BCG-induced immunity profiles in household contacts of leprosy patients differentiate between protection and disease

Anouk van Hooij; Susan J.F. van den Eeden; Marufa Khatun; Santosh Soren; Kees L.M.C. Franken; Johan Chandra Roy; Khorshed Alam; Abu Sufian Chowdhury; Jan Hendrik Richardus; Annemieke Geluk

doi:10.1016/j.vaccine.2021.10.027

BCG-induced immunity profiles in household contacts of leprosy patients differentiate between protection and disease

Anouk van Hooij, Susan J.F. van den Eeden, Marufa Khatun, Santosh Soren, Kees L.M.C. Franken, Johan Chandra Roy, Khorshed Alam, Abu Sufian Chowdhury, Jan Hendrik Richardus, Annemieke Geluk^*

^*Corresponding author for this work

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Abstract

Leprosy is an infectious disease caused by Mycobacterium leprae leading to irreversible disabilities along with social exclusion. Leprosy is a spectral disease for which the clinical outcome after M. leprae infection is determined by host factors. The spectrum spans from anti-inflammatory T helper-2 (Th2) immunity concomitant with large numbers of bacteria as well as antibodies against M. leprae antigens in multibacillary (MB) leprosy, to paucibacillary (PB) leprosy characterised by strong pro-inflammatory, Th1 as well as Th17 immunity. Despite decades of availability of adequate antibiotic treatment, transmission of M. leprae is unabated. Since individuals with close and frequent contact with untreated leprosy patients are particularly at risk to develop the disease themselves, prophylactic strategies currently focus on household contacts of newly diagnosed patients. It has been shown that BCG (re)vaccination can reduce the risk of leprosy. However, BCG immunoprophylaxis in contacts of leprosy patients has also been reported to induce PB leprosy, indicating that BCG (re)vaccination may tip the balance between protective immunity and overactivation immunity causing skin/nerve tissue damage. In order to identify who is at risk of developing PB leprosy after BCG vaccination, amongst individuals who are chronically exposed to M. leprae, we analyzed innate and adaptive immune markers in whole blood of household contacts of newly diagnosed leprosy patients in Bangladesh, some of which received BCG vaccination. As controls, individuals from the same area without known contact with leprosy patients were similarly assessed. Our data show the added effect of BCG vaccination on immune markers on top of the effect already induced by M. leprae exposure. Moreover, we identified BCG-induced markers that differentiate between protective and disease prone immunity in those contacts.

Original language	English
Pages (from-to)	7230-7237
Number of pages	8
Journal	Vaccine
Volume	39
Issue number	50
DOIs	https://doi.org/10.1016/j.vaccine.2021.10.027
Publication status	Published - 8 Dec 2021

Bibliographical note

Funding Information:
This study was supported by the Leprosy Research Initiative (LRI) together with the Turing Foundation (ILEP#: 703.15.07), an R2STOP Research grant from Effect hope/The Leprosy Mission Canada, the Order of Malta-Grants-for-Leprosy-Research (MALTALEP), the Q.M. Gastmann-Wichers Foundation (to AG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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© 2021

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BCG-induced immunity profiles in household contacts of leprosy patients differentiate between protection and diseaseFinal published version, 1.75 MBLicence: CC BY

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@article{e19ce0c9523d4c318f1a6d641d2e318c,

title = "BCG-induced immunity profiles in household contacts of leprosy patients differentiate between protection and disease",

abstract = "Leprosy is an infectious disease caused by Mycobacterium leprae leading to irreversible disabilities along with social exclusion. Leprosy is a spectral disease for which the clinical outcome after M. leprae infection is determined by host factors. The spectrum spans from anti-inflammatory T helper-2 (Th2) immunity concomitant with large numbers of bacteria as well as antibodies against M. leprae antigens in multibacillary (MB) leprosy, to paucibacillary (PB) leprosy characterised by strong pro-inflammatory, Th1 as well as Th17 immunity. Despite decades of availability of adequate antibiotic treatment, transmission of M. leprae is unabated. Since individuals with close and frequent contact with untreated leprosy patients are particularly at risk to develop the disease themselves, prophylactic strategies currently focus on household contacts of newly diagnosed patients. It has been shown that BCG (re)vaccination can reduce the risk of leprosy. However, BCG immunoprophylaxis in contacts of leprosy patients has also been reported to induce PB leprosy, indicating that BCG (re)vaccination may tip the balance between protective immunity and overactivation immunity causing skin/nerve tissue damage. In order to identify who is at risk of developing PB leprosy after BCG vaccination, amongst individuals who are chronically exposed to M. leprae, we analyzed innate and adaptive immune markers in whole blood of household contacts of newly diagnosed leprosy patients in Bangladesh, some of which received BCG vaccination. As controls, individuals from the same area without known contact with leprosy patients were similarly assessed. Our data show the added effect of BCG vaccination on immune markers on top of the effect already induced by M. leprae exposure. Moreover, we identified BCG-induced markers that differentiate between protective and disease prone immunity in those contacts.",

author = "{van Hooij}, Anouk and {van den Eeden}, {Susan J.F.} and Marufa Khatun and Santosh Soren and Franken, {Kees L.M.C.} and {Chandra Roy}, Johan and Khorshed Alam and Chowdhury, {Abu Sufian} and Richardus, {Jan Hendrik} and Annemieke Geluk",

note = "Funding Information: This study was supported by the Leprosy Research Initiative (LRI) together with the Turing Foundation (ILEP#: 703.15.07), an R2STOP Research grant from Effect hope/The Leprosy Mission Canada, the Order of Malta-Grants-for-Leprosy-Research (MALTALEP), the Q.M. Gastmann-Wichers Foundation (to AG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = dec,

day = "8",

doi = "10.1016/j.vaccine.2021.10.027",

language = "English",

volume = "39",

pages = "7230--7237",

journal = "Vaccine",

issn = "0264-410X",

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T1 - BCG-induced immunity profiles in household contacts of leprosy patients differentiate between protection and disease

AU - van Hooij, Anouk

AU - van den Eeden, Susan J.F.

AU - Khatun, Marufa

AU - Soren, Santosh

AU - Franken, Kees L.M.C.

AU - Chandra Roy, Johan

AU - Alam, Khorshed

AU - Chowdhury, Abu Sufian

AU - Richardus, Jan Hendrik

AU - Geluk, Annemieke

N1 - Funding Information: This study was supported by the Leprosy Research Initiative (LRI) together with the Turing Foundation (ILEP#: 703.15.07), an R2STOP Research grant from Effect hope/The Leprosy Mission Canada, the Order of Malta-Grants-for-Leprosy-Research (MALTALEP), the Q.M. Gastmann-Wichers Foundation (to AG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021

PY - 2021/12/8

Y1 - 2021/12/8

N2 - Leprosy is an infectious disease caused by Mycobacterium leprae leading to irreversible disabilities along with social exclusion. Leprosy is a spectral disease for which the clinical outcome after M. leprae infection is determined by host factors. The spectrum spans from anti-inflammatory T helper-2 (Th2) immunity concomitant with large numbers of bacteria as well as antibodies against M. leprae antigens in multibacillary (MB) leprosy, to paucibacillary (PB) leprosy characterised by strong pro-inflammatory, Th1 as well as Th17 immunity. Despite decades of availability of adequate antibiotic treatment, transmission of M. leprae is unabated. Since individuals with close and frequent contact with untreated leprosy patients are particularly at risk to develop the disease themselves, prophylactic strategies currently focus on household contacts of newly diagnosed patients. It has been shown that BCG (re)vaccination can reduce the risk of leprosy. However, BCG immunoprophylaxis in contacts of leprosy patients has also been reported to induce PB leprosy, indicating that BCG (re)vaccination may tip the balance between protective immunity and overactivation immunity causing skin/nerve tissue damage. In order to identify who is at risk of developing PB leprosy after BCG vaccination, amongst individuals who are chronically exposed to M. leprae, we analyzed innate and adaptive immune markers in whole blood of household contacts of newly diagnosed leprosy patients in Bangladesh, some of which received BCG vaccination. As controls, individuals from the same area without known contact with leprosy patients were similarly assessed. Our data show the added effect of BCG vaccination on immune markers on top of the effect already induced by M. leprae exposure. Moreover, we identified BCG-induced markers that differentiate between protective and disease prone immunity in those contacts.

AB - Leprosy is an infectious disease caused by Mycobacterium leprae leading to irreversible disabilities along with social exclusion. Leprosy is a spectral disease for which the clinical outcome after M. leprae infection is determined by host factors. The spectrum spans from anti-inflammatory T helper-2 (Th2) immunity concomitant with large numbers of bacteria as well as antibodies against M. leprae antigens in multibacillary (MB) leprosy, to paucibacillary (PB) leprosy characterised by strong pro-inflammatory, Th1 as well as Th17 immunity. Despite decades of availability of adequate antibiotic treatment, transmission of M. leprae is unabated. Since individuals with close and frequent contact with untreated leprosy patients are particularly at risk to develop the disease themselves, prophylactic strategies currently focus on household contacts of newly diagnosed patients. It has been shown that BCG (re)vaccination can reduce the risk of leprosy. However, BCG immunoprophylaxis in contacts of leprosy patients has also been reported to induce PB leprosy, indicating that BCG (re)vaccination may tip the balance between protective immunity and overactivation immunity causing skin/nerve tissue damage. In order to identify who is at risk of developing PB leprosy after BCG vaccination, amongst individuals who are chronically exposed to M. leprae, we analyzed innate and adaptive immune markers in whole blood of household contacts of newly diagnosed leprosy patients in Bangladesh, some of which received BCG vaccination. As controls, individuals from the same area without known contact with leprosy patients were similarly assessed. Our data show the added effect of BCG vaccination on immune markers on top of the effect already induced by M. leprae exposure. Moreover, we identified BCG-induced markers that differentiate between protective and disease prone immunity in those contacts.

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BCG-induced immunity profiles in household contacts of leprosy patients differentiate between protection and disease

Abstract

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