is recommended in some countries to address the loss of protection from vaccination against these VOCs. Additionally, booster vaccination has been shown to respond to Bmem, thus increasing the production of nAbs that bind and neutralize the SARS-CoV-2 VOC.

Conclusion

Strong efforts to understand the immune memory induced after COVID-19 vaccination and/or SARS-CoV-2 infection and the persistence of these responses could be a future therapeutic strategy for treating vulnerable individuals. to help you design. Clinical assays that can identify Tmem and Bmem allow researchers to assess vaccine efficacy to determine the need and timing of subsequent booster doses.

Further research is needed to determine the ability of immunological memory to recognize VOCs and protect against infection and severe COVID-19 and associated mortality. Taken together, these efforts will help fight the ongoing COVID-19 pandemic.