Vaccine, Diagnostic Test Development and Immunology Aspects of Avian Influenza
Avian influenza is a zoonotic disease and is seen as one of the most important emerging diseases with serious economic consequences. Although some vaccines for poultry are available, all vaccines have considerable drawbacks with regard to dose and application methods (injection), onset of immunity, efficacy or costs of production and application which limit their use.
The primary aim of this project is to develop better avian influenza vaccines through live or vector vaccines that could be mass applicable through spray, drinking water or eye drop. These vector vaccines would offer considerable advantages - mass applicable, less labour intensive and animal friendly application, protection by local and systemic immunity and less interference with eventual maternal antibodies, more complete protection through cellular and humoral immunity, faster onset of immunity when used in face of an outbreak and cheaper production methods.
The project exploits recently acquired knowledge concerning the molecular characterisation of the viruses resulting in the construction of candidate strains with highly interesting efficacy and safety profile. Safety and efficacy with Newcastle disease (NDV) vectors and infectious laryngotracheitis (ILT) vectors both for H5 and for H7 inserts have already been demonstrated in vivo.
A system in which gene cassettes for the foreign proteins can easily be constructed and exchanged will be developed and will be able to respond very quickly to a change in antigenicity of the field virus. Further optimised additional candidate strains will be constructed and extensively tested. Experiments on genetic in vitro and in vivo stability, immunological responses, virulence testing, spreading, and transmission studies in chickens, ducks and other avian species will be performed.
The vaccines to be developed would also have marker aspects which will allow the differentiation of infected from vaccinated animals (DIVA principle). The development of sensitive, specific and easy to use marker diagnostic tests that will be compatible with the vaccines is another goal of this project.[+] Read More
The highly pathogenic H5N1 avian influenza (AI) currently circulating in Asia, and recently in northern and western Africa and Europe, has led to the deaths of more than 150 million birds and over 150 humans. Due to the seriousness of this threat, some countries are taking steps to vaccinate their entire poultry population. Currently, a consensus is emerging that vaccination of birds at risk could be a critical part of a control strategy in averting a human pandemic.
Although very useful in the fight against avian influenza, all currently available influenza vaccines have considerable shortcomings; several vaccines developed over the past two decades to protect poultry against the highly pathogenic H5 or H7 are based on inactivated whole virus vaccines. Apart from the challenge of setting up a robust diagnostic test for differentiating vaccinated from infected animals, these vaccines have to be administered by labour intensive and expensive parenteral injections.
In view of the worrying spread of epidemic avian influenza H5N1 and the large undertaking to vaccinate billions of birds in some parts of the world, development of efficacious vaccines that could be administered by mass application routes, such as spray or drinking water, is urgently needed. In the endeavour to develop improved vaccine against AI, recombinant DNA technology was employed to generate vectored, subunit or DNA vaccines. Although a wide range of these vaccines has been experimentally shown to be effective against AI, only a fowl pox-vectored vaccine with H5 gene insert is commercially available. This recombinant vaccine, however, also requires administration by parenteral injection.
In order to better control avian influenza, more effective mass applicable vaccines are needed. For better design of future vaccines and strategies to combat avian influenza more insight is also required into the immunological mechanisms and characterisation of immune responses after vaccination and infection.
An easy to use, sensitive and specific serological test allowing the DIVA principle, which can be used in conjunction with the use of inactivated or vectored vaccines, is needed.
An ideal vaccine to be added in controlling AI should be: i) efficacious in reducing virus transmission; ii) genetically close to the circulating virus; iii) serologically distinguishable from wild type virus; iv) applicable by mass administration routes; and v) inexpensive.
Recent achievements showed that safe and efficacious NDV vectors could be constructed that would make development of a vaccine with the above characteristics possible. NDV vectors carrying H7 respectively H5 gene inserts were recently constructed and 100% protection against clinical disease as well as considerable reduction in virus shedding was observed after challenge with NDV and AI. However, the H7 and H5 ORF used for the construction of these vectors was not derived from recent isolates and it can be expected that protection will be enhanced when using vector vaccines carrying recent H5 or H7 genes. This knowledge will be used to construct optimised NDV vector vaccines that will have advantages in terms of their improved efficacy against recent H5N1 isolates. The NDV parent strains that will be used for the construction of the recombinants are a vaccine strain that is widely used in the field for years and with a well established safety record.
Objectives of the vector vaccines constructed in the project:
This project is expected to deliver the first mass applicable live vaccine against highly pathogenic H5N1 avian influenza. The vaccine would offer major technical advantages, including production aspects, over the currently existing vaccines.
An easy to use, sensitive and specific serological test allowing the DIVA principle, which can be used in conjunction with the use of inactivated or vectored vaccines, will considerably enhance optimal avian influenza vaccination and control strategies.
Better knowledge of the critical pathways involved in influenza immunity and immunopathology may eventually contribute to improved vaccine design, and optimised immunisation or other intervention strategies.
The development of molecular biological tools will allow in the future a quicker response to changes in antigenicity of the field-virus. The construction of gene cassettes that will allow fast integration of the H region of future genetically and antigenically different influenza strains in the ND vector will allow a much faster response for construction of updated vaccine strains.
Live vaccines with much easier methods of application will result in less labour and thus lower costs of vaccination. Methods of application via natural route (drinking water, spray, eye drops) are easier to perform and in certain areas could offer considerable advantages over parenteral vaccination. Less costly and easier vaccination methods will also increase compliance with vaccination campaigns and policies, especially in developing countries.
Vaccination by more natural application routes will also result in a much more animal friendly procedure, as stress due to vaccination will be considerably reduced and animal welfare greatly improved. The project will also deliver fast, sensitive, robust and specific ELISA tests. This will enable the DIVA concept. These tests can be used in conjunction with the newly developed vaccines or with existing vaccines.
The availability of easy to perform, fast and reliable test systems that could be used for mass-testing is a prerequisite for the development and successful implementation of control measures and eradication policies.
The successful use of the live vaccine and DIVA tests will offer major possibilities and tools in the fight against avian influenza and thus will have a major contribution to economical poultry farming and human health.