Sublingual Administration of Bacteria-Expressed Influenza Virus Hemagglutinin 1 (HA1) Induces Protection against Infection with 2009 Pandemic H1N1 Influenza Virus

Byoung-Shik Shim; Jung-ah Choi; Ho-Hyun Song; Sung-Moo Park; In Su Cheon; Ji-Eun Jang; Sun Je Woo; Chung Hwan Cho; Min-Suk Song; Hyemi Kim; Kyung Joo Song; Jae Myun Lee; Suhng Wook Kim; Dae Sub Song; Young Ki Choi; Jae-Ouk Kim; Huan Huu Nguyen; Dong Wook Kim; Young Yil Bahk; Cheol-Heui Yun; Man Ki Song

doi:10.1007/s12275-013-2399-z

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Research Support, Non-U.S. Gov't
Sublingual Administration of Bacteria-Expressed Influenza Virus Hemagglutinin 1 (HA1) Induces Protection against Infection with 2009 Pandemic H1N1 Influenza Virus: Byoung-Shik Shim ¹, Jung-ah Choi ¹, Ho-Hyun Song ¹, Sung-Moo Park ^1,2, In Su Cheon ^1,2, Ji-Eun Jang ¹, Sun Je Woo ^1,3, Chung Hwan Cho ^1,2, Min-Suk Song ⁴, Hyemi Kim ⁵, Kyung Joo Song ⁵, Jae Myun Lee ⁵, Suhng Wook Kim ⁶, Dae Sub Song ⁷, Young Ki Choi ⁴, Jae-Ouk Kim ¹, Huan Huu Nguyen ¹, Dong Wook Kim ⁸, Young Yil Bahk ⁹, Cheol-Heui Yun ², Man Ki Song ¹; Journal of Microbiology 2013;51(1):130-135.
DOI: https://doi.org/10.1007/s12275-013-2399-z
Published online: March 2, 2013

¹Laboratory Science Division, International Vaccine Institute, Seoul 151-919, Republic of Korea , ²Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, and the Center for Agricultural Biomaterials, and Center for Food Safety and Toxicology, Seoul National University, Seoul 151-921, Republic of Korea, ³Department of Oral Microbiology and Immunology, Dental Research Institute, and BK21 Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea, ⁴College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea, ⁵Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea, ⁶Department of Biomedical Science, College of Health Sciences, Korea, ⁷Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea, ⁸Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do 426-791, Republic of Korea, ⁹Department of Biotechnology, Konkuk University, Chungju 380-701, Republic of Korea¹Laboratory Science Division, International Vaccine Institute, Seoul 151-919, Republic of Korea , ²Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, and the Center for Agricultural Biomaterials, and Center for Food Safety and Toxicology, Seoul National University, Seoul 151-921, Republic of Korea, ³Department of Oral Microbiology and Immunology, Dental Research Institute, and BK21 Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea, ⁴College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea, ⁵Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea, ⁶Department of Biomedical Science, College of Health Sciences, Korea, ⁷Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea, ⁸Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do 426-791, Republic of Korea, ⁹Department of Biotechnology, Konkuk University, Chungju 380-701, Republic of Korea

Corresponding author: Man Ki Song , Tel: +82-2-881-1404,

Received: 31 July 2012 • Accepted: 9 January 2013

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Abstract

Influenza viruses are respiratory pathogens that continue to pose a significantly high risk of morbidity and mortality of humans worldwide. Vaccination is one of the most effective strategies for minimizing damages by influenza outbreaks. In addition, rapid development and production of efficient vaccine with convenient administration is required in case of influenza pandemic. In this study, we generated recombinant influenza virus hemagglutinin protein 1 (sHA1) of 2009 pandemic influenza virus as a vaccine candidate using a wellestablished bacterial expression system and administered it into mice via sublingual (s.l.) route. We found that s.l. immunization with the recombinant sHA1 plus cholera toxin (CT) induced mucosal antibodies as well as systemic antibodies including neutralizing Abs and provided complete protection against infection with pandemic influenza virus A/CA/04/09 (H1N1) in mice. Indeed, the protection efficacy was comparable with that induced by intramuscular (i.m.) immunization route utilized as general administration route of influenza vaccine. These results suggest that s.l. vaccination with the recombinant non-glycosylated HA1 protein offers an alternative strategy to control influenza outbreaks including pandemics.

Keywords: Hemagglutinin;mucosal immune response;non-glycosylation;pandemic;sublingual

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Sublingual Administration of Bacteria-Expressed Influenza Virus Hemagglutinin 1 (HA1) Induces Protection against Infection with 2009 Pandemic H1N1 Influenza Virus

J. Microbiol. 2013;51(1):130-135. Published online March 2, 2013

DOI: https://doi.org/10.1007/s12275-013-2399-z

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