Differences in responses to the intracellular macrophage environment between Mycobacterium bovis BCG vaccine strains Moreau and Pasteur

BACKGROUND The Bacille Calmette-Guérin (BCG) vaccine comprises a family of strains with variable protective efficacy against pulmonary tuberculosis (TB) and leprosy, partly due to genetic differences between strains. OBJECTIVES Previous data highlighting differences between the genomes and proteomic profiles of BCG strains Moreau and Pasteur led us to evaluate their behaviour in the macrophage microenvironment, capable of stimulating molecular responses that can impact the protective effect of the vaccine. METHODS Strain infectivity, viability, co-localisation with acidified vesicles, macrophage secretion of IL-1 and MCP-1 and lipid droplet biogenesis were evaluated after infection. FINDINGS We found that BCG Moreau is internalised more efficiently, with significantly better intracellular survival up to 96 h p.i., whereas more BCG Pasteur bacilli were found co-localised in acidified vesicles up to 6 h p.i. IL-1β and MCP-1 secretion and lipid droplet biogenesis by infected macrophages were more prominent in response to BCG Pasteur. MAIN CONCLUSION Overall, our results show that, compared to Pasteur, BCG Moreau has increased fitness and better endurance in the harsh intracellular environment, also regulating anti-microbial responses (lower IL-1b and MCP-1). These findings contribute to the understanding of the physiology of BCG Moreau and Pasteur in response to the intraphagosomal environment in a THP-1 macrophage model.

Bacillus of Calmette and Guérin (BCG) and the risk of leprosy in Ciudad del Este, Paraguay, 2016-2017.

OBJECTIVES: Paraguay has experienced a 35% reduction in the detected incidence of leprosy during the last ten years, as the vaccination coverage against tuberculosis (Bacillus of Calmette and Guérin [BCG] vaccine) reached ≥95% among infants. The objective of this case-control study was to evaluate the protective effect of BCG on the risk of leprosy. METHODS: We used a population-based case-control study of 20 leprosy confirmed cases reported among residents of Ciudad del Este, Paraguay, diagnosed in 2016-2017. Three controls were selected from a random sample of households from the city. We assessed vaccine effectiveness using 1- odds ratio [OR], and confounding for age, gender, education, occupation, and marital status using stratified and exact logistic regression, and explored if there was effect modification calculating the synergy factor (SF) and relative excess risk due to interaction (RERI). RESULTS: After controlling for age, gender, education, occupation and marital status, the OR of BCG scar on the risk of leprosy was 0.10 (95% confidence interval [CI], 0.02 to 0.45), for an estimate of vaccine effectiveness of 89.5% reduced risk of leprosy (95% CI, 55.2 to 98.1). There was evidence of heterogeneity by which the effectiveness of BCG seemed stronger among younger persons (Breslow-Day and Z-test of the SF had a p<0.05), and both the RERI and SF indicated a less then multiplicative and additive interaction of BCG and younger age. CONCLUSIONS: BCG vaccination was associated with a decreased risk of leprosy in the study population, particularly in persons born after 1980.

Spectrum of Inborn errors of immunity in a cohort of 90 patients presenting with complications to BCG vaccination in India.

World Health Organisation recommends the practice of BCG vaccination at birth in countries which have a high incidence of tuberculosis and/or high leprosy burden. The BCG vaccination is considered safe for a competent immune system. However, in children with weakened immune systems cause of which can be primary or secondary, the vaccine may lead to side effects which can be localized or disseminated. In this study, we report a spectrum of inborn errors of immunity (IEI) commonly referred to as primary immunodeficiency disorders (PIDs) diagnosed in a large cohort of patients presenting with complications to BCG vaccination from India. Retrospective data analysis of patients referred to ICMR- National Institute of Immunohematology (ICMR-NIIH) for IEI workup between 2007 and 2019 was done. IEI was identified in n = 52/90 (57.7%) patients presenting with BCG complications. Of these, n = 13(14.4%) patients were diagnosed with severe combined immune deficiency, n = 15(16.7%) with chronic granulomatous disease, n = 19(21.1%) with Inborn errors of IFN-γ immunity, n = 4(4.4%) with Combined immunodeficiency and n = 1(1.1%) with Leucocyte Adhesion Deficiency type1. Majority of cases with BCGosis (88%) had an underlying IEI. This study strongly highlights the need for evaluation of patients with BCG complications for underlying IEI. While disseminated BCGosis strongly predicts underlying IEI, even localized persistent adenitis may be a warning sign of underlying IEI. It is also strongly recommended to record a family history of previous sibling death prior to administration of this live vaccine and deferring live vaccine till the diagnosis of IEI is ruled out in cases with a positive family history.

Bacillus Calmette-Guérin (BCG) vaccine generates immunoregulatory cells in the cervical lymph nodes in guinea pigs injected intra dermally.

This work demonstrates the presence of immune regulatory cells in the cervical lymph nodes draining Bacillus Calmette-Guérin (BCG) vaccinated site on the dorsum of the ear in guinea pigs. It is shown that whole cervical lymph node cells did not proliferate in vitro in the presence of soluble mycobacterial antigens (PPD or leprosin) despite being responsive to whole mycobacteria. Besides, T cells from these lymph nodes separated as a non-adherent fraction on a nylon wool column, proliferated to PPD in the presence of autologous antigen presenting cells. Interestingly, addition of as low as 20% nylon wool adherent cells to these, sharply decreased the proliferation by 83%. Looking into what cells in the adherent fraction suppressed the proliferation, it was found that neither the T cell nor the macrophage enriched cell fractions of this population individually showed suppressive effect, indicating that their co-presence was necessary for the suppression. Since BCG induced granulomas resolve much faster than granulomas induced by other mycobacteria such as Mycobacterium leprae the present experimental findings add to the existing evidence that intradermal BCG vaccination influences subsequent immune responses in the host and may further stress upon its beneficial role seen in Covid-19 patients.

BCG vaccination: Effects on the patterns of pediatric leprosy.

INTRODUCTION: Leprosy in pediatric population continues to remain as one of the major public health problems in India. BCG vaccination has been implicated in producing some protection against leprosy. OBJECTIVES: The present study intended to find out the patterns of leprosy in the pediatric age group (<12 years) and to determine the proportion of paucibacillary (PB) and multibacillary (MB) leprosy cases among the BCG-vaccinated and nonvaccinated groups. METHODOLOGY: It is a cross-sectional study among patients with leprosy up to the age of 12 years attending a tertiary care hospital in Eastern India by comprehensive history taking and through clinical examination. The history of BCG vaccination was enquired and the BCG scar was looked for to determine the BCG-vaccinated and nonvaccinated group. After collecting the data in a predesigned case sheet, the data were analyzed. RESULT: Of the 137 patients included in this study, 71.53% belonged to the 11-12 years age, 27.74% the 5-10 years age, and 1 patient the <5 year age group. The sex ratio was 1:1.63. PB leprosy was more common than MB leprosy. Smear positivity, deformity, and reaction were not very frequent. Among the vaccinated patients, the ratio of PB and MB leprosy was 5.3:1, while in the nonvaccinated group the ratio was 1.2:1. Data analysis showed that the proportion of MB leprosy was statistically significant in the nonvaccinated group than in the vaccinated group (p = 0.0352). CONCLUSION: Our study pointed that BCG vaccination might have a role in enhancing the cell-mediated immunity (CMI).

Importance of epidemiological surveillance of leprosy: analysis of the occurrence of leprosy in intra-domiciliary contacts in a capital in the Brazilian northeast region

Abstract INTRODUCTION Intra-domiciliary contacts are a group with the highest risk of developing leprosy. METHODS A cross-sectional study of intra-domiciliary contacts of new leprosy cases was conducted. A descriptive analysis of the variables was performed. RESULTS Among 190 contacts, 63% were invited to visit the health unit, and 54.2% received the BCG vaccine. The prevalence of leprosy among the contacts was 4.7%. CONCLUSIONS The occurrence of leprosy among the contacts was high and similar to that found previously. There were failures in surveillance actions carried out by health units. Never-before treated cases were found.

Effects of BCG Vaccination on Evolution of Leprosy.

BACKGROUND: BCG vaccine is considered to have immunoprophylactic potential in leprosy. However controversy exists about the extent of prophylaxis it provides. In view of this, a study was undertaken to see the evolution of disease in established cases of leprosy who were already vaccinated with BCG and to compare it with the cases of leprosy who were not vaccinated with BCG. METHODS: 114 newly diagnosed cases of leprosy were studied. Patients were divided into two groups-BCG vaccinated and non-vaccinated. Clinical diagnosis of leprosy was confirmed by bacteriological and histopathological studies in each case. All patients were given standard anti leprosy treatment and were evaluated monthly for a minimum period of one year. RESULTS: All the cases were males in the age group of 20 to 50 years. 25.4% of cases had received BCG vaccine and 74.6% were not vaccinated for the same. No significant difference was observed in the incidence of different types of leprosy in vaccinated and non-vaccinated groups. 25.9% cases in non-vaccinated group developed lepra reaction as compared to 13.8% in vaccinated group. The incidence of deformities and disabilities in vaccinated group was only 10.3% as against 18.8% in non-vaccinated group. The rate of bacillary clearance appeared faster in vaccinated group. CONCLUSIONS: Although there is no significant difference in the pattern of different types of leprosy in BCG vaccinated and non-vaccinated cases, there is reduction in the incidence of reactions as well as deformities and disabilities in BCG vaccinated cases as compared to non-vaccinated cases.