Submitted to: Options for the Control of Influenza Conference
Publication Type: Abstract Only
Publication Acceptance Date: 4/1/2007
Publication Date: 6/17/2007
Citation: Matsuoka, Y., Achenbach, J., Swayne, D.E., Klimov, H., Donis, R. 2007. Cross-protective efficacy of reverse-genetics-based H5N1/PR8 reassortant vaccines against challenge infection with homologous and heterologous clade viruses in mice [abstract]. In: Abstracts of Conference for Options for the Control of Influenza VI, June 17-23, 2007, Toronto, Canada. p. 301.
Technical Abstract: Since 2003, highly pathogenic H5N1 influenza A viruses have caused outbreaks in poultry which resulted in confirmed human infections in 11 countries. There is concern that H5N1 may cause a pandemic if it acquired the ability to transmit among humans. A major component of preparedness plans to mitigate the impact of an H5N1 pandemic is vaccination. CDC has developed several reverse genetics-derived pre-pandemic vaccine candidate viruses. H5N1 influenza viruses isolated during the past three years are categorized into several different clades based on genetic and antigenic characteristics of the hemagglutinin (HA) gene. Most currently circulating H5N1 viruses belong to clade 2 and this group of viruses are further divided into subclades. Pandemic vaccines we developed include strains from the most highly prevalent clades in poultry that were also causing human infections. As countries prepare for a possible H5N1 pandemic by stockpiling vaccine, the choice of appropriate vaccine strain becomes paramount. To inform this selection, we analyzed the protective efficacy of vaccines from each of the clades against infection with viruses from a heterologous clade. Reassortant viruses containing attenuated HA and intact neuraminidase (NA) genes from A/Vietnam/1203/04 (clade 1), A/Vietnam/Hanoi30408/04 (clade 1) and A/Indonesia/05/05 (clade 2) and 6 internal genes from A/Puerto Rico/8/34 (PR8) viruses were produced and designated as VN1203/PR8, VN30408/PR8 and Indo05/PR8, respectively. Mice were immunized with 10 microgram of each formalin-inactivated vaccine with or without Alum twice two weeks apart and were challenged with two clade 1 viruses at 4 weeks after the second immunization. All mice immunized with reassortant vaccines were completely protected from lethal challenge infection. Immunized mice showed no sign of illness and all survived. Hemagglutination inhibition (HI) titers in sera from immunized mice revealed protective level of HI antibody (>40HI) against the homologous vaccine strain but not the heterologous strain after the second immunization. Preliminary results from microneutralization test showed a similar pattern of antibody reactivity. The results indicate that mice vaccinated with inactivated H5N1 vaccine against one clade develop cross-protective immune responses against different clade.