In situ delivery of passive immunity by lactobacilli producing single-chain antibodies.
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.
Krüger
Carina
C
Center for Oral Biology, Karolinska Institutet at NOVUM and Division of Clinical Immunology, Karolinska Institutet at Huddinge Hospital, SE-141 86 Huddinge, Sweden.
Hu
Yanzhong
Y
Pan
Qiang
Q
Marcotte
Harold
H
Hultberg
Anna
A
Delwar
Dipu
D
van Dalen
Philip J
PJ
Pouwels
Peter H
PH
Leer
Rob J
RJ
Kelly
Charles G
CG
van Dollenweerd
Craig
C
Ma
Julian K
JK
Hammarström
Lennart
L
D000818:Animals; D003731:Dental Caries / Q000276:immunology / Q000517:prevention & control; D015964:Gene Expression Regulation, Bacterial; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007780:Lacticaseibacillus casei / Q000235:genetics* / Q000276:immunology*; D008957:Models, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D013295:Streptococcus mutans / Q000276:immunology / Q000502:physiology
D007135:Immunoglobulin Variable Region