title: Novel recombinant DNA vaccine candidates for human respiratory syncytial virus: Preclinical evaluation of immunogenicity and protection efficiency.
abstract: The development of safe and potent vaccines for human respiratory syncytial virus (HRSV) is still a challenge for researchers worldwide. DNA-based immunization is currently a promising approach that has been used to generate human vaccines for different age groups. In this study, novel HRSV DNA vaccine candidates were generated and preclinically tested in BALB/c mice. Three different versions of the codon-optimized HRSV fusion (F) gene were individually cloned into the pPOE vector. The new recombinant vectors either express full-length (pPOE-F), secretory (pPOE-TF), or M282-90linked (pPOE-FM2) forms of the F protein. Distinctive expression of the F protein was identified in HEp-2 cells transfected with the different recombinant vectors using ELISA and immunofluorescence. Mice immunization verified the potential for recombinant vectors to elicit significant levels of neutralizing antibodies and CD8+T-cell lymphocytes. pPOE-TF showed higher levels of gene expression in cell culture and better induction of the humoral and cellular immune responses. Following virus challenge, mice that had been immunized with the recombinant vectors were able to control virus replication and displayed lower inflammation compared with mice immunized with empty pPOE vector or formalin-inactivated HRSV vaccine. Moreover, pulmonary cytokine profiles of mice immunized with the 3 recombinant vectors were similar to those of the mock infected group. In conclusion, recombinant pPOE vectors are promising HRSV vaccine candidates in terms of their safety, immunogenicity and protective efficiency. These data encourage further evaluation in phase I clinical trials.
authors.affiliation: a Department of Botany and Microbiology , College of Science, King Saud University , Riyadh , Saudi Arabia.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Farrag
authors.affiliation: a Department of Botany and Microbiology , College of Science, King Saud University , Riyadh , Saudi Arabia.|b Department of Virology , Faculty of Veterinary Medicine, Cairo University , Giza , Egypt.
authors.forename: Haitham M
authors.initials: HM
authors.lastname: Amer
authors.affiliation: c Institute of Nano- and Biotechnology, Department of Chemistry and Biotechnology , Aachen University of Applied Sciences , Juelich , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Öhlschläger
authors.affiliation: a Department of Botany and Microbiology , College of Science, King Saud University , Riyadh , Saudi Arabia.
authors.forename: Maaweya E
authors.initials: ME
authors.lastname: Hamad
authors.affiliation: a Department of Botany and Microbiology , College of Science, King Saud University , Riyadh , Saudi Arabia.
authors.forename: Fahad N
authors.initials: FN
authors.lastname: Almajhdi
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D008807:Mice, Inbred BALB C; D017863:Potexvirus; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D022261:Respiratory Syncytial Virus Vaccines; D019444:Vaccines, DNA; D014760:Viral Fusion Proteins
keywords: DNA vaccine; disease enhancement; fusion protein; human respiratory syncytial virus; pPOE vector; truncated form