CV Science

Jean-Claude Sirard PhD Microbiology

Course and current status

Current position

• Team leader in the Centre for infection and Immunity of Lille at the Institut Pasteur de Lille

Education

• 2020        University degree in Health Entrepreneurship (Univ Lille)
• 1997        Diploma of General Immunology (Institut Pasteur, Paris)
• 1995        PhD in Microbiology (Institut Pasteur, Paris - Univ Paris)

Positions

• 2010                    DR2 INSERM (Research Director)
• 2004                    CR1 INSERM (Senior Scientist)
• 2003-2006           Avenir team leader at the Institut Pasteur de Lille
• 1998-2003           Post-doctoral fellow at ISREC, Switzerland. Director : Pr. Kraehenbuhl

Main grants 

• 2006-2009   FP6 STREP-INCO « Novel Therapeutic and Prophylactic Strategies to Control Mucosal Infections by South American Bacterial Strains, SavinMucoPath
• 2009-2011   Maturation funds from Inserm-Transfert ”MucoFlag: Development of recombinant flagellins as mucosal functional molecules to control respiratory infections”
• 2011-2012   FP7 support from Transvac Infrastructure on ”Transcriptional analysis of flagellin-mediated adjuvant activity” and "From mice to appropriate model of human intradermal immunization: efficacy and signature of the TLR5 agonist flagellin in Sus scrofa pigs"
• 2016-2018   JPIAMR “Repurposing disused antibiotics with immune modulators as antimicrobial strategy for respiratory tract infections”
• 2017-2020   ANR "Targeting lung epithelial cells or type 3 innate lymphoid cells for the treatment of respiratory infections Klebsiella pneumoniae"
• 2020-2026   EU H2020 project FAIR "Flagellin aerosol therapy as an immunomodulatory adjunct to the antibiotic treatment of drug-resistant bacterial pneumonia"
• 2023-2028   EU Horizon Europe project NOSEVAC "Innovative nasal vaccines to prevent pathogen colonization and infection in the upper respiratory tract"

Significant publications 

1. Matarazzo L, Costa C, Porte R, Saliou JM, Figeac M, Delahaye F, Bonnefond A, Kloeckner B, Silvin A, Ginhoux F, Faveeuw C, Baldry M, Carnoy C, Sirard JC. 2024. Neutrophil subsets enhance the efficacy of host-directed therapy in pneumococcal pneumonia. Mucosal Immunol
2. Liu X, Van Maele L, Matarazzo L, Soulard D, Alves Duarte da Silva V, de Bakker V, Denereaz J, Bock FP, Taschner M, Ou J, Gruber S, Nizet V, Sirard JC, Veening JW. 2024. A conserved antigen induces respiratory Th17-mediated broad serotype protection against pneumococcal superinfection. Cell Host Microbe 32: 304-14 e8
3. Costa C, Sirard JC, Gibson PS, Veening JW, Gjini E, Baldry M. 2024. Triggering Toll-Like Receptor 5 signaling during pneumococcal superinfection prevents the selection of antibiotic resistance. J Infect Dis 
4. Baldry M, Costa C, Zeroual Y, Cayet D, Pardessus J, Soulard D, Wallet F, Beury D, Hot D, MacLoughlin R, Heuze-Vourc'h N, Sirard JC, Carnoy C. 2024. Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia. Antimicrob Agents Chemother 68: e0086624
5. Casilag F, Matarazzo L, Franck S, Figeac M, Michelet R, Kloft C, Carnoy C, Sirard JC. 2021. The Biosynthetic Monophosphoryl Lipid A Enhances the Therapeutic Outcome of Antibiotic Therapy in Pneumococcal Pneumonia. ACS Infect Dis 7: 2164-75
6. Vijayan A, Van Maele L, Fougeron D, Cayet D, Sirard JC. 2020. The GM-CSF Released by Airway Epithelial Cells Orchestrates the Mucosal Adjuvant Activity of Flagellin. J Immunol 205: 2873-82
7. Porte R, Fougeron D, Munoz-Wolf N, Tabareau J, Georgel AF, Wallet F, Paget C, Trottein F, Chabalgoity JA, Carnoy C, Sirard JC. 2015. A Toll-Like Receptor 5 Agonist Improves the Efficacy of Antibiotics in Treatment of Primary and Influenza Virus-Associated Pneumococcal Mouse Infections. Antimicrob Agents Chemother 59: 6064-72
8. Fougeron D, Van Maele L, Songhet P, Cayet D, Hot D, Van Rooijen N, Mollenkopf HJ, Hardt WD, Benecke AG, Sirard JC. 2015. Indirect Toll-like receptor 5-mediated activation of conventional dendritic cells promotes the mucosal adjuvant activity of flagellin in the respiratory tract. Vaccine 33: 3331-41
9. Van Maele L, Fougeron D, Janot L, Didierlaurent A, Cayet D, Tabareau J, Rumbo M, Corvo-Chamaillard S, Boulenouar S, Jeffs S, Vande Walle L, Lamkanfi M, Lemoine Y, Erard F, Hot D, Hussell T, Ryffel B, Benecke AG, Sirard JC. 2014. Airway structural cells regulate TLR5-mediated mucosal adjuvant activity. Mucosal Immunol 7: 489-500
10. Van Maele L, Carnoy C, Cayet D, Ivanov S, Porte R, Deruy E, Chabalgoity JA, Renauld JC, Eberl G, Benecke AG, Trottein F, Faveeuw C, Sirard JC. 2014. Activation of Type 3 innate lymphoid cells and interleukin 22 secretion in the lungs during Streptococcus pneumoniae infection. J Infect Dis 210: 493-503
11. Van Maele L, Carnoy C, Cayet D, Songhet P, Dumoutier L, Ferrero I, Janot L, Erard F, Bertout J, Leger H, Sebbane F, Benecke A, Renauld JC, Hardt WD, Ryffel B, Sirard JC. 2010. TLR5 signaling stimulates the innate production of IL-17 and IL-22 by CD3(neg)CD127+ immune cells in spleen and mucosa. J Immunol 185: 1177-85
12. Munoz N, Van Maele L, Marques JM, Rial A, Sirard JC, Chabalgoity JA. 2010. Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection. Infect Immun 78: 4226-33
13. Nempont C, Cayet D, Rumbo M, Bompard C, Villeret V, Sirard JC. 2008. Deletion of flagellin's hypervariable region abrogates antibody-mediated neutralization and systemic activation of TLR5-dependent immunity. J Immunol 181: 2036-43
    
    

Patents

1. Novel immunoadjuvant flagellin-based compounds and use thereof. WO2009156405
2. Methods and pharmaceutical compositions for the treatment of respiratory tract infections. WO2011161491
3. Methods and pharmaceutical compositions for the treatment of bacterial infections. WO2015011254
4. Methods and pharmaceutical compositions for the treatment of bacterial superinfections post-influenza. WO2016102536
5. Aerosol composition for pulmonary delivery of flagellin.  WO2023275292 - PCT/EP2022/068149
6. Novel pneumococcal polypeptide antigens. WO2023006825 - PCT/EP2022/0710
   
   
   

Scientific summary

Unraveling immune responses to bacterial pneumonia: pathways to innovative immunointerventions

Respiratory tract infections in general and pneumonia in particular currently represent the third leading cause of death worldwide. Bacterial pneumonia (either community- or hospital-acquired) is a leading cause of morbidity, quality-adjusted life year loss, and mortality in children, adults, and the elderly. Although antibiotics have transformed the management and treatment, their effectiveness is declining - because of antimicrobial resistance (AMR). The WHO estimates that bacterial infections due to AMR will outcompete any cause of death by 2050, meaning that it is crucial to develop new strategies to improve antibacterial treatment. The WHO defined a priority list of bacteria for which new antibacterial therapies are urgently needed; it includes the major pneumonia-causing pathogens Klebsiella pneumoniae, and Streptococcus pneumoniae, that are studied in the laboratory.

My team aims at developing new adjuvants to stimulate respiratory immunity in prophylaxis and therapeutic settings. Targeting the innate immune system is an underexploited area of drug discovery for infectious diseases. Toll-like receptors (TLR) play a key role in sensing microorganisms and in regulating host innate immune defenses and adaptive immunity against pathogenic bacteria. Deciphering the mode of action of TLR agonist following respiratory administration is a major issue to adjunct antibiotics and vaccines, and thus tackle pneumonia. Flagellin, a protein component of many motile bacterial pathogens, signals through TLR5 is a promising biologic to circumvent pneumonia. The laboratory is currently in the process to launch a Phase I clinical trial to assess aerosol delivery of flagellin as a respiratory adjuvant (fair-flagellin.eu), a significant step towards clinical applications. Furthermore, my team is developing innovative nasal vaccines to prevent the nasal colonization by S. pneumoniae within the EU project Nosevac (nosevac-project.eu).