Ceva Animal Health organized the Vector Vaccines Symposium, which took place from October 6-8 in San Diego, Calif. The symposium, which attracted over 300 attendees, included presentations by Ceva’s scientists in addition to U.S. and EU research workers affiliated to universities and veterinarians involved in poultry health.
Advantages of vector vaccines
Live attenuated viral vaccines have served as the mainstay of disease prevention in the poultry industry for the past 50 years. Problems associated with undesirable post-vaccination reactions, extensive spread of vaccine strains such as chick embryo-origin ILT in the U.S. broiler industry, emergence of IBD variants as well as the remote possibility of reversion are significant issues with this class of vaccines. The strategy of using mild live vaccines to prime the immune system followed by less attenuated live vaccines and then administration of inactivated emulsions vaccines is generally adopted by egg and chick producers for rearing long-lived flocks. The use of inactivated vaccines in parent stock can give rise to tolerance and attaining a satisfactory level of acquired immunity in young progeny is an ongoing problem due to maternal body interference.
During the 1970s, advanced in biotechnology gave rise to a new class of vaccines. Sequences of DNA, coding for immunogenic antigens associated with specific pathogens were incorporated into the genome of non-pathogenic viruses. Administration of the modified vector vaccine induces immunity without the obvious disadvantages associated with traditional live attenuated products.
The first pox virus-vectored vaccines proved highly effective against Newcastle disease and avian influenza when administered to specific pathogen-free chicks. Unfortunately, in some situations maternal antibody against some of the inserts or the vector inhibited durable protection under field conditions. Notwithstanding this problem, successful results have been obtained in Mexico controlling avian influenza and Newcastle disease with appropriate modifications to parent vaccination programs.
Dr. Robert Webster of St. Jude’s Hospital, a world renowned expert on human influenza, emphasized the need to adapt vector technology to controlling influenza in human populations. Reliance on embryonated eggs to propagate influenza vaccines for humans is costly and is associated with risks of inducing sensitivity reactions in vaccine recipients. He stressed that effective control of avian influenza in poultry populations is essential in preventing the emergence of new strains which may be pathogenic to human populations.
The reluctance of regulatory authorities to accept this new technology when originally presented for licensing inhibited commercialization and adoption of vector vaccines. Dr. Kristi Moore, the vice president of research and development at Ceva-Biomune USA, indicated that the Center for Veterinary Biologics has classified genetically modified products into three categories. These include:
- DNA subunit vaccines,
- gene deleted vaccines and
- vector vaccines.
At the present time, only HVT and pox are used as vectors, but it is possible that other viral and bacterial candidates may be selected. Requirements for registration of vector vaccines include safety, efficacy equivalent to or superior to current conventional products, absence of reversion under field conditions, and non-spreading between vaccinated and non-vaccinated contacts. Vector vaccines have been shown to stimulate both cellular and humoral immunity.
A major advantage of vector vaccines is the ability to implement the DIVA Principle which can be used to differentiate infected from vaccinated subjects. This is critical in diagnosing the presence of an infection in a population or area and to certify that populations which have been vaccinated and demonstrate antibody are in fact free of infection.
Dr. Thierry van den Berg, director of the Veterinary and Agrichemical Research Center in Belgium, reviewed experiments to control Newcastle disease (ND). The most efficient program involved administration of HVT-vectored vaccine at 18 days of incubation by in ovo injection followed by administration of a lentogenic live attenuated ND product adjuvanted with chitosan using the aerosol route at the hatchery. This program was more effective than using either HVT-vectored ND alone or relying only on live ND vaccine in the face of high challenge under experimental conditions.
There are differences among vaccine constructs as demonstrated by Dr. Jack Rosenberger using two different HVT-ND vector vaccines against ND challenge, reflecting conditions in the Delmarva area. Substituting live attenuated ND vaccine with an HVT-ND vectored vaccine improved the field performance of broilers, according to Dr. Tom Holder. Part of the benefit was attributed to the fact that the deleterious effect from a combination ND-IB (infectious bronchitis) vaccine was eliminated.
It is well documented that there is mutual interference when administering combination live attenuated ND-IB vaccines, resulting in subsequent susceptibility to infectious bronchitis. Since in ovo vaccination is an established practice in the broiler industry in the U.S., incorporation of vector vaccines based on HVT is perfectly acceptable and imposes no departure from existing practices in an intensively conservative and price-conscious industry.
An HVT vectored infectious bursal disease (IBD) vaccine was used by Dr. Gregg Cutler to control the only documented outbreak of very virulent IBD in the U.S. Initially, an intermediate plus IBD vaccine was used on an off-label basis to control the clinical outbreak and to limit spread. Thereafter D78 strain vaccine was administered with transition to HVT-IBD vaccine in conjunction with intermediate D78 strain. The combination of vaccines effectively eradicated infection.
Dr. Carlos Barranon of PATSA, a broiler integrator in Mexico, described the successful use of a pox/ILT product to control laryngotracheitis (ILT) in flocks. The pox-vectored ILT vaccine effective eliminated field virus and was more successful than either tissue culture or chick embryo origin live attenuated LT vaccines. It is noted that virtually all ILT clinical outbreaks among broilers in the U.S. can be ascribed to CEO live attenuated chick embryo origin ILT vaccines which have undergone field reversion.
Dr. Jagdev Sharma, the originator of in ovo vaccination using HVT, commented on the safety and efficacy of HVT-vectored vaccines. Insertion of genes to stimulate immunity against ND, ILT and AI have not altered the protective efficacy of HVT or resulted in any detectable clinical changes in recipient flocks.
An important development to reduce cost and generate greater efficiency would be combining antigens creating multivalent products. An HVT or other suitable vector that could stimulate immunity against ND, ILT and IBD or a combination of these diseases would be a “killer app” and would certainly further stimulate the adoption of in ovo or sub-cutaneous administration at the hatchery to control broiler diseases worldwide.
Challenges facing the development and commercialization of vaccines employing vector technology will include selection of vectors and insertion of appropriate genetic codes to stimulate antibody against target infections. Collection of data on efficacy and safety is expensive but required by regulatory authorities, who are now more familiar with this emerging technology. Questions concerning duration of immunity have yet to be resolved especially in egg-production and breeder flocks. The second issue is how vector vaccines will be incorporated into existing programs using both live attenuated viral vaccines and inactivated emulsion products.
Cost is a significant consideration as many of the biologics companies have been forced to amortize research and development costs over a limited volume of vaccines. Claims relating to intellectual property and conflicting patents have impeded progress in adoption of vector vaccines although many of the difficulties which arose during the ’90s have now been addressed. The current round of consolidations and acquisitions among pharmaceutical companies involving their livestock biologics subsidiaries has the potential to expedite the future adoption of vector vaccines.
Ceva Animal Health is complimented on its foresight in arranging the symposium and its commitment to refining and commercializing vector technology that will ultimately benefit the entire industry and all consumers of poultry products.