The Immunology Unit researches the human host immune response to infectious diseases of high prevalence in Cambodia. Our mission is to provide insight into both the innate and adaptive immune response to various viral infections for novel vaccine and therapeutics design. We aim to improve vaccination strategies for vaccine-preventable diseases and identify novel biomarkers of severity or treatment response.
Dengue viruses (DENV) infect up to 390 million individuals each year, of which 500,000 cases require hospitalization.Since 2012, dengue is the most important vector-borne viral disease of humans and likely more important thanmalaria globally in terms of morbidity and economic impact. The mosquito vectors, Aedes aegypti and Aedesalbopictus both thrive well in populated urbanized areas, contributing to the spread of DENV. DENV is a member ofthe family Flaviviridae, and consists out of 4 related serotypes (DENV-1 to DENV-4). Dengue virus infection resultsin a range of clinical outcomes, from asymptomatic infection, to classic dengue fever (DF), to dengue hemorrhagicfever/dengue shock syndrome (DHF/DSS). Most primary infections are mild and probably provide lifelong protectionagainst the infecting serotype. In contrast, secondary infection with a heterologous DENV serotype can result inmore severe dengue, suggesting that primary DENV infection triggers a host memory immune response thatcan result in either protection or enhancement of subsequent infection. Due to the incomplete understanding ofthe relevant adaptive immune responses leading to protection or enhancement of disease in secondary infectionand the absence of conclusive biomarkers for protection, vaccine development has been severely hampered.Our previous work comparing the immune response in asymptomatic acute infected individuals with hospitalizedpatients revealed profound differences in the adaptive immune response profile associated with a different clinicaloutcome to infection (Simon-Loriere et al, Scie Transl Med, 2017).
ANRS No12358: “MicroRNA (miRNAs) as prediction and/or prognostic markers of IRIS (Immune Reconstitution Inflammatory Syndrome) in TB/HIV co-infected patient (Mirbio)”
MiRNAs are reported as powerful regulators of post-translational gene expression and can act as biomarkers in several infectious diseases. Host miRNAs target certain HIV genes, affecting HIV replication thus thereby
participating in viral control. In HIV elite controllers, a set of expressed miRNA can characterize this clinical phenotype. Several studies reported the characterization of miRNA expression profile in tuberculosis (TB) patients,
but evaluation of miRNA expression in co-infections such as TB/HIV are lacking. Hence, we aim to evaluate by flow cytometry whether a circulating miRNA pattern might be used as potential biomarkers in HIV/TB coinfection and to correlate the miRNA expression profile of 28 selected miRNAs with the clinical evolution and the occurrence of IRIS. Interestingly, we identified two miRNA candidates (miR-150 and miR-145) that could discriminate between
HIV-TB co-infection from HIV, TB mono infection and healthy controls. As a next step, we will analyze exomiR, miRNA in the plasma-secreted exosome. The statistical analysis and manuscript preparation will be done in 2020.
The international health authorities are backing an effort to eliminate canine-mediated rabies in humans by 2030.
This will require improving access to adequate and timely post-exposure rabies prophylaxis. All individuals were referred to the rabies prevention clinic at IP Cambodia and received two-dose intradermal PEP at days 0, 3, 7 and
28. We showed that all individuals demonstrated rabies virus neutralizing antibody titers considered protective (≥ 0.5 IU/ml) at day 28, immediately before the last injection. Protective titers were reached notwithstanding eRIG
use, age, sex, nutrition status or dog infective status (Cantaert T, Borand L et al, Lancet Infect dis 2019). Hence, we provide evidence that rabies PEP can be abridged to a two-dose, three-sessions, one week (D0, D3, D7 regimen.
Based on these results the WHO endorsed changes in its April 2018 guidelines. This “IPC protocol” is the first one week PEP regimen to be recommended and the shortest and most vaccine-sparing rabies PEP protocol endorsed.
Head of unit
Deputy Head of unit