PMID- 38097457 OWN - NLM STAT- MEDLINE DCOM- 20240101 LR - 20240424 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 42 IP - 2 DP - 2024 Jan 12 TI - Intranasal immunization with the recombinant measles virus encoding the spike protein of SARS-CoV-2 confers protective immunity against COVID-19 in hamsters. PG - 69-74 LID - S0264-410X(23)01444-5 [pii] LID - 10.1016/j.vaccine.2023.12.011 [doi] AB - BACKGROUND: As the nasal mucosa is the initial site of infection for COVID-19, intranasal vaccines are more favorable than conventional vaccines. In recent clinical studies, intranasal immunization has been shown to generate higher neutralizing antibodies; however, there is a lack of evidence on sterilizing immunity in the upper airway. Previously, we developed a recombinant measles virus encoding the spike protein of SARS-CoV-2 (rMeV-S), eliciting humoral and cellular immune responses against SARS-CoV-2. OBJECTIVES: In this study, we aim to provide an experiment on nasal vaccines focusing on a measles virus platform as well as injection routes. STUDY DESIGN: Recombinant measles viruses expressing rMeV-S were prepared, and 5 x 10(5) PFUs of rMeV-S were administered to Syrian golden hamsters via intramuscular or intranasal injection. Subsequently, the hamsters were challenged with inoculations of 1 x 10(5) PFUs of SARS-CoV-2 and euthanized 4 days post-infection. Neutralizing antibodies and RBD-specific IgG in the serum and RBD-specific IgA in the bronchoalveolar lavage fluid (BALF) were measured, and SARS-CoV-2 clearance capacity was determined via quantitative reverse-transcription PCR (qRT-PCR) analysis and viral titer measurement in the upper respiratory tract and lungs. Immunohistochemistry and histopathological examinations of lung samples from experimental hamsters were conducted. RESULTS: The intranasal immunization of rMeV-S elicits protective immune responses and alleviates virus-induced pathophysiology, such as body weight reduction and lung weight increase in hamsters. Furthermore, lung immunohistochemistry demonstrated that intranasal rMeV-S immunization induces effective SARS-CoV-2 clearance that correlates with viral RNA content, as determined by qRT-PCR, in the lung and nasal wash samples, SARS-CoV-2 viral titers in lung, nasal wash, BALF samples, serum RBD-specific IgG concentration, and RBD-specific IgA concentration in the BALF. CONCLUSION: An intranasal vaccine based on the measles virus platform is a promising strategy owing to the typical route of infection of the virus, the ease of administration of the vaccine, and the strong immune response it elicits. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Park, Sang-In AU - Park SI AD - SML Biopharm, Gwangmyeong, Republic of Korea. FAU - Park, Sohyun AU - Park S AD - Chungbuk National University, Cheongju, Republic of Korea. FAU - Lee, Kunse AU - Lee K AD - SK Bioscience, Seongnam, Republic of Korea. FAU - Kwak, Hye Won AU - Kwak HW AD - SML Biopharm, Gwangmyeong, Republic of Korea; The Catholic University of Korea, Bucheon, Republic of Korea. FAU - Kim, Yong Kwan AU - Kim YK AD - SML Biopharm, Gwangmyeong, Republic of Korea. FAU - Park, Hyeong-Jun AU - Park HJ AD - SML Biopharm, Gwangmyeong, Republic of Korea; The Catholic University of Korea, Bucheon, Republic of Korea. FAU - Bang, Yoo-Jin AU - Bang YJ AD - The Catholic University of Korea, Bucheon, Republic of Korea. FAU - Kim, Jae-Yong AU - Kim JY AD - The Catholic University of Korea, Bucheon, Republic of Korea. FAU - Kim, Daegeun AU - Kim D AD - SML Biopharm, Gwangmyeong, Republic of Korea. FAU - Seo, Ki-Weon AU - Seo KW AD - SK Bioscience, Seongnam, Republic of Korea. FAU - Lee, Su Jeen AU - Lee SJ AD - SK Bioscience, Seongnam, Republic of Korea. FAU - Kim, Hun AU - Kim H AD - SK Bioscience, Seongnam, Republic of Korea. FAU - Kim, Yeonhwa AU - Kim Y AD - Chungbuk National University, Cheongju, Republic of Korea. FAU - Kim, Do-Hyung AU - Kim DH AD - SML Biopharm, Gwangmyeong, Republic of Korea; The Catholic University of Korea, Bucheon, Republic of Korea. FAU - Park, Hyo-Jung AU - Park HJ AD - The Catholic University of Korea, Bucheon, Republic of Korea. FAU - Jung, Seo-Yeon AU - Jung SY AD - SK Bioscience, Seongnam, Republic of Korea. FAU - Ga, Eulhae AU - Ga E AD - Chonnam National University, Gwangju, Republic of Korea. FAU - Hwang, Jaehyun AU - Hwang J AD - Chonnam National University, Gwangju, Republic of Korea. FAU - Na, Woonsung AU - Na W AD - Chonnam National University, Gwangju, Republic of Korea. FAU - Hong, So-Hee AU - Hong SH AD - Ewha Womans University, Seoul, Republic of Korea. FAU - Lee, Sang-Myeong AU - Lee SM AD - Chungbuk National University, Cheongju, Republic of Korea. Electronic address: smlee@chungbuk.ac.kr. FAU - Nam, Jae-Hwan AU - Nam JH AD - The Catholic University of Korea, Bucheon, Republic of Korea. Electronic address: jhnam@catholic.ac.kr. LA - eng PT - Journal Article DEP - 20231214 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (spike protein, SARS-CoV-2) RN - 0 (Spike Glycoprotein, Coronavirus) RN - 0 (Antibodies, Neutralizing) RN - 0 (Vaccines) RN - 0 (Immunoglobulin A) RN - 0 (Immunoglobulin G) RN - 0 (Antibodies, Viral) SB - IM MH - Animals MH - Cricetinae MH - SARS-CoV-2 MH - Measles virus/genetics MH - *COVID-19/prevention & control MH - Spike Glycoprotein, Coronavirus MH - Immunization MH - *Measles MH - *Orthopoxvirus MH - Nasal Mucosa MH - Antibodies, Neutralizing MH - *Vaccines MH - Immunoglobulin A MH - Immunoglobulin G MH - Antibodies, Viral MH - Administration, Intranasal OTO - NOTNLM OT - Intranasal vaccination OT - Measles virus vector OT - Messenger RNA OT - SARS-CoV-2 COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/12/15 00:43 MHDA- 2024/01/02 11:42 CRDT- 2023/12/14 21:59 PHST- 2023/04/22 00:00 [received] PHST- 2023/10/12 00:00 [revised] PHST- 2023/12/02 00:00 [accepted] PHST- 2024/01/02 11:42 [medline] PHST- 2023/12/15 00:43 [pubmed] PHST- 2023/12/14 21:59 [entrez] AID - S0264-410X(23)01444-5 [pii] AID - 10.1016/j.vaccine.2023.12.011 [doi] PST - ppublish SO - Vaccine. 2024 Jan 12;42(2):69-74. doi: 10.1016/j.vaccine.2023.12.011. Epub 2023 Dec 14.