title: TLR2, but not TLR4, plays a predominant role in the immune responses to cholera vaccines.
abstract: Vibrio cholerae can cause severe diarrhea and dehydration leading to high mortality and morbidity. Current cholera vaccines are formulated with KVC. Although the innate immune responses following vaccination deeply influence the induction of adaptive immunity, the initial recognition of cholera vaccines by the host innate immune system is not well characterized. In this study, the ability of KVC to induce innate immune responses was investigated. Unlike typical Gram-negative bacteria stimulating TLR2 and TLR4, KVC activated TLR2 but hardly TLR4. However, purified V. cholerae LPS preferentially stimulated TLR4, although not as potently as LPS of other Gram-negative bacteria, implying that LPS is not a major immunostimulatory component of KVC. Instead, MPFs were similar to KVC in the capacity to activate TLR2, transcription factors, and cytokine expression. Furthermore, OmpU is an abundant membrane protein of V. cholerae and could interact with TLR2 for inducing cytokine expression. Notably, cholera vaccine-induced immune responses are impaired in TLR2(-/-) mice. Conclusively, TLR2 is essential for the immune responses to cholera vaccination, and OmpU is the major immunostimulatory component of cholera vaccines.
authors.affiliation: *Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, and Animal Science and Biotechnology Major and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do, Republic of Korea; Department of Parasitology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea; and Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Yang
authors.affiliation: *Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, and Animal Science and Biotechnology Major and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do, Republic of Korea; Department of Parasitology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea; and Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: *Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, and Animal Science and Biotechnology Major and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do, Republic of Korea; Department of Parasitology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea; and Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Seok-Seong
authors.initials: SS
authors.lastname: Kang
authors.affiliation: *Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, and Animal Science and Biotechnology Major and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do, Republic of Korea; Department of Parasitology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea; and Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kyoung Whun
authors.initials: KW
authors.lastname: Kim
authors.affiliation: *Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, and Animal Science and Biotechnology Major and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do, Republic of Korea; Department of Parasitology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea; and Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.affiliation: *Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, and Animal Science and Biotechnology Major and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do, Republic of Korea; Department of Parasitology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea; and Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.affiliation: *Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, and Animal Science and Biotechnology Major and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do, Republic of Korea; Department of Parasitology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea; and Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Soon-Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: *Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, and Animal Science and Biotechnology Major and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do, Republic of Korea; Department of Parasitology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea; and Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ho Seong
authors.initials: HS
authors.lastname: Seo
authors.affiliation: *Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, and Animal Science and Biotechnology Major and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do, Republic of Korea; Department of Parasitology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea; and Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
authors.affiliation: *Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, and Animal Science and Biotechnology Major and World Class University Biomodulation Major, Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do, Republic of Korea; Department of Parasitology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of Korea; Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Republic of Korea; and Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada shhan-mi@snu.ac.kr.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
mesh_terms: D000818:Animals; D002460:Cell Line; D022121:Cholera Vaccines / Q000276:immunology*; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*
chemical_list: D022121:Cholera Vaccines; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: OmpU; Vibrio cholerae; innate immunity