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      Role of vaccination-induced immunity and antigenic distance in the transmission dynamics of highly pathogenic avian influenza H5N1

      , , , , ,
      Journal of The Royal Society Interface
      The Royal Society

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          Abstract

          <p class="first" id="d9244108e207">Highly pathogenic avian influenza (HPAI) H5N1 epidemics in poultry cause huge economic losses as well as sporadic human morbidity and mortality. Vaccination in poultry has often been reported as being ineffective in preventing transmission and as a potential driving force in the selection of immune escape mutants. We conducted transmission experiments to evaluate the transmission dynamics of HPAI H5N1 strains in chickens vaccinated with high and low doses of immune escape mutants we have previously selected, and analysed the data using mathematical models. Remarkably, we demonstrate that the effect of antigenic distances between the vaccine and challenge strains used in this study is too small to influence the transmission dynamics of the strains used. This is because the effect of a sufficient vaccine dose on antibody levels against the challenge viruses is large enough to compensate for any decrease in antibody titres due to antigenic differences between vaccine and challenge strains. Our results show that at least under experimental conditions, vaccination will remain effective even after antigenic changes as may be caused by the initial selection in vaccinated birds. </p>

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          Most cited references44

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          Effect of vaccine use in the evolution of Mexican lineage H5N2 avian influenza virus.

          An outbreak of avian influenza (AI) caused by a low-pathogenic H5N2 type A influenza virus began in Mexico in 1993 and several highly pathogenic strains of the virus emerged in 1994-1995. The highly pathogenic virus has not been reported since 1996, but the low-pathogenic virus remains endemic in Mexico and has spread to two adjacent countries, Guatemala and El Salvador. Measures implemented to control the outbreak and eradicate the virus in Mexico have included a widespread vaccination program in effect since 1995. Because this is the first case of long-term use of AI vaccines in poultry, the Mexican lineage virus presented us with a unique opportunity to examine the evolution of type A influenza virus circulating in poultry populations where there was elevated herd immunity due to maternal and active immunity. We analyzed the coding sequence of the HA1 subunit and the NS gene of 52 Mexican lineage viruses that were isolated between 1993 and 2002. Phylogenetic analysis indicated the presence of multiple sublineages of Mexican lineage isolates at the time vaccine was introduced. Further, most of the viruses isolated after the introduction of vaccine belonged to sublineages separate from the vaccine's sublineage. Serologic analysis using hemagglutination inhibition and virus neutralization tests showed major antigenic differences among isolates belonging to the different sublineages. Vaccine protection studies further confirmed the in vitro serologic results indicating that commercial vaccine was not able to prevent virus shedding when chickens were challenged with antigenically different isolates. These findings indicate that multilineage antigenic drift, which has not been observed in AI virus, is occurring in the Mexican lineage AI viruses and the persistence of the virus in the field is likely aided by its large antigenic difference from the vaccine strain.
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            Emergence and predominance of an H5N1 influenza variant in China.

            The development of highly pathogenic avian H5N1 influenza viruses in poultry in Eurasia accompanied with the increase in human infection in 2006 suggests that the virus has not been effectively contained and that the pandemic threat persists. Updated virological and epidemiological findings from our market surveillance in southern China demonstrate that H5N1 influenza viruses continued to be panzootic in different types of poultry. Genetic and antigenic analyses revealed the emergence and predominance of a previously uncharacterized H5N1 virus sublineage (Fujian-like) in poultry since late 2005. Viruses from this sublineage gradually replaced those multiple regional distinct sublineages and caused recent human infection in China. These viruses have already transmitted to Hong Kong, Laos, Malaysia, and Thailand, resulting in a new transmission and outbreak wave in Southeast Asia. Serological studies suggest that H5N1 seroconversion in market poultry is low and that vaccination may have facilitated the selection of the Fujian-like sublineage. The predominance of this virus over a large geographical region within a short period directly challenges current disease control measures.
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              Impact of vaccines and vaccination on global control of avian influenza.

              There are 30 recorded epizootics of H5 or H7 high pathogenicity avian influenza (HPAI) from 1959 to early 2012. The largest of these epizootics, affecting more birds and countries than the other 29 epizootics combined, has been the H5N1 HPAI, which began in Guangdong China in 1996, and has killed or resulted in culling of over 250 million poultry and/or wild birds in 63 countries. Most countries have used stamping-out programs in poultry to eradicate H5N1 HPAI. However, 15 affected countries have utilized vaccination as a part of the control strategy. Greater than 113 billion doses were used from 2002 to 2010. Five countries have utilized nationwide routine vaccination programs, which account for 99% of vaccine used: 1) China (90.9%), 2) Egypt (4.6%), 3) Indonesia (2.3%), 4) Vietnam (1.4%), and 5) Hong Kong Special Administrative Region (< 0.01%). Mongolia, Kazakhstan, France, The Netherlands, Cote d'Ivoire, Sudan, North Korea, Israel, Russia, and Pakistan used < 1% of the avian influenza (AI) vaccine, and the AI vaccine was targeted to either preventive or emergency vaccination programs. Inactivated AI vaccines have accounted for 95.5% of vaccine used, and live recombinant virus vaccines have accounted for 4.5% of vaccine used. The latter are primarily recombinant Newcastle disease vectored vaccine with H5 influenza gene insert. China, Indonesia, Egypt, and Vietnam implemented vaccination after H5N1 HPAI became enzootic in domestic poultry. Bangladesh and eastern India have enzootic H5N1 HPAI and have not used vaccination in their control programs. Clinical disease and mortality have been prevented in chickens, human cases have been reduced, and rural livelihoods and food security have been maintained by using vaccines during HPAI outbreaks. However, field outbreaks have occurred in vaccinating countries, primarily because of inadequate coverage in the target species, but vaccine failures have occurred following antigenic drift in field viruses within China, Egypt, Indonesia, Hong Kong, and Vietnam. The primary strategy for HPAI and H5/H7 low pathogenicity notifiable avian influenza control will continue to be immediate eradication using a four-component strategy: 1) education, 2) biosecurity, 3) rapid diagnostics and surveillance, and 4) elimination of infected poultry. Under some circumstances, vaccination can be added as an additional tool within a wider control strategy when immediate eradication is not feasible, which will maintain livelihoods and food security, and control clinical disease until a primary strategy can be developed and implemented to achieve eradication.
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                Author and article information

                Journal
                Journal of The Royal Society Interface
                J. R. Soc. Interface
                The Royal Society
                1742-5689
                1742-5662
                January 13 2016
                January 2016
                January 13 2016
                January 2016
                : 13
                : 114
                : 20150976
                Article
                10.1098/rsif.2015.0976
                4759802
                26763336
                4de22043-e240-426f-a758-401077527e78
                © 2016
                History

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