title: Immunogenicity and efficacy in mice of an adenovirus-based bicistronic rotavirus vaccine expressing NSP4 and VP7.
abstract: NSP4 and VP7 are important functional proteins of rotavirus. Proper combination of viral gene expression is favorable to improving the protection effect of subunit vaccine. In the present study, We evaluated the immunogenicity and efficacy of the bicistronic recombinant adenovirus (rAd-NSP4-VP7) and two single-gene expressing adenoviruses (rAd-NSP4, rAd-VP7). The three adenovirus vaccines were used to immunize mice by intramuscular or intranasal administration. The data showed significant increases in serum antibodies, T lymphocyte subpopulations proliferation, and cytokine secretions of splenocyte in all immunized groups. However, the serum IgA and neutralizing antibody levels of the rAd-NSP4-VP7 or rAd-VP7 groups were significantly higher than those of the rAd-NSP4, while the splenocyte numbers of IFN-γ secretion in the rAd-NSP4-VP7 or rAd-NSP4 groups was greater than that of the rAd-VP7. Furthermore, the efficacy evaluation in a suckling mice model indicated that only rAd-NSP4-VP7 conferred significant protection against rotavirus shedding challenge. These results suggest that the co-expression of NSP4 and VP7 in an adenovirus vector induce both humoral and cell-mediated immune responses efficiently, and provide potential efficacy for protection against rotavirus disease. It is possible to represent an efficacious subunits vaccine strategy for control of rotavirus infection and transmission.
authors.affiliation: Institute of Medical Biology; Chinese Academy of Medical Sciences and Peking Union Medical College; Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, Yunnan Province, PR China; Kunming University, School of Medicine, Kunming, Yunnan Province, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.affiliation: Institute of Medical Biology; Chinese Academy of Medical Sciences and Peking Union Medical College; Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, Yunnan Province, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.affiliation: Institute of Medical Biology; Chinese Academy of Medical Sciences and Peking Union Medical College; Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, Yunnan Province, PR China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Medical Biology; Chinese Academy of Medical Sciences and Peking Union Medical College; Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, Yunnan Province, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Institute of Medical Biology; Chinese Academy of Medical Sciences and Peking Union Medical College; Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, Yunnan Province, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Mi
authors.affiliation: Institute of Medical Biology; Chinese Academy of Medical Sciences and Peking Union Medical College; Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, Yunnan Province, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yan
authors.affiliation: Institute of Medical Biology; Chinese Academy of Medical Sciences and Peking Union Medical College; Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, Yunnan Province, PR China.
authors.forename: Xianglian
authors.initials: X
authors.lastname: Niu
authors.affiliation: Institute of Medical Biology; Chinese Academy of Medical Sciences and Peking Union Medical College; Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, Yunnan Province, PR China. Electronic address: lihj6912@hotmail.com.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Medical Biology; Chinese Academy of Medical Sciences and Peking Union Medical College; Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, Yunnan Province, PR China. Electronic address: maoshs@imbcams.com.cn.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Sun
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D007070:Immunoglobulin A / Q000097:blood; D007273:Injections, Intramuscular; D008813:Mice, Inbred ICR; D012400:Rotavirus Infections / Q000517:prevention & control; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D017201:Virus Shedding
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D016207:Cytokines; D004337:Drug Carriers; D007070:Immunoglobulin A; C434828:NSP5 protein, rotavirus group A; D022243:Rotavirus Vaccines; C050779:VP7 protein, Rotavirus; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins
keywords: Bicistronic; Immunogenicity; NSP4; Recombinant adenovirus; Rotavirus; VP7; Vaccine