#MSCOVID19 Vaccine Readiness. Development the case for the T and the B cells

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We are still pinning our hopes on a COVID-19 vaccine, as it stutters due to case of neurological problems with the Oxford vaccine.

We have made the case that the innate and the T cell responses can deal with the virus and this is further supported here. So people who deal with the virus and remain asymoptomatic, don’t seem to make much of a B cell response. However, if the virus escapes then those viral specific B cells may become important. We know that B cell depletion can blunt the anti-viral response but if the T cells are active this may be enough. So this is food for thought, if you are concerned about B cell depleting agents

The dichotomous and incomplete adaptive immunity in COVID-19Gao, L., Zhou, J., Yang, S., Chen, X., Yang, Y., Li, R., Pan, Z., Zhao, J., Li, Z., Huang, Q., Tang, J., Hu, L., Liu, P., Zhang, G., Chen, Y., Ye, L.10.1101/2020.09.05.20187435 

Asymptomatic patients have been found to induce weak and transient SARS-CoV-2 antibody responses. Meanwhile, the protective immunity that guide the recovery of these asymptomatic patients is also not well studied. Here, we characterized SARS-CoV-2-specific B-cell and T-cell responses in 10 asymptomatic patients and 49 patients with other disease severity (mild, n=10, moderate, n=32, severe, n=7) and found that asymptomatic or mild symptomatic patients failed to mount virus-specific germinal center (GC) B cell responses that result in robust and long-term humoral immunity, assessed by GC response indicators including follicular helper T (TFH) cell and memory B cell responses as well as serum CXCL13 levels. Alternatively, these patients mounted potent virus-specific TH1 and CD8+ T cell responses. In sharp contrast, patients of moderate or severe disease induced vigorous virus-specific GC B cell responses and associated TFH responses; however, the virus-specific TH1 and CD8+ T cells were minimally induced in these patients. These results therefore uncovered the protective immunity in asymptomatic patients and revealed the strikingly dichotomous and unbalanced humoral and cellular immune responses in COVID-19 patients with different disease severity, providing important insights into rational design of COVID-19 vaccines.

Yet more evidence that the T cell response is key in the early response

More memory B cells are associated with more antibodies

Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom durationNewell, K. L., Clemmer, D. C., Cox, J. B., Kayode, Y. I., Zoccoli-Rodriguez, V., Taylor, H. E., Endy, T. P., Wilmore, J. R., Winslow, G.10.1101/2020.09.04.20187724 — Posted: 2020-09-05

While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral blood B cell immunophenotype and plasma antibody responses in 40 recovered non-hospitalized COVID-19 subjects that were enrolled as donors in a convalescent plasma treatment study. We observed a significant negative correlation (more cells less symptoms) between the frequency of peripheral blood memory B cells and the duration of symptoms for convalescent subjects . Memory B cell subsets in convalescent subjects were composed of classical CD24+ class-switched memory B cells, but also activated CD24-negative and natural unswitched CD27+ IgD+ IgM+ subsets. Memory B cell frequency was significantly correlated with both IgG1 and IgM responses to the SARS-CoV-2 spike protein receptor binding domain (RBD). IgM+ memory, but not switched memory, directly correlated with virus-specific antibody responses, and remained stable over time. Our findings suggest that the frequency of memory B cells is a critical indicator of disease resolution, and that IgM+ memory B cells play an important role in SARS-CoV-2 immunity.

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MouseDoctor

6 comments

  • Agreed, I follow the science, but do not understand the conclusions.

    I have been on Rituximab for 6 years. I am very interested in immune response and which vaccine, if any, might work for Long-Term Anti-B Cell Patients.

      • So are you suggesting, from the data, that a fairly healthy subset of the population do not necessarily need a vaccine due to T-cell mediated response to initial COVID-19 exposures?

        How about using an attenuated coronavirus that causes a common cold in order to build up memory T-cell mediated immunity that may have cross reactivity to COVID-19? It seems that adolescents don’t develop severe disease due to their exposure to other coronaviruses.

        • There is also definitely some evidence that in some people T-cell responses induced by other coronavirus infections (that cause common colds) may provide some protection against SARS-Cov-2 resulting in some infections being mild. E.g. blood taken from people before COVID-19 was ever heard of shows a T cell response to SARS-CoV-2.

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