An article published in Nature presents evidence of lasting immunity in most people after SARS-CoV-2 infection. It also analyzes the interpretation, often wrong, about the meaning of the fall in antibody levels and of this phenomenon being used as a justification for revaccination. Tiago Marques, an infectious disease specialist, comments on the study and analyzes the situation in Portugal.
In an article published in the journal Nature, the topic of the duration of immunity to SARS-CoV-2 is addressed. The authors describe the main pillars of an antiviral response:
- Immune cells called cytotoxic T cells, which can selectively eliminate infected cells, and neutralizing antibodies;
- Neutralizing antibodies, a type of antibody that prevents a virus from infecting cells, and which is secreted by immune cells called plasma cells.
- The generation of “Helper” T cells, which are specific for the virus and coordinate the immune response.
Now, it is precisely these “Helper” T cells that are involved in the generation of immunological memory. Specifically, they organize the appearance of long-lasting plasma cells, which secrete antiviral antibodies even in the absence of the virus.
Long-term memory
The authors recall that “immunological memory is not an enduring version of the immediate immune response to a particular virus; rather, it is a distinct aspect of the immune system.”
Virus-specific memory B and T cells arise from cells activated in the initial immune response. In the memory phase, B and T cells are kept in a dormant state, but are ready to be activated if they encounter the virus (or a vaccine for it) again.
Long-lasting immunity to SARS-CoV-2
The article describes the dual role of B cells in immunity:
– Production of antibodies that recognize viral proteins, and presentation of parts of these proteins to specific T cells;
– Develop into plasma cells that produce antibodies in large quantities.
These plasma cells “can become memory cells, and secrete antibodies for lasting protection”, and can remain for decades, if not a lifetime, in the bone marrow.
Despite being extremely scarce, as they are specific for each disease-causing agent, an investigation was able to detect memory plasma cells for SARS-CoV-2 in 15 of 19 individuals (7 months after infection).
After 4 months (11 months after SARS-CoV-2 infection), the number of plasma cells remained stable in the subjects analyzed (with one exception). As these cells did not multiply, they can be classified as proper memory cells.
The authors point out that:
“Their numbers matched those of memory plasma cells found in subjects after vaccination against tetanus or diphtheria, and which provide long-term immunity to these diseases.”
Long-term immunity mechanism similar to many viruses
In the mentioned study, it was possible to observe that the concentrations of antibodies against SARS-CoV-2 followed a biphasic pattern (Fig. 1). That is, in the acute immune response during the initial infection, antibody concentrations are high.
Then they decline, as expected, because most plasma cells in an acute immune response are short-lived. After a few months, antibody concentrations stabilized and remained more or less constant, with about 10-20% of the maximum observed concentration.
For the researchers such a fact “is consistent with the expectation that 10 to 20% of plasma cells in an acute immune reaction will become memory plasma cells, and is a clear indication of a shift from short-lived plasma cell antibody production to the production of antibodies by memory plasma cells.”
They conclude that:
“This is not unexpected, given that immune memory for many viruses and vaccines is stable over decades, if not for a lifetime.”
Consequences for the analysis of vaccine efficacy
The authors point out to the error in the evaluation of the vaccine’s efficacy that arises from the expectation that the high concentrations of antibodies, characteristic of acute immune reactions, are maintained in the memory phase.
“It is an old misconception, when advocating frequent revaccinations, that antibody concentrations during the acute immune reaction can be compared with later ones to calculate an imaginary “half-life” of antibody-mediated immunity.”
In conclusion, they highlight that “the evidence so far predicts that infection with SARS-CoV-2 induces long-term immunity in most individuals” and that more data on memory responses to vaccination are awaited.
We asked infectious disease specialist Tiago Marques to comment on the article and to interpret the current situation in Portugal:
“The authors prove that the immune response to SARS-CoV-2 is as expected and does not differ from the response to other viral infections (and even that described in SARS-CoV-1). After an acute infection, and in the absence of viral persistence in the body (examples of herpes, cytomegalovirus, mononucleosis virus…), the blood concentration (titer) of antibodies tends to decrease over time, and immunity is maintained by memory cells. (it would not be physiologically possible to maintain maximum antibody titers for all antigens we come into contact with throughout life).
At the same time there is a maturation of the antibodies, so lower titers ensure the same effectiveness as their affinity increases (many antibodies produced in the initial phase are non-neutralizing and these are eliminated over time in favor of high affinity IgG antibodies in lower title). On the other hand, persistent memory cells have the ability to reactivate the production of antibodies if necessary (anamnestic response).
However, and as in many respiratory viruses in which there are small variations due to virus mutation (antigenic drift), SARS-CoV-2 reinfections are frequent and even expected (the four seasonal coronaviruses that exist are characterized by frequent reinfections even with high antibody titers, their severity being limited by the T cell response).
At the moment there is a high incidence of SARS-CoV-2 infection in Portugal, although there is not the severity seen in the alpha wave, for example. This should not be interpreted in the same way as in other periods of pandemic activity, characterized by high incidence and severity in a naive population (as there were no SARS-CoV-2 reactive T cells to limit severity, the expression of the infection was much more burdensome). At this point, we note that although the number of infections is very high, their severity is much lower than what traditionally occurred, which reflects the existing immunity (vaccination and also natural by exposure to the virus) in the population, and suggests the evolution in parallel. with seasonal coronaviruses.
Probably the SARS-CoV-2 will tend to evolve in more or less time to seasonality, there is currently a high degree of immunity in the general population, so in the absence of high repercussions in intensive care (and therefore, serious disease), the number of infections means very little (however, risks remain for the immunocompromised population – especially with malignant hematological disease and certain types of immunotherapy – who must maintain particular care).”
