title: Employing XIAP to enhance the duration of antigen expression and immunity against an avian influenza H5 DNA vaccine.
abstract: DNA vaccine represents a powerful approach for prevention of avian H5N1 influenza infection. Yet, DNA vaccine-induced immune responses might be limited by the short duration of antigen expression. As a strategy to enhance adaptive immune responses elicited by a hemagglutinin 5 (H5) DNA vaccine, we explored the effect of co-administration of a DNA encoding X-linked inhibitor of apoptosis protein (XIAP) as a modulator of apoptosis and a stimulator of inflammatory signaling. In cultured cells as early as 24 hours (h), we found that the DNA vaccine encoded H5 antigen was a potent stimulator of apoptosis, and the H5 pro-apoptotic activity was significantly suppressed by the co-expression of full-length XIAP or mutant XIAP (ΔRING). However, full-length XIAP showed a higher potency than mutant XIAP (ΔRING) in the inhibition of H5-induced apoptosis. We also compared the immunizing ability of transmembrane and secretory forms of H5. Mice vaccinated (twice with 3-week intervals) with the secretory form of H5 showed higher hemagglutination inhibition (HI) antibody titers than mice vaccinated with the transmembrane form of H5. Furthermore, co-administration of XIAP with the secretory form of H5 resulted into a stronger antibody response than the transmembrane form of H5. Our findings suggest that in the design of DNA vaccines for a given pro-apoptotic antigen, using an anti-apoptotic molecular adjuvant and the secretory form of antigen may be a greater stimulus to induce immune responses.
authors.affiliation: Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad , Mashhad , Iran .
authors.forename: Seyed-Elias
authors.initials: SE
authors.lastname: Tabatabaeizadeh
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Bassami
authors.forename: Alireza
authors.initials: A
authors.lastname: Haghparast
authors.forename: Hesam
authors.initials: H
authors.lastname: Dehghani
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D017209:Apoptosis; D001717:Birds; D016466:CHO Cells; D003412:Cricetulus; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics; D056724:Immunity, Humoral; D007114:Immunization; D053124:Influenza A Virus, H5N1 Subtype / Q000502:physiology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000235:genetics; D005585:Influenza in Birds / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000008:administration & dosage*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D051636:X-Linked Inhibitor of Apoptosis Protein; C109963:hemagglutinin, avian influenza A virus
keywords: Apoptosis; DNA vaccine; XIAP; avian H5N1 influenza