title: Nizatidine, a small molecular compound, enhances killed H5N1 vaccine cell-mediated responses and protects mice from lethal viral challenge.
abstract: Nizatidine (NIZ), closely related to Cimetidine, is a histamine H2 receptor inverse agonist used primarily as an anti-acid drug. Recent studies showed that this class of compounds may also modulate immune responses. To evaluate adjuvant effects of NIZ on vaccine immune modulation, we formulated NIZ with a H5N1 killed viral antigen and tested in vitro and in vivo. NIZ activated DC maturation and stimulated Th1 and Th2 immune responses to H5N1 vaccine. As a result, it enhanced both antibody and T cell-mediated immune responses. We also observed that a single immunization into C57BL/6 mice blocked IL-10 upregulation and potentiated Th1/Th2 dual polarization. Importantly, the inoculation of H5N1 vaccine with NIZ significantly improved protection of animals from death after challenge and reduced virus loads in the lung tissues. Considering its water-soluble nature, compared with Cimetidine, Nizatidine may be a better choice to use as a vaccine adjuvant.
authors.affiliation: State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University; Beijing, PR China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University; Beijing, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine; China Agricultural University; Beijing, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xue
authors.affiliation: College of Veterinary Medicine; China Agricultural University; Beijing, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Dahuanong Animal Health Inc.; Guangdong, PR China.
authors.forename: Ruiai
authors.initials: R
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University; Beijing, PR China; Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College; Shanghai, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008810:Mice, Inbred C57BL; D016567:Nizatidine / Q000008:administration & dosage / Q000494:pharmacology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D016567:Nizatidine
keywords: Cimetidine; H5N1 vaccine; Nizatidine; adjuvant; killed viral antigen