PMID- 17451817 OWN - NLM STAT- MEDLINE DCOM- 20071107 LR - 20070618 IS - 0166-3542 (Print) IS - 0166-3542 (Linking) VI - 75 IP - 3 DP - 2007 Sep TI - Enhanced protective efficacy of H5 subtype avian influenza DNA vaccine with codon optimized HA gene in a pCAGGS plasmid vector. PG - 234-41 AB - H5N1 influenza viruses have caused significant disease and deaths in various parts of the world in several species, including humans. Vaccination combined with culling can provide an attractive method for outbreak containment. Using synthesized oligos and overlapping extension PCR techniques, we constructed an H5 HA gene, optiHA, containing chicken biased codons based on the HA amino acid sequence of the highly pathogenic H5N1 virus A/goose/Guangdong/1/96 (GS/GD/96). The optiHA and wild-type HA genes were inserted into plasmids pCI or pCAGGS, and designated as pCIoptiHA, pCAGGoptiHA, pCIHA and pCAGGHA, respectively. To evaluate vaccine efficacy, groups of 3-week-old specific pathogen free (SPF) chickens were intramuscularly injected with the four plasmids. Sera were collected on a weekly basis post-vaccination (p.v.) for hemagglutination inhibition (HI) assays and neutralization (NT) antibody detection. All chickens receiving pCAGGoptiHA and pCAGGHA developed high levels of HI and NT antibodies at 3 weeks p.v., and were completely protected from lethal H5 virus challenge, while only partial protection was induced by inoculation with the other two plasmids. A second experiment was conducted to evaluate if a lower dose of the pCAGGoptiHA vaccine could be effective, results indicated that two doses of 10 microg of pCAGGoptiHA could induce complete protection in chickens against H5 lethal virus challenge. Based on our results, we conclude that construction optimization could dramatically increase the H5 HA gene DNA vaccine efficacy in chickens, and therefore, greatly decrease the dose necessary for inducing complete protection in chickens. FAU - Jiang, Yongping AU - Jiang Y AD - Animal Influenza Laboratory of the Ministry of Agriculture, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, 427 Maduan Street, Harbin 150001, People's Republic of China. FAU - Yu, Kangzhen AU - Yu K FAU - Zhang, Hongbo AU - Zhang H FAU - Zhang, Pingjing AU - Zhang P FAU - Li, Chenjun AU - Li C FAU - Tian, Guobin AU - Tian G FAU - Li, Yanbing AU - Li Y FAU - Wang, Xijun AU - Wang X FAU - Ge, Jinying AU - Ge J FAU - Bu, Zhigao AU - Bu Z FAU - Chen, Hualan AU - Chen H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070409 PL - Netherlands TA - Antiviral Res JT - Antiviral research JID - 8109699 RN - 0 (Antibodies, Viral) RN - 0 (Hemagglutinin Glycoproteins, Influenza Virus) RN - 0 (Influenza Vaccines) RN - 0 (Vaccines, DNA) SB - IM MH - Animals MH - Antibodies, Viral/blood MH - *Chickens/immunology/virology MH - Genetic Vectors MH - Hemagglutination Inhibition Tests MH - Hemagglutinin Glycoproteins, Influenza Virus/genetics/immunology MH - Influenza A Virus, H5N1 Subtype/genetics/*immunology/pathogenicity/physiology MH - Influenza Vaccines/*administration & dosage/genetics/immunology MH - Influenza in Birds/*prevention & control/virology MH - Neutralization Tests MH - Plasmids MH - Vaccines, DNA/*administration & dosage/genetics/immunology MH - Virus Shedding EDAT- 2007/04/25 09:00 MHDA- 2007/11/08 09:00 CRDT- 2007/04/25 09:00 PHST- 2006/10/12 00:00 [received] PHST- 2007/01/24 00:00 [revised] PHST- 2007/03/16 00:00 [accepted] PHST- 2007/04/25 09:00 [pubmed] PHST- 2007/11/08 09:00 [medline] PHST- 2007/04/25 09:00 [entrez] AID - S0166-3542(07)00277-X [pii] AID - 10.1016/j.antiviral.2007.03.009 [doi] PST - ppublish SO - Antiviral Res. 2007 Sep;75(3):234-41. doi: 10.1016/j.antiviral.2007.03.009. Epub 2007 Apr 9.