@article{stoeker_nordone_gunderson_zhang_kajikawa_lavoy_miller_klaenhammer_dean_2011, title={Assessment of Lactobacillus gasseri as a Candidate Oral Vaccine Vector}, volume={18}, ISSN={["1556-6811"]}, DOI={10.1128/cvi.05277-11}, abstractNote={ABSTRACT Lactobacillus species are commensal bacteria that have long been recognized as probiotic microbes and are generally regarded as safe (GRAS) for human consumption. We have investigated the use of L. gasseri as a vaccine vector for oral immunization against mucosal pathogens. Recent research has shown that the immune response to different lactobacilli can vary widely depending on the species or subspecies of Lactobacillus being studied. While some lactobacilli seem to induce oral tolerance, others induce an adaptive immune response. This study characterized the systemic and mucosal immune response to wild-type and genetically modified L. gasseri. L. gasseri primarily activates TLR2/6, with additional activation through the TLR2 homodimer. To expand the Toll-like receptor (TLR) activation profile of L. gasseri and the immunogenicity of the vector, a plasmid containing fliC, the gene encoding bacterial flagellin, was introduced which resulted in the strong activation of TLR5. The treatment of human myeloid dendritic cells with recombinant lactobacilli expressing flagellin triggered phenotypic maturation and the release of proinflammatory cytokines. In contrast, bacterial treatment also resulted in a statistically significant increase in IL-10 production. In vivo studies established that treatment with L. gasseri led to a diversification of B-cell populations in the lamina propria of the murine colon. Furthermore, treatment with genetically modified L. gasseri led to a significant decrease in the percentage of FoxP3+ colonic lymphocytes. Taken together, these data clarify the interaction of L. gasseri with the host immune system and support further investigation of the in vivo immunogenicity of L. gasseri expressing both flagellin and candidate vaccine antigens.}, number={11}, journal={CLINICAL AND VACCINE IMMUNOLOGY}, author={Stoeker, Laura and Nordone, Shila and Gunderson, Sara and Zhang, Lin and Kajikawa, Akinobu and LaVoy, Alora and Miller, Michael and Klaenhammer, Todd R. and Dean, Gregg A.}, year={2011}, month={Nov}, pages={1834–1844} }
 @article{kajikawa_nordone_zhang_stoeker_lavoy_klaenhammer_dean_2011, title={Dissimilar Properties of Two Recombinant Lactobacillus acidophilus Strains Displaying Salmonella FliC with Different Anchoring Motifs}, volume={77}, ISSN={["0099-2240"]}, DOI={10.1128/aem.05153-11}, abstractNote={ABSTRACT Display of heterologous antigens on the cell surface is considered a useful technique for vaccine delivery by recombinant lactobacilli. In this study, two recombinant Lactobacillus acidophilus derivatives displaying Salmonella flagellin (FliC) were constructed using different anchor motifs. In one instance, the FliC protein was fused to the C-terminal region of a cell envelope proteinase (PrtP) and was bound to the cell wall by electrostatic bonds. In the other case, the same antigen was conjugated to the anchor region of mucus binding protein (Mub) and was covalently associated with the cell wall by an LPXTG motif. These two recombinant L. acidophilus cell surface displays resulted in dissimilar maturation and cytokine production by human myeloid dendritic cells. The surface-associated antigen was highly sensitive to simulated gastric and small intestinal juices. By supplementation with bicarbonate buffer and soybean trypsin inhibitor, the cell surface antigen was protected from proteolytic enzymes during gastric challenge in vitro. The protective reagents also increased the viability of the L. acidophilus cells upon challenge with simulated digestive juices. These results demonstrate the importance of protecting cells and their surface-associated antigens during oral immunization.}, number={18}, journal={APPLIED AND ENVIRONMENTAL MICROBIOLOGY}, author={Kajikawa, Akinobu and Nordone, Shila K. and Zhang, Lin and Stoeker, Laura L. and LaVoy, Alora S. and Klaenhammer, Todd R. and Dean, Gregg A.}, year={2011}, month={Sep}, pages={6587–6596} }
 @article{kajikawa_masuda_katoh_igimi_2010, title={Adjuvant Effects for Oral Immunization Provided by Recombinant Lactobacillus casei Secreting Biologically Active Murine Interleukin-1 beta}, volume={17}, ISSN={["1556-679X"]}, DOI={10.1128/CVI.00337-09}, abstractNote={ABSTRACT Vaccine delivery systems using lactic acid bacteria are under development, but their efficiency is insufficient. Autologous cytokines, such as interleukin-1β (IL-1β), are potential adjuvants for mucosal vaccines and can be provided by recombinant lactic acid bacteria. The aim of this study was the construction and evaluation of recombinant Lactobacillus casei producing IL-1β as an adjuvant delivery agent. The recombinant strain was constructed using an expression/secretion vector plasmid, including a mature IL-1β gene from mouse. The biological activity of the cytokine was confirmed by IL-8 production from Caco-2 cells. In response to the recombinant L. casei secreting IL-1β, expression of IL-6 was detected in vivo using a ligated-intestinal-loop assay. The release of IL-6 from Peyer's patch cells was also detected in vitro. Intragastric immunization with heat-killed Salmonella enterica serovar Enteritidis (SE) in combination with IL-1β-secreting lactobacilli resulted in relatively high SE-specific antibody production. In this study, it was demonstrated that recombinant L. casei secreting bioactive murine IL-1β provided adjuvant effects for intragastric immunization.}, number={1}, journal={CLINICAL AND VACCINE IMMUNOLOGY}, author={Kajikawa, Akinobu and Masuda, Kazuya and Katoh, Mitsunori and Igimi, Shizunobu}, year={2010}, month={Jan}, pages={43–48} }
 @article{kajikawa_ichikawa_igimi_2010, title={Development of a highly efficient protein-secreting system in recombinant Lactobacillus casei}, volume={20}, number={2}, journal={Journal of Microbiology and Biotechnology}, author={Kajikawa, A. and Ichikawa, E. and Igimi, S.}, year={2010}, pages={375–382} }
 @article{kajikawa_igimi_2010, title={Innate and acquired immune responses induced by recombinant Lactobacillus casei displaying flagellin-fusion antigen on the cell-surface}, volume={28}, ISSN={["1873-2518"]}, DOI={10.1016/j.vaccine.2010.02.077}, abstractNote={Bacterial flagellins are known as antigens that induce innate immune responses through TLR5 and boost immune responses in combination with other antigens. The aim of the present study was to determine the immunological properties of recombinant Lactobacillus casei producing flagellin and flagellin-fusion antigens in vitro and in vivo. Recombinant lactobacilli expressing Salmonella FliC and FliC fused to truncated SipC on the cell-surface were constructed. Fusion and non-fusion flagellin associated with L. casei retained the ability to induce IL-8 production by Caco-2 cells. Immunization of mice with these recombinant strains induced antigen-specific antibodies and cytokine production. The results showed that the outside epitope of the heterologous antigen was recognized more easily by the immune system than the inside epitope. The immune responses elicited by the Lactobacillus-associated antigens were mainly Th1 while that by the soluble antigen was Th2, although some of the responses were mixed.}, number={19}, journal={VACCINE}, author={Kajikawa, Akinobu and Igimi, Shizunobu}, year={2010}, month={Apr}, pages={3409–3415} }