AGI – At the beginning of the vaccination campaign against Covid-19, a group of doctors and researchers from the Irccs Foundation Istituto Neurologico “Carlo Besta” (Fincb), from the “Mario Negri” Pharmacological Research Institute – Irccs, from the Hospital Senese and the Irccs Casa Sollievo della Sofferenza Foundation, led by the Institute of Biomedical Technologies of the National Research Council of Segrate (Cnr-Itb), has joined forces to study the genetic basis of interindividual differences in the antibody response to anti-vaccination Covid-19 with the BNT162b2 vaccine (Pfizer-Biontech).
The study showed how some subjects with certain genetic variants in the genes of the major histocompatibility complex (property of the cells of a tissue to be recognized as their own by the organism and therefore not eliminated by the immune system) involved in the main defense mechanisms of our immune system produced different quantities of antibodies directed against the Sars-CoV-2 coronavirus antigen. The study is available in open access on ‘Communications Medicine’.
The team conducted a genome-wide genetic association study, evaluating the correlation between millions of genetic variants and antibody levels in the serum of subjects vaccinated against Covid-19, 30 days after vaccination. In fact, since the beginning of the vaccination campaign, a substantial difference had been observed in the quantities of antibodies produced by vaccinated subjects. Geneticists and immunologists immediately wondered what caused this difference.
– Pfizer vaccine vials
“As with most drugs, so also with vaccines each individual can respond in a more or less effective way and this is due, at least in part, to the individual genetic constitution”, explains Francesca Colombo, researcher at the Cnr-Itb, who led the study. “Our study involved 1,351 subjects (healthcare workers vaccinated in the first months of 2021, in the three hospital centers involved in the study), from whom a blood sample was taken for DNA extraction and a serum sample for antibody measurement anti-Sars-CoV-2 after one month after administration of the second dose of the Pfizer-Biontech vaccine”, he adds.
“With the statistical analyzes carried out we discovered that a particular region of the genome, on chromosome 6, was significantly associated with antibody levels”, adds Martina Esposito, first author of the study and research fellow at the Cnr-Itb. “In this specific genomic region there are genes that code for molecules present on the cell surface, involved in immune response mechanisms. These genes – he continues – are very variable (they are the same ones that are evaluated when looking for compatibility between donors of bone marrow, for example) and there are different combinations. Our study highlighted that some combinations were associated with higher antibody levels, while others with lower levels, thus explaining from a genetic point of view the differences in response to vaccination observed between. different individuals”.
Massimiliano Copetti, head of Biostatistics at the Irccs Casa Sollievo della Sofferenza Foundation, explains: “The mathematical models used and the statistical analyzes carried out to arrive at these results are very complex because the interaction between the genes and the genes themselves with the vaccine is complex. The expertise gained in genetic studies over many years of research conducted at Casa Sollievo della Sofferenza has allowed us to manage this complexity in the data, contributing to achieving these important results.”
– Pfizer vaccine vials
Adds Massimo Carella, geneticist biologist and deputy scientific director of the Irccs Casa Sollievo della Sofferenza Foundation: “The identification of specific Hla alleles that confer a predisposition to a high or low production of antibodies after the administration of the anti-Covid vaccine can help us now allow us to differentiate and personalize the vaccination campaign, providing each individual with the most suitable vaccine, i.e. the one that will allow him to produce as many antibodies as possible. This approach can also be extended to other vaccines designed against other diseases, with a view to vaccination of precision supported by vaccinegenomics”. Colombo underlines: “The results of our study partially confirm those already reported by an English group that conducted research similar to ours but on subjects who were administered the vaccine produced by AstraZeneca, and this is very important in genetic studies of of this type, in which genetic differences between different populations can make it difficult to identify the variants truly responsible for the observed biological phenomenon”.
Raffaella Brugnoni, health researcher at the Department of Research and Clinical Development of the Irccs Istituto Neurologico Carlo Besta Foundation concludes: “The strength of this research project lies in the active collaboration between the various partners and in its multi-centre approach, to which we contributed through collection of biological material and serological data fundamental for this study. This is an example of how different scientific communities can collaborate for the advancement of research and common well-being”.
The collaboration of multiple centers at a national level has allowed the enrollment of a good number of subjects and the collection of the related biological material, a fundamental aspect for genetic studies such as this, which by definition require numerous case series in order to obtain robust results. Also for this reason, the researchers already plan to share the data produced with other groups, at an international level, to obtain information regarding the genetics of the response to the anti-Covid-19 vaccines, which may be valid for individuals not only of European origin , but also of other populations of the world.
The study also opens new avenues towards that precision medicine which is increasingly being talked about because, even in the field of vaccines, knowledge of the genetic basis of a more or less effective response could allow a more targeted vaccination campaign, especially for more fragile subjects. The research was funded by the Italian Buddhist Institute Soka Gakkai.
