Immunological basis of differences in disease resistance in the chicken

Genetic resistance to diseases is a multigenic trait governed mainly by the immune system and its interactions with many physiologic and environmental factors. In the adaptive immunity, T cell and B cell responses, the specific recognition of antigens and interactions between antigen presenting cells, T cells and B cells are crucial. It occurs through a network of mediator proteins such as the molecules of the major histocompatibility complex (MHC), T cell receptors, immunoglobulins and secreted proteins such as the cytokines and antibodies. The diversity of these proteins that mainly is due to an intrinsic polymorphism of the genes causes phenotypic variation in disease resistance. The well-known linkage of MHC polymorphism and Marek's disease resistance difference represents a classic model revealing immunological factors in resistance differences and diversity of mediator molecules. The molecular bases in any resistance variation to infectious pathogens are vaguely understood. This paper presents a review of the major immune mediators involved in resistance and susceptibility to infectious diseases and their functional mechanisms in the chicken. The genetic interaction of disease resistance with production traits and the environment is mentioned

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Vaccinology of PRRS

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

Chimeric arterivirus-like particles

The invention relates to the field for Arteriviruses and vaccines directed against infections caused by these viruses. The invention provides an Arteriviruses-like particle comprising at least a first structural protein derived from a first Arterivirus and a second structural protein wherein said second structural protein is at least partly not derived from said first Arterivirus

Comparative morphogenesis of three PRRS virus strains

The morphogenesis of a Dutch PRRS field strain virus (Lelystad virus) was studied and compared to that of a U.S. field strain VR2332 and its attenuated vaccine strain JJ1882. Porcine lung alveolar macrophages (PLAM) and CL2621 cells were infected with high doses of virus (MOI = 10). At 4, 6, 9, 12, 18, 24, and 48 h post infection (hpi) cells were fixed for electronmicroscopy or for detection of viral antigens by immunoperoxidase staining. From 6 hpi on, viral antigens were detected in the cytoplasm and from 9 hpi on completely assembled virus particles could be detected in infected cells. The three strains were similar in assembly of new virus particles, envelopment at the smooth endoplasmic reticulum, and egress from infected cells. However, distinct differences were seen in replication time of the three strains in various cell types. The Lelystad virus replicated very fast and efficiently in PLAM while VR2332 and JJ1882 replicated preferably in CL2621 cells. JJ1882 replicated faster in CL2621 cells than VR2332 did, probably because of increased adaptation to the cell-line. Although the U.S. and European strains differ at the level of the genome, morphogenesis is not visibly altered. There is however a distinct difference in preferred cell type between the European strain and the two U.S. strains

Linear hoof defects in sheep infected with foot-and-mouth disease

During the epidemic of foot-and-mouth disease (FMD) in the Netherlands in 2001, a sheep farm was identified that had been subclinically infected with the disease. The FMD virus genome was detected in 12 of 16 probang samples collected from the sheep and the virus was isolated from four of these samples. Linear defects were observed, 1 to 3 cm from the coronary band, in the hooves of several of the sheep. The defects were thought to have been caused by the FMD infection. It was thought that the distance of the defects from the coronary band might be an indication of the time since the animals had been infected. To determine the growth rate of the claws of sheep, the growth of the hoof horn of uninfected lambs and ewes was measured; in the lambs the growth rate was 0.44 mm per day and in the ewes it was 0.29 mm per da