A study in eBioMedicine, conducted by the University of Verona with the participation of SoLongevity Research, reveals important new information on the serological response to vaccines
What you will find in this article
- The serological response to the virus or vaccine shows great variability at the individual level
- The presence of type M immunoglobulins after vaccination is associated with a higher antibody level and a greater ability to neutralize the virus
- The response to vaccination may depend on pre-existing immunity developed against other coronaviruses
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More than two years after the pandemic began, the mechanisms by which our immune system responds to SARS-CoV-2 infection and to vaccines are still not clear. The reasons for the high variability of this response are not yet understood, and many questions remain open. For example: are there factors associated with greater protection from the disease? Do past infections with other coronaviruses, such as those of the common cold, play a role? And is it possible to identify a marker predictive of the individual response to vaccination?
Several studies are trying to shed light on precisely these aspects: the latest one, to which eBioMedicine (a journal of the Lancet group) dedicated its cover, was conducted by the team of Donato Zipeto at the University of Verona, in collaboration with SoLongevity Research. The results indicate an important role, so far largely uninvestigated, for a class of antibodies, immunoglobulins M (IgM), which is a candidate to be a valid marker of an efficient response to vaccination. And that is not all: they suggest that past encounters with other coronaviruses may provide protection against COVID. But let us take things in order.
IgM and IgG antibodies: an unexpected discovery
Immunoglobulins (Ig) are produced by B lymphocytesLymphocytes are the cells that make up the effective portion of the adaptive immune system; they are able to generate and modify antibodies that will recognize antigens in the future. They are present in primary lymphoid organs, secondary lymphoid organs, peripheral blood and lymph (where they are currently named)., and there are 5 “types”: among these, IgM and IgG are the main antibodies that defend us from infections. IgM are antibodies generally associated with the first phase of an infection: they appear first after exposure to a virus or an antigen, represent a non-specific response and last for a limited time; IgG appear in a second phase, are highly specific and are associated with long-term immune memory. Currently, IgG are mainly used to assess the response to a vaccine.
The starting point of the new study was precisely the little attention shown so far to IgM: what role could they play? “To understand this, we enrolled more than 1,800 healthcare workers vaccinated against COVID-19 with an mRNA vaccine (BioNTech-Pfizer): 1,500 with no history of infection and 300 with a previous infection,” explains Alberto Beretta, President and Scientific Director of SoLongevity. “We then analyzed the nature of their antibody response before vaccination, at the time of the second dose and three weeks later, monitoring and quantifying the presence of both IgM and IgG against the SARS-CoV-2 spike protein (and, for IgG, also against another viral protein, the nucleocapsid protein, or N protein, editor’s note). What emerged was rather unexpected.”
Normally, in fact, when a person who has never encountered the virus targeted by a vaccination is vaccinated, IgM are expected to appear first, but this occurred in only just over a third of the sample (38%). As for the others, half showed only IgG (without IgM) and the other half – even more strangely – developed IgM even after IgG had appeared. Three different pictures therefore emerge.
The meaning of IgM
“We also observed,” Beretta continues, “that the presence of IgM together with IgG is associated with higher levels of total IgG. And that is not all: when IgM are present, the ability of vaccinated people’s sera to neutralize the virus is greater. Finally, we also noticed another anomalous behavior of IgM: in some cases, in vaccinated people with a history of infection, they seem to persist for quite a long time. In short, those who develop IgM after vaccination seem to have the highest probability of developing IgG that neutralize the virus and of being protected for a longer period.”
Credits: Dr. Alessandra Ruggero, University of Verona
“Those who develop IgM after vaccination seem to have the highest probability of developing IgG that neutralize the virus and of being protected for a longer period”
Encounters with other coronaviruses and pre-existing immunity
The results also suggest that the immune response to the coronavirus is influenced by pre-existing immunity. The hypothesis, in fact, is that where only IgG and not IgM production is observed, this is due to the presence of cross-immunity to other coronaviruses, such as those of the common cold. As if, essentially, the response to the vaccine also exploited a pre-existing immune response. “It is not yet clear whether this may translate into increased or reduced vaccine efficiency, but we think it is more likely to contribute in protective terms,” Beretta stresses: “A study recently published in the journal Nature Immunology provides additional evidence for the hypothesis of a protective role of the cross-reactive response stimulated by other coronaviruses. The picture that is emerging is one of a separation between the mechanisms that protect us from infection and those that protect us from disease. The latter seem to be strongly influenced by cross-reactive responses. This complex scenario could account for the great individual variability and leads us to suppose that the new coronavirus probably encountered a population that was already partly immune. Which means it could have been even more devastating.”
These studies can help optimize vaccination strategies for people who have already been infected or for those who do not respond to vaccination by producing IgM. And, overall, help clarify what an effective, protective immune response against infection and against disease is made of.
