Craig Heal
Fri, Jun-28-02, 20:56
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nbt/journal/-
v20/n7/abs/nbt0 702-702.html&filetype=
July 2002 Volume 20 Number 7 pp 702 - 706
In situ delivery of passive immunity by lactobacilli producing
single-chain antibodies
Carina Krüger1, Yanzhong Hu1, Qiang Pan1, Harold Marcotte1,
Anna Hultberg1, Dipu Delwar1, Philip J. van Dalen2, Peter H.
Pouwels2, 3, Rob J. Leer2, 3, Charles G. Kelly4, Craig van
Dollenweerd4, Julian K. Ma4 & Lennart Hammarström1
1. Center for Oral Biology, Karolinska Institutet at NOVUM and
Division of Clinical Immunology, Karolinska Institutet at
Huddinge Hospital, SE-141 86 Huddinge, Sweden.
2. TNO Prevention and Health, Division of Immunology and
Infectious Disease, PO Box 2215, 2301 CE Leiden, The
Netherlands.
3. TNO Voeding, Department of Applied Microbiology and Gene
Technology, Postbox 370, 3600 AJ, Zeist, The Netherlands.
4. Department of Oral Medicine and Pathology, King's College
London, Guy's Hospital, London Bridge, London, UK.
Correspondence should be addressed to L Hammarström.
e-mail: lennart.hammarstrom@biosci.ki.se
Lactobacilli have previously been used to deliver vaccine
components for active immunization in vivo. Vectors encoding a
single-chain Fv (scFv) antibody fragment, which recognizes the
streptococcal antigen I/II (SAI/II) adhesion molecule of
Streptococcus mutans, were constructed and expressed in
Lactobacillus zeae (American Type Culture Collection (ATCC)
393). The scFv antibody fragments secreted into the
supernatant or expressed on the surface of the bacteria showed
binding activity against SAI/II in enzyme-linked immunosorbent
assay (ELISA), and surface scFv-expressing lactobacilli
agglutinated SAI/II-expressing S. mutans in vitro without
affecting the corresponding SAI/II knockout strain.
Lactobacilli expressing the scFv fragment fused to an E-tag
were visualized by scanning electron microscopy (SEM) using
beads coated with a monoclonal anti-E-tag antibody, and they
bound directly to beads coated with SAI/II. After
administration of scFv-expressing bacteria to a rat model of
dental caries development, S. mutans bacteria counts and
caries scores were markedly reduced. As lactobacilli are
generally regarded as safe (GRAS) microorganisms, this
approach may be of considerable commercial interest for in
vivo immunotherapy.
v20/n7/abs/nbt0 702-702.html&filetype=
July 2002 Volume 20 Number 7 pp 702 - 706
In situ delivery of passive immunity by lactobacilli producing
single-chain antibodies
Carina Krüger1, Yanzhong Hu1, Qiang Pan1, Harold Marcotte1,
Anna Hultberg1, Dipu Delwar1, Philip J. van Dalen2, Peter H.
Pouwels2, 3, Rob J. Leer2, 3, Charles G. Kelly4, Craig van
Dollenweerd4, Julian K. Ma4 & Lennart Hammarström1
1. Center for Oral Biology, Karolinska Institutet at NOVUM and
Division of Clinical Immunology, Karolinska Institutet at
Huddinge Hospital, SE-141 86 Huddinge, Sweden.
2. TNO Prevention and Health, Division of Immunology and
Infectious Disease, PO Box 2215, 2301 CE Leiden, The
Netherlands.
3. TNO Voeding, Department of Applied Microbiology and Gene
Technology, Postbox 370, 3600 AJ, Zeist, The Netherlands.
4. Department of Oral Medicine and Pathology, King's College
London, Guy's Hospital, London Bridge, London, UK.
Correspondence should be addressed to L Hammarström.
e-mail: lennart.hammarstrom@biosci.ki.se
Lactobacilli have previously been used to deliver vaccine
components for active immunization in vivo. Vectors encoding a
single-chain Fv (scFv) antibody fragment, which recognizes the
streptococcal antigen I/II (SAI/II) adhesion molecule of
Streptococcus mutans, were constructed and expressed in
Lactobacillus zeae (American Type Culture Collection (ATCC)
393). The scFv antibody fragments secreted into the
supernatant or expressed on the surface of the bacteria showed
binding activity against SAI/II in enzyme-linked immunosorbent
assay (ELISA), and surface scFv-expressing lactobacilli
agglutinated SAI/II-expressing S. mutans in vitro without
affecting the corresponding SAI/II knockout strain.
Lactobacilli expressing the scFv fragment fused to an E-tag
were visualized by scanning electron microscopy (SEM) using
beads coated with a monoclonal anti-E-tag antibody, and they
bound directly to beads coated with SAI/II. After
administration of scFv-expressing bacteria to a rat model of
dental caries development, S. mutans bacteria counts and
caries scores were markedly reduced. As lactobacilli are
generally regarded as safe (GRAS) microorganisms, this
approach may be of considerable commercial interest for in
vivo immunotherapy.