Interruption of persistent exposure to leprosy combined or not with recent BCG vaccination enhances the response to Mycobacterium leprae specific antigens

Abstract

Household contacts of multibacillary leprosy patients (HCMB) constitute the group of individuals at the highest risk of developing leprosy. Early diagnosis and treatment of their index cases combined with Bacille Calmette-Guerin (BCG) immunization remain important strategies adopted in Brazil to prevent HCMB from evolving into active disease. In the present study, we assessed the impact of these measures on the immune response to Mycobacterium leprae in HCMB. Peripheral blood mononuclear cells (PBMC) from HCMB (n = 16) were obtained at the beginning of leprosy index case treatment (T0). At this time point, contacts were vaccinated (n = 13) or not (n = 3) in accordance with their infancy history of BCG vaccination and PBMCs were recollected at least 6 months later (T1). As expected, a significant increase in memory CD4 and CD8 T cell frequencies responsive to M. leprae whole-cell sonicate was observed in most contacts. Of note, higher frequencies of CD4+ T cells that recognize M. leprae specific epitopes were also detected. Moreover, increased production of the inflammatory mediators IL1-β, IL-6, IL-17, TNF, IFN-γ, MIP1-β, and MCP-1 was found at T1. Interestingly, the increment in these parameters was observed even in those contacts that were not BCG vaccinated at T0. This result reinforces the hypothesis that the continuous exposure of HCMB to live M. leprae down regulates the specific cellular immune response against the pathogen. Moreover, our data suggest that BCG vaccination of HCMB induces activation of T cell clones, likely through “trained immunity”, that recognize M. leprae specific antigens not shared with BCG as an additional protective mechanism besides the expected boost in cell-mediated immunity by BCG homologues of M. leprae antigens.

Leprosy among schoolchildren in the Amazon region: A cross-sectional study of active search and possible source of infection by contact tracing

“…Besides reducing clinical leprosy among vaccinees, mainly of the MB type, recent data suggested that BCG vaccination of household contacts of MB leprosy patients may induce activation of T cell clones that recognize M . leprae specific antigens not shared with BCG [ 39 ]. The majority (92.5%) of schoolchildren diagnosed with leprosy in this study had one positive BCG scar and the PB form of the disease (80.0%).…”

BCG Vaccination Status, Age, and Gender as Risk Factors for Leprosy in Endemic Areas in the Brazilian Amazon

“…Although not recommended by the World Health Organization (WHO), the application of this vaccination specifically for leprosy prophylaxis is recognized by the WHO for its significant contribution to the decline in the incidence of the disease [ 7 , 24 ]. The BCG vaccine induces the activation of T-cell clones that recognize specific M. leprae epitopes, providing a protective effect against disease progression, including leading to negative PGL-I serological tests that were previously positive [ 6 , 25 ].…”

“…Contacts without a BCG scar or with just one are vaccinated, and with two scars they are not vaccinated. Currently there are still doubts as to whether BCG protects from leprosy [ 5 , 6 , 7 ].…”

Age, gender and BCG vaccination status as risk factors for Leprosy in endemic areas of northern Brazil.

“…Although not recommended by the World Health Organization (WHO), the application of this vaccination speci cally for leprosy prophylaxis is recognized by the WHO for its signi cant contribution to the decline in the incidence of the disease (5,18). The BCG vaccine induces the activation of T-cell clones that recognize speci c M. leprae epitopes, providing a protective effect against disease progression, including leading to negative PGL-I serological tests that were previously positive (4,19).…”

“…Contacts without a BCG scar or with just one are vaccinated, and with two scars they are not vaccinated. And it is currently established that BCG provides some protection against leprosy (3)(4)(5).…”