I am a senior researcher in the group of Professor Lennart Hammarström at the Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine. I am supervising the Immunotherapy group and my research focus on passive immunization using Lactobacillus expressing antibody fragments against mucosal pathogens.
1987-1990 B.Sc. in Microbiology, Department of Biochemistry, Université Laval, Canada
1990-1992 M.Sc. in Microbiology, Department of Biochemistry, Université Laval, Canada
1992-1997 Ph.D. in Microbiology and Immunology, Faculty of Medecine, Université Laval, Canada
Passive administration of antibodies represents the therapy of choice for mucosal infections, particularly in children and immunocompromised individuals and during the past two decades, oral administration of polyclonal antibodies against selected enteric pathogens has been employed successfully. However, production and purification of these antibodies is costly and therefore, efforts have been made to develop new methods for production of monoclonal antibodies or antibody fragments employing plant, yeast and bacterial systems.
An attractive idea is to use lactobacilli as vectors for in situ delivery of antibody fragments and other therapeutic molecules at mucosal surfaces. Lactobacilli are Gram-positive bacteria with a long history of safe use in food fermentation and preservation. They are also a significant component of the naturally occuring gastrointestinal and vaginal microbiota. The desired genes can be integrated into the bacterial genome, creating food grade, genetically modified lactobacilli. The modified lactobacilli can be freeze-dried or spray dried and subsequently incorporated in capsules or food products. We have previously shown that genetically modified lactobacilli delivering antibody fragments against S. mutans (Krüger et al. 2002), rotavirus (Pant et al. 2006, Alvarez et al. 2015), and C. difficile (Andersen et al. 2015) are protective in animal models. In addition, lactobacilli can be used to deliver a ranged of therapeutic molecules in the gastrointestinal tract such as cytokines, antimicrobial peptides and glucacon-like peptides.
Our current research projects include:
- Generation of antibody fragments against mucosal pathogens
- Delivery of antibody fragments against mucosal pathogens (norovirus, HIV) by lactobacilli
- Lactobacilli delivering cytokines (IL-10, IL-21, IL-22) and CD40L for treatment of inflammatory diseases and IgA deficiency
- Treatment of bacterial vaginosis using a combination of antibiotics and probiotics
Krüger C, Hu Y, Pan Q, Marcotte H, Hultberg A, Delwar D, van Dalen PJ, Pouwels PH, Leer RJ, Kelly CG, van Dollenweerd C, Ma JK, Hammarström L. In situ delivery of passive immunity by lactobacilli producing single-chain antibodies. Nat Biotechnol. 2002 Jul; 20(7):702-6. PMID: 12089555
Pant N, Hultberg A, Zhao Y, Svensson L, Pan-Hammarstrom Q, Johansen K, Pouwels PH, Ruggeri FM, Hermans P, Frenken L, Boren T, Marcotte H, Hammarstrom L. Lactobacilli expressing variable domain of llama heavy-chain antibody fragments (lactobodies) confer protection against rotavirus-induced diarrhea. J Infect Dis. 2006 Dec 1; 194(11):1580-8. PMID: 17083044
Martín MC, Pant N, Ladero V, Günaydin G, Andersen KK, Alvarez B, Martínez N, Alvarez MA, Hammarström L, Marcotte H. Integrative expression system for delivery of antibody fragments by lactobacilli. Appl Environ Microbiol. 2011 Mar; 77(6):2174-9. PMID: 21257814
Pant N, Marcotte H, Hermans P, Bezemer S, Frenken L, Johansen K, Hammarström L. Lactobacilli producing bispecific llama-derived anti-rotavirus proteins in vivo for rotavirus-induced diarrhea. Future Microbiol. 2011 May; 6(5):583-93. PMID: 21585264
Larsson PG, Brandsborg E, Forsum U, Pendharkar S, Andersen KK, Nasic S, Hammarström L, Marcotte H. Extended antimicrobial treatment of bacterial vaginosis combined with human lactobacilli to find the best treatment and minimize the risk of relapses. BMC Infect Dis. 2011 Aug 19; 11:223. PMID: 21854593
Tokuhara D, Álvarez B, Mejima M, Hiroiwa T, Takahashi Y, Kurokawa S, Kuroda M, Oyama M, Kozuka-Hata H, Nochi T, Sagara H, Aladin F, Marcotte H, Frenken LG, Iturriza-Gómara M, Kiyono H, Hammarström L, Yuki Y. Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection. J Clin Invest. 2013 Sep; 123(9):3829-38. PMID: 23925294
Günaydın G, Zhang R, Hammarström L, Marcotte H. Engineered Lactobacillus rhamnosus GG expressing IgG-binding domains of protein G: Capture of hyperimmune bovine colostrum antibodies and protection against diarrhea in a mouse pup rotavirus infection model. Vaccine. 2014 Jan 16; 32(4):470-7. PMID: 24291196
Günaydın G, Alvarez B, Lin Y, Hammarström L, Marcotte H. Co-expression of anti-rotavirus proteins (llama VHH antibody fragments) in Lactobacillus: development and functionality of vectors containing two expression cassettes in tandem. PLoS One. 2014 Apr 29; 9(4):e96409. PMID: 24781086
Pendharkar S, Brandsborg E, Hammarström L, Marcotte H, Larsson PG. Vaginal colonisation by probiotic lactobacilli and clinical outcome in women conventionally treated for bacterial vaginosis and yeast infection. BMC Infect Dis. 2015 Jul 3; 15:255. PMID: 26137971
Álvarez B, Krogh-Andersen K, Tellgren-Roth C, Martínez N, Günaydın G, Lin Y, Martín MC, Álvarez MA, Hammarström L, Marcotte H. An Exopolysaccharide-deficient mutant of Lactobacillus rhamnosus GG efficiently displays a protective llama antibody fragment against rotavirus on its surface. Appl Environ Microbiol. 2015 Sep 1; 81(17):5784-93. PMID: 26092449
Andersen KK, Strokappe NM, Hultberg A, Truusalu K, Smidt I, Mikelsaar RH, Mikelsaar M, Verrips T, Hammarström L, Marcotte H. Neutralization of Clostridium difficile toxin B mediated by engineered lactobacilli producing single domain antibodies. Infect Immun. 2015 Nov 16. PMID: 26573738