title: A Recombinant G Protein Plus Cyclosporine A-Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease.
abstract: Respiratory syncytial virus (RSV) infection can cause severe disease in the lower respiratory tract of infants and older people. Vaccination with a formalin-inactivated RSV vaccine (FI-RSV) and subsequent RSV infection has led to mild to severe pneumonia with two deaths among vaccinees. The vaccine-enhanced disease (VED) was recently demonstrated to be due to an elevated level of Th2 cell responses following loss of regulatory T (Treg) cells from the lungs. To induce high levels of neutralizing Abs and minimize pathogenic T cell responses, we developed a novel strategy of immunizing animals with a recombinant RSV G protein together with cyclosporine A. This novel vaccine induced not only a higher level of neutralizing Abs against RSV infection, but, most importantly, also significantly higher levels of Treg cells that suppressed VED in the lung after RSV infection. The induced responses provided protection against RSV challenge with no sign of pneumonia or bronchitis. Treg cell production of IL-10 was one of the key factors to suppress VED. These finding indicate that G protein plus cyclosporine A could be a promising vaccine against RSV infection in children and older people.
authors.affiliation: Key Laboratory of Medical Molecular Virology of the Ministry of Health and the Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 201508, China;
authors.forename: Chaofan
authors.identifier: http://orcid.org/0000-0002-5426-1498
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Medical Molecular Virology of the Ministry of Health and the Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 201508, China;
authors.forename: Xian
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Medical Molecular Virology of the Ministry of Health and the Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 201508, China;
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Division for Respiratory Viral Vaccines of National Institutes for Food and Drug Control, Beijing 100050, China; and.
authors.forename: Changgui
authors.initials: C
authors.lastname: Li
authors.affiliation: Beijing Advaccine Biotechnology Company, Ltd., Beijing 100085, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Dong
authors.affiliation: Beijing Advaccine Biotechnology Company, Ltd., Beijing 100085, China.
authors.forename: Zhonghuai
authors.initials: Z
authors.lastname: He
authors.affiliation: Key Laboratory of Medical Molecular Virology of the Ministry of Health and the Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 201508, China;
authors.forename: Shuren
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Molecular Virology of the Ministry of Health and the Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 201508, China; bwang3@fudan.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D016572:Cyclosporine / Q000276:immunology* / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D022261:Respiratory Syncytial Virus Vaccines; D016572:Cyclosporine; D019204:GTP-Binding Proteins