Determining the duration of the immune response and understanding the differences depending on whether it is generated by natural SARS-CoV-2 infection or by vaccination will be key to improving existing vaccines. In this sense, the Infectious Diseases group of the Vall d'Hebron Research Institute (VHIR) has led a study that has demonstrated the presence of resident immune cells in the lungs of vaccinated people. These cells, while not able to prevent infection, contribute to the control of the disease as they can kill infected cells. The study, published in Nature Communications, was carried out in collaboration with the Thoracic Surgery and Lung Transplantation Service and the Respiratory Virus Unit of the Microbiology Service of the Vall d'Hebron University Hospital.

A study published in the same journal, Nature Communications, in 2021 by the same team identified the presence of lung-resident memory T lymphocytes in people who had recovered from COVID-19. These immune cells are found in the most superficial layer of the airways and are one of the first lines of defense against possible future SARS-CoV-2 infections. This time, they have also studied the presence of immune cells in the lung in people vaccinated with Pfizer-BioNTech or Moderna (mRNA vaccines). So far, in the case of vaccination, international studies have focused on the response of antibodies and memory cells circulating in the blood, but the response in the lungs is unknown.

Now, the researchers have compared the resident memory T-cell response in lung samples from four groups of people: uninfected and unvaccinated, infected unvaccinated, uninfected and vaccinated with two doses, and uninfected and vaccinated with three doses (the last one was recent). "We observed that the lungs of vaccinated people had specific memory T cells against SARS-CoV-2 after more than 6 months after the second dose of vaccine. However, the response was lower than in patients who had recovered from COVID-19 and their profile less frequently had resident cell characteristics. This would indicate that these cells may be less able to provide long-lasting protection and, above all, to be a first line of defense", explains Dr. Daan K.J. Pieren, a researcher in VHIR's Infectious Diseases group and first author of the paper.

In relation to the administration of the third dose, the work showed an increase in the immune response present in blood and lung, but no differences were seen in the subtypes of cells present in the lung. "The vaccines that have been administered so far generate a response that is distributed in a generalized way throughout our body, but is not directed to the respiratory tract. Instead, the respiratory tract infection that occurs after natural infection with the virus stimulates our immune response to establish itself as a long-lasting resident memory in the affected tissue", says Dr. Meritxell Genescà, principal investigator of the Infectious Diseases group at VHIR, who has led the study. "In any case, even if it is a limited response, it is good news that we found established memory cells in the lung of vaccinated people, because these cells will contribute to reduce the severity of the disease", highlights Dr. Genescà.

To improve the efficacy of future vaccines, the researchers propose administration through other routes than intramuscular, such as intranasal, as this would allow them to reach the affected area directly. In fact, booster vaccines using these routes have already been approved in some countries. They also recommend targeting different proteins of the virus to achieve a more complete and effective response, as currently approved vaccines use a single SARS-CoV-2 protein known as protein S or Spike to stimulate our immune system.

The study was carried out on lung samples from 30 people obtained from biopsies taken for various reasons, such as the presence of a tumor. Despite being a small sample, it provides valuable information due to the difficulty involved in obtaining and analyzing this type of tissue at different times during the pandemic.