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Inactivated and adjuvanted whole-virion clade 2.3.4 H5N1 pre-pandemic influenza vaccine possesses broad protective efficacy against infection by heterologous clades of highly pathogenic H5N1 avian influenza virus in mice.

Abstract
In this study, we evaluated the immunogenicity and protective efficacy of a candidate attenuated H5N1 pre-pandemic influenza vaccine of clade 2.3.4, rgAnhui, which was reverse genetically generated from highly virulent A/Anhui/01/2005 (H5N1) wild-type virus. When a low-dose antigen (0.3μg HA) vaccine was combined with aluminum hydroxide adjuvant, virus neutralization and anti-HA IgG antibodies induced in the sera of vaccinated mice showed similar levels as those in mice vaccinated with non-adjuvanted high-dose antigen (3μg HA) vaccine. Serum antibodies had broad reactivity against highly pathogenic H5N1 viruses of both homologous and heterologous clades. All mice vaccinated with adjuvanted and non-adjuvanted rgAnhui vaccines at low and high antigen doses survived, without any significant weight loss, lethal challenge infection with homologous clade 2.3.4 viruses, including antigenic variant virus and heterologous clade 2.1.3. Mice vaccinated with low-dose antigen without adjuvant, however, exhibited 20% and 60% survival rates against clade 1 and clade 2.2 viruses, respectively; but, addition of adjuvant improved these rates to 80% and 100%, respectively. The data strongly suggest that aluminum hydroxide-adjuvanted rgAnhui vaccine can elicit broad cross-reactive and protective immunities against homologous and heterologous clades, and that the rgAnhui vaccine is a useful pre-pandemic H5N1 vaccine.
AuthorsYuichi Harada, Ai Ninomiya-Mori, Yoshimasa Takahashi, Masayuki Shirakura, Noriko Kishida, Tsutomu Kageyama, Yoshikazu Tada, Masato Tashiro, Takato Odagiri
JournalVaccine (Vaccine) Vol. 29 Issue 46 Pg. 8330-7 (Oct 26 2011) ISSN: 1873-2518 [Electronic] Netherlands
PMID21911027 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Ltd. All rights reserved.
Chemical References
  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
  • Influenza Vaccines
  • Vaccines, Synthetic
  • Aluminum Hydroxide
Topics
  • Adjuvants, Immunologic (administration & dosage)
  • Aluminum Hydroxide (administration & dosage)
  • Animals
  • Antibodies, Neutralizing (blood)
  • Antibodies, Viral (blood)
  • Body Weight
  • Cross Protection
  • Cross Reactions
  • Female
  • Immunoglobulin G (blood)
  • Influenza A Virus, H5N1 Subtype (classification, genetics, immunology)
  • Influenza Vaccines (administration & dosage, immunology)
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections (mortality, pathology, prevention & control)
  • Survival Analysis
  • Vaccines, Synthetic (administration & dosage, immunology)

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