Technically Speaking: essential elements

Independent project group develops guidelines for coccidiosis vaccines

By H.D. Chapman, Ph.D. Department of Poultry Science, University of Arkansas, USA

Increased recognition that live vaccines provide a valuable alternative to chemotherapy for coccidiosis control has encouraged researchers around the world to consider development of coccidiosis vaccines for local use. As with all products developed for the poultry industry, it is essential that vaccine development be carried out using rigorous procedures and high professional standards that also comply with any official regulations that may be applicable.

Guidelines have long been available to help researchers satisfy standards for drugs and many viral and bacterial vaccines — but none have been produced for vaccines against coccidiosis. Consequently, the author recently assembled a group of experts to participate in a joint project aimed at finding a remedy to this deficiency. The team included myself and the following esteemed experts:

• Professor Martin Shirley, deputy director of the Institute for Animal Health, United Kingdom, lead the research team in the 1980s that developed the world’s first attenuated coccidiosis vaccine. More recently, he was instrumental in organizing a successful project to sequence the entire genome of Eimeria tenella, the most widespread, pathogenic species of Eimeria that infects the chicken.

• Dr. Ray Williams, of the UK, is one of the world’s leading coccidiosis researchers with vast experience in the poultry industry. Dr. Williams has published numerous papers about avian coccidiosis and vaccination.

• Dr. Brian Roberts, also of the UK, is an international authority with detailed knowledge of the registration requirements necessary for obtaining marketing authorization for poultry vaccines.

The project group’s goal was to develop guidelines to assist scientists and others in the design, implementation and interpretation of studies for assessing the efficacy and safety of live coccidiosis vaccines and to suggest standards for manufacture and quality control. The resulting guidelines are intended to help researchers obtain specific information for those involved in the decision making process and to facilitate the worldwide adoption of consistent, standard procedures.

The team received advice from veterinarians, researchers and those with practical knowledge of poultry production. Scientists working in government, academia and industry around the world were consulted, but the sometimes controversial opinions expressed in the guidelines are the group’s own. A leading poultry veterinary journal, Avian Pathology, published the guidelines1, which are shown on the following page.

Procedures

Birds in vaccine development studies should be vaccinated under conditions that duplicate as closely as possible the manner in which vaccination will be carried out in the field. Subsequently, birds should be intentionally challenged with the parasite to see whether they have acquired protective immunity.

An important aspect of experimental design is that vaccinated birds must be reared in floor-pens to allow adequate exposure to infection following vaccination; the challenge phase of experiments can be carried out in wirefloored cages or pens. The guidelines as published in Avian Pathology provide detailed information about conducting these studies.

Once satisfactory results have been obtained from experimental studies, large-scale field tests can then be carried out; this is important to establish that a vaccine is safe for use in the field. Preferably, such trials should be carried out in all geographical regions where a vaccine is intended for use.

Criteria for efficacy

The criteria conventionally used to evaluate drug efficacy, such as weight gain, mortality, feed conversion and the presence of intestinal lesions, may similarly be used to determine the extent of immunity development following vaccination and subsequent challenge. However, in the opinion of the project group, lesion scores are of questionable value. Lesion scoring requires considerable expertise. It is inherently subjective and, unfortunately, does not necessarily correlate with protection because lesions may be present in the gut of partially or completely immune birds, even though their weight gain is not depressed.

In some countries, guidelines for avian vaccines have been produced by registration authorities, but specific standards for anticoccidial vaccines in poultry apparently have not been published so far. Detailed knowledge of any local requirements is essential to obtain product approval.

The guidelines drafted by the project group provide information on the general requirements of regulatory authorities based on regulations currently applicable in the EU and the US. Topics covered in the guidelines include efficacy requirements, safety and environmental considerations, quality control in terms of purity, pharmacopoeial sterility, potency, quantification and stability etc., manufacturing practice and, last but not least, necessary documentation.

Guidelines for coccidiosis vaccines Good biosecurity helps ensure that coccidiosis vaccines are free from contaminants. Ideally, any live anticoccidial vaccine should have the following 13 characteristics: Induce protective immunity against economically important species of Eimeria Be safe for the target host, non-target animals and humans Not represent an environmental hazard Comprise parasites of normal or low virulence Comprise parasites that remain viable during storage for a reasonable period of time Protect against field strains in geographical areas where the vaccine is used Be administered by a commercially practical method to ensure that as many birds as possible receive an immunizing dose Have no adverse effects on final performance or other production criteria Be compatible with other poultry vaccines Be free from viral, bacterial, mycoplasmal, fungal and chemical contaminants Be cost effective compared with other methods of coccidiosis control Include drug-sensitive lines that may reduce drug resistance in field populations Raise no problems with residues or impose a need for mandatory withdrawal periods

Purpose

In the foreseeable future, new vaccines are likely to be introduced for protecting poultry against coccidiosis. Some of these vaccines will be produced by companies with an established track record in providing high quality vaccines to the poultry industry but, as pointed out at the 2005 International Coccidiosis Conference held in Brazil, many smaller companies lacking such experience are also likely to be involved. It is important that all commercial vaccines, whatever their source, be produced to the same high standards. For example, in the US, source flocks used to produce poultry vaccines must be serologically tested to ensure freedom from at least 11 kinds of virus, not to mention Mycoplasma and Salmonella species.

To reiterate, the purpose of the project group’s guidelines is to facilitate the worldwide adoption of consistent, standard procedures for evaluating the efficacy, safety, manufacture and quality control of coccidiosis vaccines for poultry. The poultry industry deserves no less.

Reference

¹ Chapman, HD, Shirley, MW, Williams, RB. Guidelines for evaluating the efficacy and safety of live anticoccidial vaccines, and obtaining approval for their use in chickens and turkeys. Avian Pathology 2005;34: 279-290.

Source: CocciForum Issue No.12, Schering-Plough Animal Health.