Miyuki Tozuka1, Tatsuya Oka1, Nao Jounai1, Gyohei Egawa2, Ken J Ishii3, Kenji Kabashima2, Fumihiko Takeshita4. 1. Kitasato Daiichi Sankyo Vaccine Co., Ltd., 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan. 2. Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Syogoin-Kawaramachi, Sakyo-ku, Kyoto 606-8507, Japan. 3. Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki City, Osaka 567-0085, Japan. 4. Daiichi Sankyo Co., Ltd., 3-5-1 Nihonbashi Honcho, Chuo-ku, Tokyo 103-8426, Japan. Electronic address: takeshita.fumihiko.aw@daiichisankyo.co.jp.
Abstract
BACKGROUND: It has been clinically demonstrated that intradermal (ID) vaccines have a potential to confer a superior immunogenic profile compared to intramuscular (IM) or subcutaneous (SC) vaccines. In terms of distribution of a vaccine antigen depending on the administration routes, at least two independent immunogenic pathways of the vaccines have been proposed: (1) the antigen recognition by the immune cells present at the vaccine-administered site and (2) the antigen recognition by the lymph node (LN)-resident immune cells through the lymphatic flow from the vaccine-administered site after the antigen is directly delivered into the draining LNs. OBJECTIVE: In order to clarify the key components for the immunogenic pathway of the ID vaccine, the correlation between the kinetics of the antigen distribution to the draining LNs and antibody responses to the antigen were evaluated. METHODS: We compared the antibody responses in the groups with by surgical removal of the administration site immediately after the ID administration, and by surgical removal of the draining LNs before the ID administration. RESULTS: The results suggested that the efficient and direct antigen delivery to the draining LNs plays an important role in the antibody responses to the ID vaccine. Indeed, it was confirmed that the direct administration into the draining LNs with the antigen elicited comparable levels of the antibody responses with the ID vaccine. At the cellular level, it was shown that the LN-resident immune cells such as B cells, dendritic cells, and macrophages including medullary macrophages and subcapsular sinus macrophages interacting with the antigens following the ID administration. Finally, we demonstrated by immunofluorescence analysis that the lymphatic vessels are more diffusely distributed in the dermis as compared with the subcutaneous area and muscle. CONCLUSION: The results of the present study suggested that the skin is an optimal tissue to facilitate the vaccine antigen access to the draining LNs, which is an important immunogenic pathway of the ID vaccine. Further elucidation of regulatory mechanisms underlying such an immunogenic pathway of the ID vaccine would provide us with elements for the development of novel adjuvants and devices to enhance the immunogenicity of the ID vaccines.
BACKGROUND: It has been clinically demonstrated that intradermal (ID) vaccines have a potential to confer a superior immunogenic profile compared to intramuscular (IM) or subcutaneous (SC) vaccines. In terms of distribution of a vaccine antigen depending on the administration routes, at least two independent immunogenic pathways of the vaccines have been proposed: (1) the antigen recognition by the immune cells present at the vaccine-administered site and (2) the antigen recognition by the lymph node (LN)-resident immune cells through the lymphatic flow from the vaccine-administered site after the antigen is directly delivered into the draining LNs. OBJECTIVE: In order to clarify the key components for the immunogenic pathway of the ID vaccine, the correlation between the kinetics of the antigen distribution to the draining LNs and antibody responses to the antigen were evaluated. METHODS: We compared the antibody responses in the groups with by surgical removal of the administration site immediately after the ID administration, and by surgical removal of the draining LNs before the ID administration. RESULTS: The results suggested that the efficient and direct antigen delivery to the draining LNs plays an important role in the antibody responses to the ID vaccine. Indeed, it was confirmed that the direct administration into the draining LNs with the antigen elicited comparable levels of the antibody responses with the ID vaccine. At the cellular level, it was shown that the LN-resident immune cells such as B cells, dendritic cells, and macrophages including medullary macrophages and subcapsular sinus macrophages interacting with the antigens following the ID administration. Finally, we demonstrated by immunofluorescence analysis that the lymphatic vessels are more diffusely distributed in the dermis as compared with the subcutaneous area and muscle. CONCLUSION: The results of the present study suggested that the skin is an optimal tissue to facilitate the vaccine antigen access to the draining LNs, which is an important immunogenic pathway of the ID vaccine. Further elucidation of regulatory mechanisms underlying such an immunogenic pathway of the ID vaccine would provide us with elements for the development of novel adjuvants and devices to enhance the immunogenicity of the ID vaccines.
Authors: Mario Amacker; Charli Smardon; Laura Mason; Jack Sorrell; Kirk Jeffery; Michael Adler; Farien Bhoelan; Olga Belova; Mark Spengler; Beena Punnamoottil; Markus Schwaller; Olivia Bonduelle; Behazine Combadière; Toon Stegmann; Andrew Naylor; Richard Johnson; Desmond Wong; Sylvain Fleury Journal: NPJ Vaccines Date: 2020-05-18 Impact factor: 7.344
Authors: Tobias L Freitag; Joseph R Podojil; Ryan M Pearson; Frank J Fokta; Cecilia Sahl; Marcel Messing; Leif C Andersson; Katarzyna Leskinen; Päivi Saavalainen; Lisa I Hoover; Kelly Huang; Deborah Phippard; Sanaz Maleki; Nicholas J C King; Lonnie D Shea; Stephen D Miller; Seppo K Meri; Daniel R Getts Journal: Gastroenterology Date: 2020-02-04 Impact factor: 22.682
Authors: Jayendra Kumar Krishnaswamy; Samuel Alsén; Ulf Yrlid; Stephanie C Eisenbarth; Adam Williams Journal: Front Immunol Date: 2018-09-27 Impact factor: 7.561
Authors: Mario Amacker; Charli Smardon; Laura Mason; Jack Sorrell; Kirk Jeffery; Michael Adler; Farien Bhoelan; Olga Belova; Mark Spengler; Beena Punnamoottil; Markus Schwaller; Olivia Bonduelle; Behazine Combadière; Toon Stegmann; Andrew Naylor; Richard Johnson; Desmond Wong; Sylvain Fleury Journal: NPJ Vaccines Date: 2020-05-18 Impact factor: 7.344