Parenteral Vaccination With a Tuberculosis Subunit Vaccine in Presence of Retinoic Acid Provides Early but Transient Protection to M. Tuberculosis Infection

Abstract

Most microbes invading through mucosal surfaces cause disease and therefore strategies to induce mucosal immune responses are strongly needed. Vitamin A metabolites, such as retinoic acid (RA), play crucial roles in programming T and B cells to home to mucosal compartments, therefore we evaluated the capacity of RA to elicit mucosal immune responses against tuberculosis (TB) after parenteral vaccination. We found that mice immunized through subcutaneous injections with the TB subunit vaccine (CAF01+H56) in presence of RA show enhanced mucosal H56-specific IgA responses and enhanced Ag-specific CD4 + T lymphocytes homing to the lung as compared with control mice. Immunization with CAF01+H56 in presence of RA resulted in lower bacterial loads in the lungs of mice 14 days after challenge with virulent Mycobacterium tuberculosis (Mtb) as compared to mice immunized in the absence of RA or vaccinated with BCG. Higher amounts of IFNγ and IL-17 pro-inflammatory cytokines were found in lung homogenates of mice immunized with CAF01+H56 and RA 24 h after Mtb infection. However, 6 weeks after infection the protection was comparable in vaccinated mice with or without RA even though treatment with RA during immunization is able to better contain the inflammatory response by the host. Furthermore, at later stage of the infection a higher percentage of Mtb specific CD4 + PD1 + T lymphocytes were found in the lungs of mice immunized with CAF01+H56 and RA. These data show that an enhanced mucosal immune response is generated during parenteral vaccination in presence of RA. Furthermore, RA treatment contained the bacterial growth at an early stage of the infection and limited the inflammatory response in the lung at later time points.

In silico analysis of epitope-based vaccine candidate against tuberculosis using reverse vaccinology

“…Tuberculosis (TB) is a life threating disease and the TB vaccines used globally, the BCG vaccine, offers limited protection against TB for children, and adults, which accounts for most of the TB cases worldwide 66 . Therefore, new candidate vaccine against TB are extremely needed and some of them are under evaluation in clinical trials.…”

Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis

“…In a murine model, ATRA administration in combination with HRZ has demonstrated its potential to shorten TB treatment and decrease relapse events [ 33 ], as well as decreasing the frequency of MDSCs in the lungs of mice with TB, significantly reducing bacterial loads, decreasing granuloma size and ameliorating pathology [ 19 ]. ATRA treatment also enhanced mucosal immune responses following parenteral vaccination with a TB subunit vaccine, by programming T and B cells to home to mucosal compartments [ 34 ].…”

Therapeutic Vaccination with Cationic Liposomes Formulated with Dioctadecyldimethylammonium and Trehalose Dibehenate (CAF01) and Peptide P10 Is Protective in Mice Infected with Paracoccidioides brasiliensis

“…The Cationic Adjuvant Formulation (CAF01 comprised by DDA/TDB) was developed as a safe adjuvant for humans and animals and its mechanism of action is through the triggering of Th 1 responses [31]. CAF adjuvant has been tested in either human or animals infections with Chikungunya vírus [47], Influenza [48], Chlamydia trachomatis [49], Mycobacterium tuberculosis [50,51], Plasmodium falciparum [52], and Streptococcus pyogenes [53].…”