T cells from prior coronavirus protects and nucleocapsid directed COVID-19 shots may work better

This article highlights a peer-reviewed study from the Imperial College of London. [1] The research answers the question, Why is it that not all people exposed to SARS-CoV-2 develop the disease? Is it possible that a previous illness from another coronavirus can protect against the SARS-CoV-2 virus? Is there a better alternative to spike-based vaccines?

As a background, there are four seasonal coronaviruses that circulate and cause 11-41% of respiratory tract infections every year. They are the NL63, 229E, OC43, and HKU1. All of them share similarities to the SARS-CoV-2 virus, the cause of COVID-19/

Coronavirus proteins

All coronaviruses have similar structures and proteins. The spike (S), membrane (M), envelope (E), and nucleocapsid (N) proteins are the major ones.

By: SPQR10

In an infection, the body develops an immune response (antibodies, T cells, and B cells) against parts of the coronavirus. Those parts are called epitopes.

Similarities among the OC43, HKU1, and SARS-CoV-2

The recently published investigation compared the different known epitopes from the three beta coronaviruses SARS-CoV-2, OC43, and HKU1 to see if they share any T cells that are the same. The beta here is different from the SARS-CoV-2 Beta variant.

The epitope similarities are presented in the figure below.

The three inner colored circles represent the three viruses, and the multicolored outermost circle represents the different proteins Spike (S), Membrane (M), Nucleocapsid (N), and Envelope (E).

The red bars across the three viruses represent the cross-reactive epitopes in the nucleocapsid and spike proteins.

Source: Kundu et al, 2022

Cross-reactive epitopes are present in all three viruses. As previously mentioned, epitopes elicit immune responses from T cells or T lymphocytes.

T lymphocytes are white blood cells necessary to fight viral infections. Cross-reactive T cells produced from a previous OC43 or HKU1 coronavirus infection can react with the same matching epitope in the SARS-CoV2 virus and provide protection.

Study Participants

Fifty-two people who had never had COVID-19 before were analyzed. All of them were recently exposed to someone with COVID-19. 26 of them later became SARS-CoV-2 PCR positive, and 26 continued to be PCR negative.

Results

The 26 PCR negative had detectable cross-reactive T cells within six days, which means that they are pre-existing, while the T cells in the PCR positives increased after ten days which is the typical duration in a new infection.

The protection provided by pre-existing cross-reactive T cells from a previous HKU1 or OC43 coronavirus infection may explain why the 26 people exposed to COVID-19 tested negative for SARS-CoV-2.

T cells against nucleocapsids work

The T cells produced interleukin-2 (IL-2) in response to the nucleocapsid proteins. IL-2 stimulates the growth and production of immune cells like the B cells and T cells. IL-2 producing T cells in the PCR negative group protected them against a SARS-CoV-2 infection.

Furthermore, T cells with interleukin-2 can expand into interferon-gamma (INF-γ), secreting T cells. IF-γ activates immune response genes and recruits other white blood cells like macrophages, neutrophils, and natural killer cells.

Their findings about the IF-γ are similar to another study [2] that showed some health care workers are protected by their T cells despite frequent exposure to SARS-CoV-2. You can read about it at Pre-existing T-cells stop COVID-19 before it starts and explain why some never get COVID.

Cross-reactive T cells against the spike protein have limited protection

Interestingly, the cross-reactive T cells directed against the spike protein are not associated with higher production of IL-2, which hints that they have a limited protective function.

Significance

The study published in Nature magazine illustrates that prior seasonal coronavirus infections can confer protection against SARS-CoV-2 thru the production of T cells.

New variants like the Omicron with multiple mutations in their spike protein can evade antibodies from prior COVID shots. The authors suggest that nucleocapsid-based vaccines against COVID-19 should be considered for future vaccines, and this may prevent immune evasion that we are seeing now in spike-based vaccines.

Non-spike protein-based shots can prevent the adverse reactions related to SARS-CoV-2 spike protein exposure. 13 ways that the SARS-CoV-2 spike protein causes damage.

In summary, T cells developed from previous seasonal coronavirus infections confer protection against the SARS-CoV-2.

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Related:

  1. T cells from previous infections and shots are protective against the Omicron variant
  2. People who recovered from COVID-19 have effective T-cells against the Omicron.
  3. Ten Studies showing a low risk of COVID-19 reinfection among unvaccinated
  4. Asymptomatic or mild symptomatic COVID-19 elicits effective and long-lasting antibody responses in children and adolescents
  5. Can coronaviruses elicit long-lasting immunity?
  6. 60% may already have Immunity to COVID-19
  7. Pre-Existing T-Cells Stop COVID-19 Before it Starts
  8. Harvard: Immunity from mild COVID-19 infection much better than vaccination
  9. Natural Immunity Protected Tanzania and Zambia from COVID-19
  10. CD4+ Cross-Reactivity between Seasonal Coronavirus Colds and COVID-19

References:

  1. Kundu, R., Narean, J.S., Wang, L. et al. Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts. Nat Commun 13, 80 (2022). https://doi.org/10.1038/s41467-021-27674-x
  2. Swadling, L., Diniz, M.O., Schmidt, N.M. et al. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2Nature (2021). https://doi.org/10.1038/s41586-021-04186-8

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2 Replies to “T cells from prior coronavirus protects and nucleocapsid directed COVID-19 shots may work better”

    1. I will give the manufacturers the benefit of the doubt. There was not much information about the spike proteins’ adverse effects when the current vaccines were designed. But now that there is scientific literature about the spike protein’s effects and the number of adverse events and deaths temporally associated with the shots that are enough to prove causality, those shots should be stopped.

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