Worldwide, human respiratory syncytial virus (RSV) is the most common etiological agent for acute lower respiratory tract infections (ALRI). RSV-ALRI is the major cause of hospital admissions in young children, and it can cause in-hospital deaths in children younger than six months old. Therefore, RSV remains one of the pathogens deemed most important for the generation of a vaccine. On the other hand, the effectiveness of a vaccine depends on the development of immunological memory against the pathogenic agent of interest. This memory is achieved by long-lived memory T cells, based on the establishment of an effective immune response to viral infections when subsequent exposures to the pathogen take place. Memory T cells can be classified into three subsets according to their expression of lymphoid homing receptors: central memory cells (T_CM), effector memory cells (T_EM) and resident memory T cells (T_RM). The latter subset consists of cells that are permanently found in non-lymphoid tissues and are capable of recognizing antigens and mounting an effective immune response at those sites. T_RM cells activate both innate and adaptive immune responses, thus establishing a robust and rapid response characterized by the production of large amounts of effector molecules. T_RM cells can also recognize antigenically unrelated pathogens and trigger an innate-like alarm with the recruitment of other immune cells. It is noteworthy that this rapid and effective immune response induced by T_RM cells make these cells an interesting aim in the design of vaccination strategies in order to establish T_RM cell populations to prevent respiratory infectious diseases. Here, we discuss the biogenesis of T_RM cells, their contribution to the resolution of respiratory viral infections and the induction of T_RM cells, which should be considered for the rational design of new vaccines against RSV.

Background:Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a live attenuated vaccine mainly administered to newborns and used for over 100 years to prevent the disease caused by Mycobacterium tuberculosis (M. tb). This vaccine can induce immune response polarization towards a Th1 profile, which is desired for counteracting M. tb, other mycobacteria, and unrelated intracellular pathogens. The vaccine BCG has been used as a vector to express recombinant proteins and has been shown to protect against several diseases, particularly respiratory viruses. Methods: BCG was used to develop recombinant vaccines expressing either the Nucleoprotein from SARS-CoV-2 or Andes orthohantavirus. Mice were immunized with these vaccines with the aim of evaluating the safety and immunogenicity parameters. Results: Immunization with two doses of 1 × 10⁸ CFU or one dose of 1 × 10⁵ CFU of these BCGs was safe in mice. A statistically significant cellular immune response was induced by both formulations, characterized as the activation of CD4⁺ and CD8⁺ T cells. Stimulation with unrelated antigens resulted in increased expression of activation markers by T cells and secretion of IL-2 and IFN-γ, while increased secretion of IL-6 was found for both recombinant vaccines; all of these parameters related to a trained immunity profile. The humoral immune response elicited by both vaccines was modest, but further exposure to antigens could increase this response. Conclusions: The BCG vaccine is a promising platform for developing vaccines against different pathogens, inducing a marked antigen-specific immune response.