title: A DNA vaccine encoding VP22 of herpes simplex virus type I (HSV-1) and OprF confers enhanced protection from Pseudomonas aeruginosa in mice.
abstract: Pseudomonas aeruginosa antimicrobial resistance is a major therapeutic challenge. DNA vaccination is an attractive approach for antigen-specific immunotherapy against P. aeruginosa. We explored the feasibility of employing Herpes simplex virus type 1 tegument protein, VP22, as a molecular tool to enhance the immunogenicity of an OprF DNA vaccine against P. aeruginosa. Recombinant DNA vaccines, pVAX1-OprF, pVAX1-OprF-VP22 (encoding a n-OprF-VP22-c fusion protein) and pVAX1-VP22-OprF (encoding a n-VP22-OprF-c fusion protein) were constructed. The humoral and cellular immune responses and immune protective effects of these DNA vaccines in mice were evaluated. In this report, we showed that vaccination with pVAX1-OprF-VP22 induced higher levels of IgG titer, T cell proliferation rate. It also provided better immune protection against the P. aeruginosa challenge when compared to that induced by pVAX1-OprF or pVAX1-VP22-OprF DNA vaccines. Molecular mechanistic analyses indicated vaccination with pVAX1-OprF-VP22 triggered immune responses characterized by a preferential increase in antigen specific IgG2a and IFN-γ in mice, indicating Th1 polarization. We concluded that VP22 is a potent stimulatory molecular tool for DNA vaccination when fused to the carboxyl end of OprF gene. Our study provides a novel strategy for prevention and treatment of P. aeruginosa infection.
authors.affiliation: Department of Pharmacy, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, PR China. Electronic address: xiannyyu@gmail.com.
authors.forename: Xian
authors.initials: X
authors.lastname: Yu
authors.affiliation: Institute of Materia Medica, North Sichuan Medical College, Nanchong 637007, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Chongqing General Hospital, Chongqing 400014, PR China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Institute of Materia Medica, North Sichuan Medical College, Nanchong 637007, PR China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Materia Medica, North Sichuan Medical College, Nanchong 637007, PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Institute of Materia Medica, North Sichuan Medical College, Nanchong 637007, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lei
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D005260:Female; D018259:Herpesvirus 1, Human; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011552:Pseudomonas Infections / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D015678:Viral Structural Proteins / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; C547605:OprF protein, Pseudomonas aeruginosa; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22; D007371:Interferon-gamma
keywords: Cell-penetrating peptides; DNA vaccine; Immunogenicity; OprF; Pseudomonas aeruginosa; VP22