title: Development of safe and effective RSV vaccine by modified CD4 epitope in G protein core fragment (Gcf).
abstract: Respiratory syncytial virus (RSV) is a major cause of respiratory tract infection in infants and young children worldwide, but currently no safe and effective vaccine is available. The RSV G glycoprotein (RSVG), a major attachment protein, is an important target for the induction of protective immune responses during RSV infection. However, it has been thought that a CD4+ T cell epitope (a.a. 183-195) within RSVG is associated with pathogenic pulmonary eosinophilia. To develop safe and effective RSV vaccine using RSV G protein core fragment (Gcf), several Gcf variants resulting from modification to CD4+ T cell epitope were constructed. Mice were immunized with each variant Gcf, and the levels of RSV-specific serum IgG were measured. At day 4 post-challenge with RSV subtype A or B, lung viral titers and pulmonary eosinophilia were determined and changes in body weight were monitored. With wild type Gcf derived from RSV A2 (wtAGcf), although RSV A subtype-specific immune responses were induced, vaccine-enhanced disease characterized by excessive pulmonary eosinophil recruitment and body weight loss were evident, whereas wtGcf from RSV B1 (wtBGcf) induced RSV B subtype-specific immune responses without the signs of vaccine-enhanced disease. Mice immunized with Th-mGcf, a fusion protein consisting CD4+ T cell epitope from RSV F (F51-66) conjugated to mGcf that contains alanine substitutions at a.a. position 185 and 188, showed higher levels of RSV-specific IgG response than mice immunized with mGcf. Both wtAGcf and Th-mGcf provided complete protection against RSV A2 and partial protection against RSV B. Importantly, mice immunized with Th-mGcf did not develop vaccine-enhanced disease following RSV challenge. Immunization of Th-mGcf provided protection against RSV infection without the symptom of vaccine-enhanced disease. Our study provides a novel strategy to develop a safe and effective mucosal RSV vaccine by manipulating the CD4+ T cell epitope within RSV G protein.
authors.affiliation: Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; World Class University Biomodulation Major and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: In Su
authors.initials: IS
authors.lastname: Cheon
authors.affiliation: Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Byoung-Shik
authors.initials: BS
authors.lastname: Shim
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; World Class University Biomodulation Major and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sung-Moo
authors.initials: SM
authors.lastname: Park
authors.affiliation: Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea; Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Jang
authors.affiliation: Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Dae Im
authors.initials: DI
authors.lastname: Jung
authors.affiliation: Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Jae-Ouk
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea; World Class University Biomodulation Major and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.affiliation: Laboratory Sciences Division, International Vaccine Institute, Seoul, Republic of Korea.
authors.forename: Man Ki
authors.initials: MK
authors.lastname: Song
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D051379:Mice; D022261:Respiratory Syncytial Virus Vaccines / Q000009:adverse effects / Q000276:immunology*; D012449:Safety; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; C502275:G glycoprotein, Respiratory syncytial virus; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins
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