PMID- 32112797 OWN - NLM STAT- MEDLINE DCOM- 20210401 LR - 20210401 IS - 1872-9096 (Electronic) IS - 0166-3542 (Linking) VI - 177 DP - 2020 May TI - Multivalent DNA vaccine protects against genital herpes by T-cell immune induction in vaginal mucosa. PG - 104755 LID - S0166-3542(19)30444-9 [pii] LID - 10.1016/j.antiviral.2020.104755 [doi] AB - Genital herpes is one of the most common sexually transmitted infections (STIs), and it is mainly caused by the neurotropic herpes simplex virus (HSV-2). Not only does this infection cause ulcers, but HSV-2 can also stay in a latent state in the nervous system of the host throughout their lifespan. As a result, many people do not know that they harbor this infection. Moreover, HSV-2 serves as a major risk factor for human immunodeficiency virus (HIV) infection and can be transmitted to the fetus. Despite the high risk of infection and adverse effects, attempts at development of an effective vaccine for HSV-2 have not yet been successful. In this study, we developed a DNA vaccine for HSV-2 (SL-V20). This multivalent DNA vaccine effectively reduced the pathological symptoms of infection and induced efficient elimination of the virus in a mouse model. Intramuscular injection of SL-V20 led to induction of an HSV-2-specific T-cell response in the vagina, the major infection site, and in draining lymph organs. Dendritic cells (DCs), especially basic leucine zipper ATF-like transcription factor 3 (Baft3)(+) DCs and partially interferon regulatory factor 4 (Irf4)(+) DCs, were involved in this T-cell-mediated protective response, while B cells were dispensable for these prophylactic effects. This study demonstrates that SL-V20 offers a novel and effective vaccine against vaginal HSV-2 infection and may be applicable to patients, pending validation in clinical studies. CI - Copyright (c) 2020 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Kim, Hyeon Cheol AU - Kim HC AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea. FAU - Oh, Dong Sun AU - Oh DS AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea. FAU - Park, Jang Hyun AU - Park JH AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea. FAU - Kim, Hyun-Jin AU - Kim HJ AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea. FAU - Seo, Yong Bok AU - Seo YB AD - SL-VAXiGEN Inc., 700 Daewangpanyo-Ro, Bundang-Gu, Seongnam, Gyeonggi, 13488, Republic of Korea. FAU - Yoo, Hye Jee AU - Yoo HJ AD - Biomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon, 34141, Republic of Korea. FAU - Jang, Hye Seon AU - Jang HS AD - Biomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon, 34141, Republic of Korea. FAU - Shin, Jua AU - Shin J AD - SL-VAXiGEN Inc., 700 Daewangpanyo-Ro, Bundang-Gu, Seongnam, Gyeonggi, 13488, Republic of Korea. FAU - Kim, Chae Won AU - Kim CW AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea. FAU - Kwon, Myeong Seung AU - Kwon MS AD - Department of Obstetrics and Gynecology, College of Medicine, Myunggok Medical Research Center, Konyang University, Daejeon, Republic of Korea. FAU - Jin, Hyun-Tak AU - Jin HT AD - ProGen Co., Ltd, 1201, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. FAU - Lee, Sung Ki AU - Lee SK AD - Department of Obstetrics and Gynecology, College of Medicine, Myunggok Medical Research Center, Konyang University, Daejeon, Republic of Korea. FAU - Oh, Ji Eun AU - Oh JE AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea. Electronic address: jieun.oh@kaist.ac.kr. FAU - Lee, Heung Kyu AU - Lee HK AD - Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea; Biomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon, 34141, Republic of Korea; KAIST Institute for Health Science and Technology, KAIST, Daejeon, 34141, Republic of Korea. Electronic address: heungkyu.lee@kaist.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200226 PL - Netherlands TA - Antiviral Res JT - Antiviral research JID - 8109699 RN - 0 (Antibodies, Viral) RN - 0 (Vaccines, Combined) RN - 0 (Vaccines, DNA) RN - 0 (Viral Vaccines) SB - IM MH - Animals MH - Antibodies, Viral/*blood MH - Female MH - Herpes Genitalis/immunology/*prevention & control MH - Herpesvirus 2, Human MH - Mice MH - Mice, Inbred C57BL MH - T-Lymphocytes/*immunology MH - Vaccines, Combined/administration & dosage/immunology MH - Vaccines, DNA/administration & dosage/immunology MH - Vagina/*immunology MH - Viral Vaccines/administration & dosage/*immunology OTO - NOTNLM OT - DNA vaccine OT - Dendritic cells OT - Herpes simplex virus OT - Protective immunity OT - Sexually transmitted infection EDAT- 2020/03/01 06:00 MHDA- 2021/04/02 06:00 CRDT- 2020/03/01 06:00 PHST- 2019/08/06 00:00 [received] PHST- 2020/02/21 00:00 [revised] PHST- 2020/02/24 00:00 [accepted] PHST- 2020/03/01 06:00 [pubmed] PHST- 2021/04/02 06:00 [medline] PHST- 2020/03/01 06:00 [entrez] AID - S0166-3542(19)30444-9 [pii] AID - 10.1016/j.antiviral.2020.104755 [doi] PST - ppublish SO - Antiviral Res. 2020 May;177:104755. doi: 10.1016/j.antiviral.2020.104755. Epub 2020 Feb 26.