Vaccinology of PRRS

Abstract - Vaccinology is the study of vaccine development, testing, application, and use under field conditions. Because application and use under field conditions are extensively covered in other presentations, this paper will be limited to the development of Porcine Reproductive and Respiratory Syndrome (PRRS) vaccines. PRRS is a disease that seems more difficult to fight than was originally expected. This is partly due to the fact that the PRRS virus (PRRSV) can infect macrophages and circumvent immune barriers like neutralising antibodies. Although the genome is known, the biology of the virus and pathogenesis are only partially known. Now that the genome can be manipulated as full length DNA copies of the original PRRSV RNA genome, we can study the ways in which the virus may survive in the host and can maintain its presence despite the immune response of the pig. The immunity in reconvalescent animals is protective, meaning that it prevents the virus from inducing disease symptoms. But it may not prevent PRRSV from entering the lung alveolar macrophages of the host. Antibodies against PRRSV may even help the virus to enter macrophages by antibody dependent enhancement of phagocytosis. It is more likely that immunity protects at another level, for instance by preventing viremia. During viremia, the virus floods the body and replicates in all susceptible cells it encounters. In this way, macrophages in the lymphnodes, spleen, bone marrow, and fetuses may become infected. In order to develop a vaccine against PRRS, knowledge of the pathogenesis is important to select the kind of immune response: local immunity in the lung or systemic immunity, or a combination of both. Since the first occurrence of PRRS, many different PRRS vaccines have been produced and tested under controlled laboratory conditions and in field trials. The very first vaccines consisted of inactivated viruses. These vaccines were non-protective against PRRSV infection as quantified by the decrease of the length and duration of viremia. Subunit vaccines were also constructed, consisting of Open Reading Frames (ORFs) incorporated into baculovirus to produce the protein in vitro, or into pseudorabies virus as a vector vaccine. The baculo ORF7 product (viral nucleoprotein) induced antibodies in pigs upon vaccination, but did not provide immunity against a field virus challenge. ORFs 2, 3, 4, and 5, incorporated into pseudorabies as a vector vaccine, did not induce an antibody response in vaccinated animals. Since then, attenuated vaccines have been provisionally regarded as the vaccine of choice and they have surely helped in controlling PRRS outbreaks in the field. Recently, more sophisticated vaccines, such as the DNA vaccine, appear to induce protective immunity in pigs, predominantly by induction of cellular immunity. The question remains as to whether DNA integration in the genome of food animal cells will be accepted by consumer organisations and authorities. All these different vaccines have to be evaluated for efficacy and also some for safety. There is an obvious need for standardised animal models for efficacy studies. PRRS related symptoms vary according to the age and status of the animals. In young piglets, respiratory distress is most prominent. In fattening pigs, respiratory problems are often more diffuse and complicated by concomitant respiratory pathogens, resulting in decreased weight gain. In pregnant sows, reproductive disorders are prominent at the end of the gestation period and in the offspring during the suckling period. Which animal model will produce the best results is difficult to say and depends on the vaccine claims. When a vaccine is claimed to protect against respiratory problems, the best model to show efficacy will be the vaccination and challenge of young pigs and test for viremia, clinical respiratory distress, and weight gain. The sow model is only used as a safety model, inoculating the vaccine in the third period of gestation. When a vaccine is claimed to protect against reproductive problems, a pregnant sow protection model (vaccination/challenge) will be necessary in addition to the sow safety model. Sow studies are expensive and difficult to manage, which has led to a number of studies being performed with a subminimal number of animals. Statistical analysis of the results and comparison of test results cannot be properly performed if the minimal requirements are not met regarding group size, gilt selection, health status, and the inclusion of control groups. The same is true for animal studies that examine respiratory diseases. Vaccine efficacy and safety are the key parameters for any vaccine, and in particular for PRRS vaccines. A standardised, globally accepted animal model used by PRRS researchers to evaluate vaccine candidates would facilitate the comparison of test results in a more balanced way, and would in the end save a lot of animal lives. Efficacy of PRRS vaccines cannot be expected to surmount the immunity after field virus infection which lasts for about 18 months. This means that repeated applications of the vaccine will be necessary to control the field situation in pig dense areas. The safety of non-transmittable, genome-stable viruses or of incomplete viruses will be a major issue in these conditions. The balance between efficacy and safety will eventually dictate which vaccines will be used.