title: Enhanced mucosal immune responses induced by a combined candidate mucosal vaccine based on Hepatitis A virus and Hepatitis E virus structural proteins linked to tuftsin.
abstract: Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are the most common causes of infectious hepatitis. These viruses are spread largely by the fecal-oral route and lead to clinically important disease in developing countries. To evaluate the potential of targeting hepatitis A and E infection simultaneously, a combined mucosal candidate vaccine was developed with the partial open reading frame 2 (ORF2) sequence (aa 368-607) of HEV (HE-ORF2) and partial virus protein 1 (VP1) sequence (aa 1-198) of HAV (HA-VP1), which included the viral neutralization epitopes. Tuftsin is an immunostimulatory peptide which can enhance the immunogenicity of a protein by targeting it to macrophages and dendritic cells. Here, we developed a novel combined protein vaccine by conjugating tuftsin to HE-ORF2 and HA-VP1 and used synthetic CpG oligodeoxynucleotides (ODNs) as the adjuvant. Subsequent experiments in BALB/c mice demonstrated that tuftsin enhanced the serum-specific IgG and IgA antibodies against HEV and HAV at the intestinal, vaginal and pulmonary interface when delivered intranasally. Moreover, mice from the intranasally immunized tuftsin group (HE-ORF2-tuftsin + HA-VP1-tuftsin + CpG) showed higher levels of IFN-γ-secreting splenocytes (Th1 response) and ratio of CD4+/CD8+ T cells than those of the no-tuftsin group (HE-ORF2 + HA-VP1 + CpG). Thus, the tuftsin group generated stronger humoral and cellular immune responses compared with the no-tuftsin group. Moreover, enhanced responses to the combined protein vaccine were obtained by intranasal immunization compared with intramuscular injection. By integrating HE-ORF2, HA-VP1 and tuftsin in a vaccine, this study validated an important concept for further development of a combined mucosal vaccine against hepatitis A and E infection.
authors: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Yan
authors: Y
authors: Gao
authors: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Qiudong
authors: Q
authors: Su
authors: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Yao
authors: Y
authors: Yi
authors: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Zhiyuan
authors: Z
authors: Jia
authors: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Hao
authors: H
authors: Wang
authors: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Xuexin
authors: X
authors: Lu
authors: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Feng
authors: F
authors: Qiu
authors: National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors: Shengli
authors: S
authors: Bi
mesh_terms: D000818:Animals; D005260:Female; D030041:Hepatitis A virus / Q000235:genetics / Q000276:immunology*; D006508:Hepatitis Antibodies / Q000276:immunology; D016751:Hepatitis E / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014405:Tuftsin / Q000235:genetics / Q000276:immunology*; D017778:Vaccines, Combined / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D015678:Viral Structural Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D006508:Hepatitis Antibodies; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D017778:Vaccines, Combined; D014761:Viral Hepatitis Vaccines; D015678:Viral Structural Proteins; D014405:Tuftsin