All eight vaccine formulations had a good safety profile. No serious adverse events were reported. The adjuvanted vaccines induced more injection-site symptoms and general symptoms than did the non-adjuvanted vaccines, but most were mild to moderate in intensity and transient in nature. The adjuvanted formulations were significantly more immunogenic than the non-adjuvanted formulations at all antigen doses. At the lowest antigenic dose (3·8 μg), immune responses for the adjuvanted vaccine against the recombinant homologous vaccine strain (A/Vietnam/1194/2004 NIBRG-14, clade 1) met or exceeded all US Food and Drug Administration and European Union licensure criteria. Furthermore, 37 of 48 (77%) participants receiving 3·8 μg of the adjuvanted vaccine seroconverted for neutralising antibodies against a strain derived by reverse genetics from a drifted H5N1 isolate (A/Indonesia/5/2005, clade 2).
Adjuvantation conferred significant antigen sparing that could increase the production capacity of pandemic influenza vaccine. Moreover, the cross-clade neutralising antibody responses recorded imply that such a vaccine could be deployed for immunisation before a pandemic.
right; padding-left:5px">de()">rc="/scidirimg/btn_xclose.gif" alt="Close" title="Close" onmouseover="javascript:this.src='/scidirimg/btn_xclose_hov.gif';" onmouseout="javascript:this.src='/scidirimg/btn_xclose.gif';"> rder=0 src="/scidirimg/jrn_nsub.gif" alt="You are not entitled to access the full text of this document" title="You are not entitled to access the full text of this document" width=12 height=14"> ref="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WXR-47GH6CJ-1T&_user=10&_coverDate=01%2F05%2F2003&_rdoc=1&_fmt=high&_orig=article&_cdi=7165&_sort=v&_docanchor=&view=c&_ct=35&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=c0615e7f7ba98afde22b4377715ff423">Evaluation of a Genetically Modified Reassortant H5N1 Influenza A Virus Vaccine Candidate Generated by Plasmidroll"> r>ref="http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WXR-47GH6CJ-1T-1&_cdi=7165&_user=10&_orig=article&_coverDate=01%2F05%2F2003&_sk=996949998&view=c&wchp=dGLbVzz-zSkWb&md5=bf18af0b99b732abc9bcbfa287e2323f&ie=/sdarticle.pdf">rtical-align:absmiddle;" border="0" src="http://www.sciencedirect.com/scidirimg/icon_pdf.gif" alt=""> Purchase PDF (99 K)Avian influenza A H5N1 viruses similar to those that infected humans in Hong Kong in 1997 continue to circulate in waterfowl and have reemerged in poultry in the region, raising concerns that these viruses could reappear in humans. The currently licensed trivalent inactivated influenza vaccines contain hemagglutinin (HA) and neuraminidase genes from epidemic strains in a background of internal genes derived from the vaccine donor strain, A/Puerto Rico/8/34 (PR8). Such reassortant candidate vaccine viruses are currently not licensed for the prevention of human infections by H5N1 influenza viruses. A transfectant H5N1/PR8 virus was generated by plasmid-based reverse genetics. The removal of the multibasic amino acid motif in the HA gene associated with high pathogenicity in chickens, and the new genotype of the H5N1/PR8 transfectant virus, attenuated the virus for chickens and mice without altering the antigenicity of the HA. A Formalin-inactivated vaccine prepared from this virus was immunogenic and protected mice from subsequent wild-type H5N1 virus challenge. This is the first successful attempt to develop an H5N1 vaccine seed virus resembling those used in currently licensed influenza A vaccines with properties that make it a promising candidate for further evaluation in humans. |
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