A safe and efficient BCG vectored vaccine to prevent the disease caused by the human Respiratory Syncytial Virus

Abstract

The human Respiratory Syncytial Virus (hRSV) causes lower respiratory tract infections including pneumonia and bronchiolitis. Such infections also cause a large number of hospitalizations and affects mainly newborns, young children and the elderly worldwide. Symptoms associated with hRSV infection are due to an exacerbated immune response characterized by low levels of IFN-γ, recruitment of neutrophils and eosinophils to the site of infection and lung damage. Although hRSV is a major health problem, no vaccines are currently available. Different immunization approaches have been developed to achieve a vaccine that activates the immune system, without triggering an unbalanced inflammation. These approaches include live attenuated vaccine, DNA or proteins technologies, and the use of vectors to express proteins of the virus. In this review, we discuss the host immune response to hRSV and the immunological mechanisms underlying an effective and safe BCG vectored vaccine against hRSV.

Keywords: BCG; hRSV immune response; hRSV vaccine.

Figure 1.

Immune response induced by hRSV in absence or presence of the recombinant rBCG-N-hRSV vaccine. hRSV induce an aberrant immune response due to the erratic T cell polarization, producing a high pro-inflammatory and allergic-like response (A). On the other hand, the rBCG-N-hRSV induces an effective immune response that could control the infection through the polarization of CD4⁺ and CD8⁺ T cells and neutralizing antibodies decreasing the recruitment of immune cells such as neutrophils, eosinophils and the mucus secretion (B).

Figure 2.

Proposed mechanism of the rBCG-N-hRSV vaccine that controls the hRSV-infection. Subsequent to the rBCG-N-hRSV infection and the viral infection, the events goes as follows. (1) Immunological synapsis between the APC (Dendritic cells) and T cells. (2) T_H-1 response polarization and secretion of IFN-γ by CD4⁺ and CD8⁺ T cells. (3) Activation of B cells by the T cells. (4) Antibodies secretion by plasma cells with the proper neutralizing isotype. (5) Cytotoxic activity of the CD8⁺ T cell and depletion of infected-cells. (6) A T_H-17 profile induction suggests a possible way of control for the exacerbated T_H-1 response. (7) Possible IL-27 secretion and proliferation of CD4⁺ T cells and induction of IFN-γ secretion. (8) IL-27 secretion could inhibit the T_H-17 response. (9) Relation between the T_H-17⁺ T_reg that might decrease the hRSV-pathology.