Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 10/1/2006
Publication Date: 10/19/2006
Citation: Swayne, D.E. 2006. Avian Influenza vaccine technologies and laboratory methods for assessing protection [abstract]. In: Working Document, Requirements for Production and Control of Avian Influenza Vaccines, European Directorate for the Quality of Medicines, Strasbourg, France, October 19-20, 2006. p. 23. Interpretive Summary:
Technical Abstract: Vaccines can be used in avian influenza (AI) control programs to prevent, manage or eradicate AI from poultry and other birds. The best protection is produced from the humoral response against the hemagglutinin (HA) protein and such protection is HA subtype specific. A variety of vaccines have been developed and tested under experimental conditions with a few receiving licensure and field use following demonstration of purity, safety, efficacy and potency. Vaccines technologies for AI vaccines are categorized into four groups: 1) inactivated whole AI viruses, 2) in vitro expressed HA protein, 3) in vivo expressed HA protein, and 4) naked nucleic acids (primarily cDNA). Categories 1, 2, and 4 require parenteral administration of the vaccines while category 3 vaccines have administration routes of either parenteral, direct respiratory or in ovo. The in vitro expressed HA protein vaccines include eukaryotic tissue cultures, plants, yeast, bacteria and viruses. The in vivo expressed HA protein vaccines are predominately avian viruses (fowl poxvirus, herpesvirus of turkeys, infectious laryngotracheitis virus, adenovirus, paramyxovirus type 1 and influenzavirus A) but also some bacterial vectors such as salmonella have been tested. Current licensed vaccines are predominate inactivated whole AI vaccines. Typically these vaccines are composed of a low pathogenicity (LP) AI virus strain (obtained from a field outbreak), grown in embryonating chicken eggs, chemically inactivated and emulsified in an oil adjuvant system. Occasionally, high pathogenicity (HP) AI strains have been used, but they require high biocontainment facilities for safe manufacturing. Recently, reverse genetic procedures have been developed that allow construction of vaccine strains using a genetically altered HA (changing HP HA proteolytic cleavage site to LP) and a backbone of internal gene segments for safe, high growth production. Other licensed AI vaccines include recombinant fowl poxvirus vector with an AI H5 insert and a recombinant Newcastle disease virus vector with an AI H5 gene insert. The latter vaccine can be mass administered via aerosol application. One of the greatest challenges of AI vaccines is laboratory assessment of vaccine protection. Direct measurement of protection can include: 1) assessment of prevention of morbidity and mortality, 2) reduction in challenge virus replication in respiratory and gastrointestinal tracts, and 3) prevention of challenge virus transmission through contact exposure. Indirectly, protection can be assessed by serological response that correlates with protection such as virus neutralizing or hemagglutination inhibition titers. For parenteral vaccines several important factors impact the protective response and should be part of the assessment; i.e. amount of antigen, type of adjuvant, site of injection, and genetic relatedness of HA protein between vaccine and circulating field strain.