Vector vaccines come of age

A new generation of genetically-engineered vector vaccines has the potential to supplement and eventually replace existing modified live-virus products.

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Attendees at the 42nd National Meeting on Poultry Health and Processing were provided with an update on genetically engineered vector vaccines. Dr. David Shapiro, director of veterinary services for Perdue Farms, described the current USDA-licensed HVT vector vaccines and their field application. Professor Robin W. Morgan of the Delaware Biotechnology Institute, University of Delaware, described experiments to evaluate the efficacy of recombinant vector vaccines to stimulate immunity against infectious bursal disease (IBD) and Newcastle disease (ND). These complementary presentations confirmed the technical acceptability of the new generation of vaccines which have the potential to supplement and eventually replace existing modified live virus products.

HVT Vector Vaccines

The herpesvirus of turkeys (HVT) has been selected as a vector for a number of antigens based on inherent advantages offered by the agent. As a fairly large virus, HVT can accommodate a number of inserts. Since HVT can be administered either in-ovo or as a hatchery subcutaneous vaccine, the target antigen can be administered safely using existing technology. As HVT continues to replicate in the host, the "cargo" antigen is continually expressed and stimulates an immune response. It is accepted that since HVT vectors express only selected antigenic components of the target pathogen, the safety of vector vaccines is obviously at a higher level compared to conventional modified live vaccines including larynogotracheitis and infectious bursal disease.

The greatest disadvantage associated with the new generation of vaccines relates to cost. Manufacturers have expended considerable resources on selecting vectors, establishing constructs, and on exhaustive testing for efficacy and safety required for registration. This commitment is reflected in price as manufacturers are obliged to amortize research-and-development costs over a limited time period dictated by competition, innovation and patent protection. It is possible that recombinant vector vaccines may have narrower immunogenicity than conventional modified live virus vaccines, although initial field trials and laboratory studies have confirmed protection against target pathogens.

Disputes over the ownership of intellectual property which emerged in the early 1990s impeded the commercialization of vector vaccines. Despite patent protection, it is relatively easy to copy and produce a vector vaccine. This is a significant problem in international marketing where certain countries do not protect developers of innovative products or respect patent rights. (See Commercialization Of Vector Vaccines, page 40.)

Recombinant IBD And ND Vaccines

Controlled studies on HVT vector vaccines conducted at the University of Delaware, in association with AviServe LLC operated by Prof. John Rosenberger, were described by Dr. Robin Morgan. Exposure trials were conducted in colony test houses using small groups of commercial broiler chicks. Solid protection against Marek's disease was determined using a virulent challenge strain. Concurrently, the respective ability of HVT vector vaccines to provide protection against IBD and ND was also quantified. The trials incorporated placement of "shedder" chicks inoculated with MD virus to simulate field conditions. The protection provided against either IBD or ND was also assessed in the presence of a virulent MD challenge administered directly to chicks previously vaccinated with the recombinant products. Protection against IBDV was assessed by measuring bursal-to-body weight ratio after challenge at five weeks of age. Attempts at re-isolation of LaSota strain NDV from tracheas represented the criterion of protection against NDV in chicks vaccinated with the recombinant HVT-ND vaccine.

The Delaware team demonstrated impressive protection against MD using the range of commercial vaccines licensed to protect against either MD/ND or MD/IBD. The ND-IBD products supported acceptable bursal-to-body weight ratios although superimposing MD challenge decreased the efficacy of protection. The recombinant HVT-ND product did not prevent subsequent multiplication of a challenge ND virus in the trachea of vaccinated broilers. The rate of re-isolation of the ND challenge virus was increased when chicks were subjected to virulent MD infection. Although vaccinated flocks are apparently protected against ND, there are obvious epidemiologic implications relating to shedding which maybe significant in the context of a vvND outbreak.

The trials conducted by the Delaware consortium involved administration of complete doses of the HVT vector vaccines. Under field conditions, U.S. integrators dilute conventional vaccines to reduce cost, with, in most cases, minimal impact on effectiveness. It was suggested that subsequent trials, especially evaluating HVT-vectored ILT vaccines, should consider reduced doses in an attempt to ascertain cost effectiveness rather than the technical attributes of the new range of vaccines.

Factors Surrounding Adoption

Dr. Shaprio emphasized that evaluation of recombinant vaccines will depend on a number of factors including conventional parameters of performance comprising energy conversion, livability and weight for age but also plant characteristics including quality and yield. Bottom-line evaluation will obviously take into account the actual cost of vaccines in relation to possible improvements in performance. Adoption of recombinant vaccines will be determined by cost effectiveness over the long term. It is accepted that the current range of modified live vaccines will not undergo any appreciable improvement, and the inherent problems of emerging variants, specifically, IBD and ILT, clinical infections will dictate alternative approaches to suppressing disease in our industry. Genetically-engineered vaccines will not achieve commercial acceptance on the basis of innovation and novelty. They will obviously have to earn their spurs based on protection, performance and financial return. It is recognized that the current USDA licensing process is a deterrent to rapid development and testing of vaccines. Deficiencies, which are noted under limited field trials which were not apparent in the laboratory, will require modification of the constructs. Current procedures require a protracted series of re-submissions. A more flexible approach will be required from USDA to expedite development and licensing of vaccines and ultimately enhance efficiency in the industry.

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