Effect of maternally acquired Aujeszky's disease (pseudorabies) virus-specific antibody in pigs on establishment of latency and seroconversion to differential glycoproteins after low dose challenge

This study investigated whether (1) passively immune pigs could become latently infected after challenge with low doses of wild type pseudorabies virus (PRV) and (2) if seroconversion to PRV could be consistently detected using two commercially available differential diagnostic ELISAs. Three litters of piglets with passively acquired PRV serum neutralizing (SN) antibody (geometric mean titers 47.03 to 95.10) were challenged at 6 to 12 days of age with 236 to 500 TCID50 of Shope strain virus; pigs were vaccinated at 11 weeks of age with a commercially available genetically engineered vaccine (TK- gE- gG- Iowa S62 strain PRV). Vaccination was intended to reduce the risk of reactivation of latent infection resulting in spread of virulent PRV infection to previously uninfected pigs during the experiment. Vaccination at this age also approximated common field practices in infected herds. After 15 weeks, all challenged pigs were seropositive on the PRV glycoprotein (g or gp) E differential ELISA but were seronegative on the gG differential ELISA. All three challenge groups had pigs that were latently infected as evidenced by the detection of PRV DNA by polymerase chain reaction (PCR) assay of their trigeminal ganglia (TG). There was a significant inverse relationship observed for age at challenge and the proportion of PCR positive pigs in the group 15 weeks postchallenge (p = 0.0004). This trend was independent of the passively acquired PRV SN antibody titers at challenge. In this study, passively acquired antibody did not provide protection against establishment of latent infection in piglets after exposure to low doses of virulent PRV. These latent infections were detected serologically by only one of two available differential diagnostic ELISA.     

Prediction of microcirculatory oxygen transport by erythrocyte/hemoglobin solution mixtures

Vaccination with naked DNA may be an alternative to conventional vaccines because it combines the efficacy of attenuated vaccines with the biological safety of inactivated vaccines. We recently showed that the vaccination with naked DNA coding for the immunorelevant glycoprotein D (gD) of pseudorabies virus (PRV) induced both antibody and cell-mediated immunity in pigs and provided protection against challenge infection. To determine whether the efficacy of the naked DNA vaccination against PRV could be improved, we compared three sets of variables. First, the efficacy of the naked DNA vaccine coding only for the immunorelevant gD was compared with a cocktail vaccine containing additional plasmids coding for two other immunorelevant glycoproteins, gB and gC. Second, the intramuscular route of vaccination was compared with the intradermal route. Third, the commonly used needle method of inoculation was compared with the needleless Pigjet injector method. Five groups of five pigs were vaccinated three times at 4-weeks intervals and challenged with the virulent NIA-3 strain of PRV 6 weeks after the last vaccination. Results showed that although the cocktail vaccine induced stronger cell-mediated immune responses than the vaccine containing only gD plasmid, both vaccines protected pigs equally well against challenge infection. Intradermal inoculation with a needle induced significantly stronger antibody and cell-mediated immune responses and better protection against challenge infection than intramuscular inoculation. Our data show that the route of administering DNA vaccines in pigs is important for an optimal induction of protective immunity.     

Trypanosoma cruzi: protective response of vaccinated mice is mediated by CD8+ cells, prevents signs of polyclonal T lymphocyte activation, and allows restoration of a resting immune state after challenge

Currently, there is no vaccine available against Chagas' disease. Immune abnormalities induced by T. cruzi pose particular difficulties for vaccine development, since immunological memory must be able to overcome them to prevent spread of infection/sequelae. We have previously demonstrated that experimental vaccination with live CL-14 trypomastigotes does not induce polyclonal lymphocyte activation, immunosuppression, or pathology and efficiently immunizes against virulent T. cruzi. Herein we show that: (1) expansion of CD4+ and CD8+ subsets peaks 2 weeks after infective challenge in both challenged-vaccinated mice and infected controls, but the former exhibit a smaller increase in blastogenesis and in the numbers of activated CD11a(hi)CD4+ and CD11a(hi)CD8+ cells; (2) in long-term-vaccinated mice, expansion of activated subsets (CD62Llo/- and CD11a(hi)) is accelerated among CD8+ PBL 1 week after challenge; (3) challenged-vaccinated mice retract the CD8+-activated subset 5 weeks after challenge, different from infected controls; (4) protection conferred by CL-14 immunization can be adoptively transferred to na?ve recipients with lymphocyte suspensions, and prior depletion of CD8+ (but not of CD4+) cells abolishes protective immunity. Our findings indicate that protective immunity generated by CL-14 immunization involves a transient CD8+ recall response and is capable of preventing the signs of polyclonal lymphocyte activation induced by virulent challenge.     

Apoptosis induced in vivo during acute infection by porcine reproductive and respiratory syndrome virus

We studied apoptosis caused by porcine reproductive and respiratory syndrome virus (PRRSV) in vivo, focusing on the tissues that constitute the main targets for infection: lung and lymphoid tissues. Previous investigators have shown that the PRRSV glycoprotein p25, encoded by PRRSV open reading frame 5, induces apoptosis when expressed in COS-1 cells. Results of studies conducted in our laboratory indicate the simultaneous occurrence of PRRSV-induced alterations of spermatogenesis and apoptotic death of germinal epithelial cells in the testicle. In this study, the goal was to determine whether virus-induced apoptosis is a direct mechanism of cell death caused by PRRSV in infected pigs. Eight 3-week-old pigs were intranasally inoculated with PRRSV 16244B, a highly virulent field strain. Lung, tonsil, bronchial lymph node, spleen, and heart were assessed histologically at 4 and 7 days postinfection. To characterize PRRSV-infected cells and apoptotic cell death, we used immunohistochemical methods for detection of viral antigen, DNA electrophoresis for detection of DNA fragmentation, the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-fluorescein nick end labeling method for in situ detection of DNA strand breaks, and electron microscopy for ultrastructural morphologic studies. PRRSV infection resulted in widespread apoptosis in the lungs and lymphoid tissues of infected pigs. Virus infection-induced apoptotic cells were more abundant than PRRSV-infected cells in all tissues. DNA laddering was detected in lung and lymphoid tissues. However, double-labeling experiments demonstrated that the majority of apoptotic cells did not colocalize with PRRSV-infected cells. Our findings suggest the presence of an indirect mechanism in the induction of apoptosis for PRRSV.     

Immunity to porcine rubulavirus infection in adult swine

The immune response against the porcine rubulavirus was analyzed in experimentally infected adult pigs. High titers of virus neutralizing and hemagglutinating inhibitory antibodies were identified in infected animals. The antibody specificity was directed towards HN, M, and NP rubula virion proteins; immunodominance of HN proteins was demonstrated. Peripheral blood mononuclear cells from infected, but not from non-infected pigs proliferated in vitro in response to virus antigenic stimuli, showing a bell-shaped plot with the highest peak at 5 weeks post-infection. Virus-induced lymphoblasts expressed CD4+ CD8+ phenotype, whereas lectin-induced lymphoblasts were mainly identified as CD4+ CD8- cells. Phenotype analysis of freshly prepared PBMC revealed increased number of both monocytes (PoM1+) and total T lymphocytes (CD2+) early during infection, with reduced values of B lymphocytes at 4 weeks post-infection. Decrease in CD4+ CD8- blood cells was observed at 3 weeks post-infection, whereas both CD4- CD8+ and CD4+ CD8+ cells increased 1 and 4 weeks post-infection, respectively. This work discusses the relevance of CD4+ CD8+ T cells in the control of porcine rubulavirus infection.     

Mycoplasma hyopneumoniae potentiation of porcine reproductive and respiratory syndrome virus-induced pneumonia

An experimental model that demonstrates a mycoplasma species acting to potentiate a viral pneumonia was developed. Mycoplasma hyopneumoniae, which produces a chronic, lymphohistiocytic bronchopneumonia in pigs, was found to potentiate the severity and the duration of a virus-induced pneumonia in pigs. Pigs were inoculated with M. hyopneumoniae 21 days prior to, simultaneously with, or 10 days after inoculation with porcine reproductive and respiratory syndrome virus (PRRSV), which induces an acute interstitial pneumonia in pigs. PRRSV-induced clinical respiratory disease and macroscopic and microscopic pneumonic lesions were more severe and persistent in M. hyopneumoniae-infected pigs. At 28 or 38 days after PRRSV inoculation, M. hyopneumoniae-infected pigs still exhibited lesions typical of PRRSV-induced pneumonia, whereas the lungs of pigs which had received only PRRSV were essentially normal. On the basis of macroscopic lung lesions, it appears that PRRSV infection did not influence the severity of M. hyopneumoniae infection, although microscopic lesions typical of M. hyopneumoniae were more severe in PRRSV-infected pigs. These results indicate that M. hyopneumoniae infection potentiates PRRSV-induced disease and lesions. Most importantly, M. hyopneumoniae-infected pigs with minimal to nondetectable mycoplasmal pneumonia lesions manifested significantly increased PRRSV-induced pneumonia lesions compared to pigs infected with PRRSV only. This discovery is important with respect to the control of respiratory disease in pigs and has implications in elucidating the potential contribution of mycoplasmas in the pathogenesis of viral infections of other species, including humans.     

Metabolism of the carcinogen N-hydroxy-N-2-fluorenylacetamide by rat peritoneal neutrophils

A thymidine kinase (TK), inverted repeat, glycoprotein I (gI) and glycoprotein X (gpX) gene-deleted modified live virus pseudorabies vaccine was evaluated for safety in swine and for efficacy in protecting swine against challenge with pseudorabies virus (PRV). Safety was evaluated by inoculating pregnant gilts intravenously and 3-day-old pigs intracerebrally with the vaccine. Efficacy was evaluated by 1) vaccinating 3-day-old pigs with a minimal protective dose intranasally and then challenging with PRV 3 weeks postvaccination or 2) vaccinating weaned pigs with a standard field dose intramuscularly and then challenging with PRV 4 weeks postvaccination. The pigs vaccinated intranasally remained clinically normal following vaccination and challenge with PRV. The pigs vaccinated intramuscularly remained clinically normal following vaccination, but mild respiratory signs were seen in some of the vaccinated pigs following challenge with PRV. Humoral immune response was evaluated with enzyme-linked immunosorbent assays (ELISAs) and a serum virus neutralization test. All of the intramuscularly vaccinated pigs became gI and gpX positive on differential ELISAs following challenge. All of the intranasally vaccinated pigs were seropositive on the indirect gI ELISA following challenge, but not all of the pigs were seropositive on the blocking gI ELISA or the gpX ELISA 3 weeks postchallenge.     

Antigen-induced protective and nonprotective cell-mediated immune components against Cryptococcus neoformans

Mice immunized with two different cryptococcal antigen preparations, one a soluble culture filtrate antigen (CneF) in complete Freund's adjuvant (CFA) and the other heat-killed Cryptococcus neoformans cells (HKC), develop two different profiles of activated T cells. CneF-CFA induces CD4+ T cells responsible for delayed-type hypersensitivity (DTH) reactivity and for amplification of the anticryptococcal DTH response, whereas HKC induce CD4+ and CD8+ T cells involved in anticryptococcal DTH reactivity and activated T cells which directly kill C. neoformans cells. The main purpose of this study was to assess the level of protection afforded by each of the two different T-cell profiles against challenge with viable C. neoformans cells, thereby identifying which activated T-cell profile provides better protection. CBA/J mice immunized with CneF-CFA had significantly better protective responses, based on better clearance of C. neoformans from tissues, on longer survival times, and on fewer and smaller lesions in the brain, than HKC-immunized mice or control mice similarly infected with C. neoformans. Both immunization protocols induced an anticryptococcal DTH response, but neither induced serum antibodies to glucuronoxylmannan, so the protection observed in the CneF-CFA immunized mice was due to the activated T-cell profile induced by that protocol. HKC-immunized mice, which displayed no greater protection than controls, did not have the amplifier cells. Based on our findings, we propose that the protective anticryptococcal T cells are the CD4+ T cells which have been shown to be responsible for DTH reactivity and/or the CD4+ T cells which amplify the DTH response and which have been previously shown to produce high levels of gamma interferon and interleukin 2. Our results imply that there are protective and nonprotective cell-mediated immune responses and highlight the complexity of the immune response to C. neoformans antigens.     

Localization of alpha/beta and gamma/delta T lymphocytes in Cryptosporidium parvum-infected tissues in naive and immune calves

The nature of the host's T-lymphocyte population within the intestinal villi following Cryptosporidium parvum infection was characterized with a bovine model of cryptosporidiosis. In naive animals, infection with C. parvum resulted in substantial increases in the numbers of alpha/beta T cells, both CD4+ (150%) and CD8+ (60%), and of gamma/delta T cells (70%) present within the intestinal villi of the infected ileum. In immune animals, the host T-lymphocyte response to a challenge infection with C. parvum was restricted to alpha/beta T cells. The number of CD4+ T cells within the Peyer's patch of the ileum increased dramatically; however, there was little change in the number or localization of CD4+ T cells within the intestinal villi. In contrast, the number of CD8+ T cells within the intestinal villi increased following a challenge infection. In addition, the CD8+ T cells were found to be intimately associated with the epithelial cells of the intestinal villi. The precise correlation between the accumulation of CD8+ T cells and the normal site of parasite development suggests an important role for CD8+ T cells in the immune animal.     

Mechanisms of transmission of Aujeszky's disease virus originating from feral swine in the USA

To understand the possible mechanisms of transmission of Aujeszky's disease virus (pseudorabies or PRV) from a feral pig reservoir, intranasal infections were initiated in domestic pigs and in pigs from a herd derived from captured feral pigs. Virus strains originating from feral pigs and from domestic pigs were compared. Similar shedding patterns were obtained in both feral-derived and domestic pigs, however, virus strains from feral pigs were markedly attenuated. Virus could be isolated after acute infection from nasal secretions, tonsils and occasionally from genital organs. In studies of transmission of PRV by cannibalism, either latently infected or acutely infected tissue was fed to both domestic and feral-derived pigs. In two similar experiments, latently infected tissue did not transmit virus, but tissues from acutely infected pigs did transmit infection. Cannibalism was observed typically in both types of pigs older than 6 weeks of age. It was concluded that transmission of PRV originating from feral pigs can occur by several mechanisms including the respiratory route and by cannibalism of pigs that die of acute infection. Transmission of PRV from feral swine may, however, result in sub-clinical infection.     

Resistance to and recovery from lethal influenza virus infection in B lymphocyte-deficient mice

In the adaptive immune response to most viruses, both the cellular and humoral arms of the immune system play complementary roles in eliminating virus and virus-infected cells and in promoting recovery. To evaluate the relative contribution of CD4+ and CD8+ effector T lymphocytes in virus clearance and recovery, we have examined the host response to lethal type A influenza virus infection in B lymphocyte-deficient mice with a targeted disruption in the immunoglobulin mu heavy chain. Our results indicate that naive B cell-deficient mice have a 50- 100-fold greater susceptibility to lethal type A influenza virus infection than do wild type mice. However, after priming with sublethal doses of influenza, immune B cell-deficient animals show an enhanced resistance to lethal virus infection. This finding indicates that an antibody-independent immune-mediated antiviral mechanism accounts for the increased resistance to lethal virus challenge. To assess the contribution of influenza-specific CD4+ and CD8+ effector T cells in this process, defined clonal populations of influenza-specific CD4+ and CD8+ effector T cells were adoptively transferred into lethally infected B cell-deficient mice. Cloned CD8+ effectors efficiently promoted recovery from lethal infection, whereas cloned CD4+ T cells conferred only partial protection. These results suggest that memory T lymphocytes can act independently of a humoral immune response in order to confer resistance to influenza infection in immune individuals. The potential implications of these results for vaccination against human influenza infection are discussed.     

Effect on viraemia of an American and a European serotype PRRSV vaccine after challenge with European wild-type strains of the virus

Three groups of 10 pigs were vaccinated with an American serotype porcine reproductive and respiratory syndrome virus (PRRSV) vaccine and three groups of 10 pigs were vaccinated with a European serotype PRRSV vaccine. A control group of 12 pigs was left unvaccinated. Four weeks after vaccination the PRRSV-specific antibody titres were determined and each group was challenged with either a Spanish, German or Dutch PRRSV wild-type strain. The serological responses four weeks after vaccination confirmed that the two vaccines were of different serotypes. Vaccination with the American serotype vaccine hardly reduced the level of viraemia after challenge with the European PRRSV wild-type strains, and only after challenge with the Spanish PRRSV strain was a moderate, statistically significant reduction in viraemia observed. In contrast, after vaccination with the European serotype vaccine, viraemia was completely suppressed after challenge with the German PRRSV isolate and almost completely suppressed after challenge with the Spanish and Dutch PRRSV isolates.     

In vivo depletion of T-cells and cytokines during primary exposure of sheep to parasites

This study examined the role of CD8+ and WC1+ T-cells and of interferon (IFN)-gamma in the development of protective immunity against infection with the enteric nematode parasite Trichostrongylus colubriformis in sheep. Monoclonal antibodies (mAb) were administered during induction of the immune response to deplete or neutralise these components. Protection against the primary and challenge infections was assessed by faecal egg count and total worm count. Prolonged administration of mAb recognising IFN-gamma and CD8 resulted in significantly increased protection during the 6 week primary infection and following challenge. CD8+ cells were depleted from blood but not from intestinal mucosa. After injection of mAb (CC15) recognising the surface antigen WC1, WC1+ and Tcr gamma delta + cells were depleted from blood but not markedly from enteric mucosa, and protection against challenge, although variable, was increased by up to 88%. It appears that CD8+ and WC1+/gamma delta+ cells and IFN-gamma all retard the potential development of naturally acquired immunity against the parasite.     

Acute stress enhances while chronic stress suppresses cell-mediated immunity in vivo: a potential role for leukocyte trafficking

Delayed type hypersensitivity (DTH) reactions are antigen-specific, cell-mediated immune responses which, depending on the antigen involved, mediate beneficial (resistance to viruses, bacteria, fungi, and certain tumors) or harmful (allergic dermatitis, autoimmunity) aspects of immune function. We have shown that acute stress administered immediately before antigenic challenge results in a significant enhancement of a skin DTH response in rats. A stress-induced trafficking or redeployment of leukocytes to the skin may be one of the factors mediating this immunoenhancement. Here we investigate the effects of varying the duration, intensity, and chronicity of stress on the DTH response and on changes in blood leukocyte distribution and glucocorticoid levels. Acute stress administered for 2 h prior to antigenic challenge, significantly enhanced the DTH response. Increasing the duration of stress from 2 h to 5 h produced the same magnitude enhancement in cutaneous DTH. Moreover, increasing the intensity of acute stress produced a significantly larger enhancement of the DTH response which was accompanied by increasing magnitudes of leukocyte redeployment. In contrast, chronic stress suppressed the DTH response when it was administered for 3 weeks before sensitization and either discontinued upon sensitization, or continued an additional week until challenge, or extended for one week after challenge. The stress-induced redeployment of peripheral blood lymphocytes was attenuated with increasing exposure to chronic stress and correlated with attenuated glucocorticoid responsivity. These results suggest that stress-induced alterations in lymphocyte redeployment may play an important role in mediating the bi-directional effects of acute versus chronic stress on cell-mediated immunity in vivo.     

Contributions of antibody and T cell subsets to protection elicited by immunization with a replication-defective mutant of herpes simplex virus type 1

Replication-defective mutants of herpes simplex virus 1 (HSV-1) elicit immune responses in mice that reduce acute and latent infection after corneal challenge and are protective against development of disease. To understand the basis for the protective immunity induced by this new form of immunization, we investigated the contribution of various components of the immune response to protection against corneal infection and disease. Passive transfer of sera from mice immunized with the replication-defective mutant virus, d301, its parental HSV-1 strain, or uninfected cell lysate was used to examine the role of antibody. Despite posttransfer neutralizing antibody titers equivalent to those in control mice directly immunized with mutant virus, recipients of immune serum showed no reductions in primary replication in the eye, keratitis, or latent infection of the nervous system. However, immune serum protected mice from encephalitis and death. To examine the contribution of T cell subsets to protection, mice were immunized once with mutant virus and then were depleted in vivo of CD4+ or CD8+ T cells prior to corneal challenge. CD4 depletion resulted in higher titers of challenge virus in the eye at 3 to 4 days after challenge compared to control mice. Latent infection of the nervous system was increased by depletion of CD4+ T cells but not by depletion of CD8+ T cells keratitis developed only in a portion of the CD8+ T cell-depleted mice, suggesting that an immunopathologic potential of CD4+ T cells is held in check when immune CD8+ T cells are also present. Taken together, these data support a role for antibody induced by immunization with a replication-defective virus principally in protecting the central nervous system from disease, roles for CD4+ T cells in reducing primary replication in the eye and protecting against latent infection of the nervous system, and a role for CD8+ T cells in regulating the immunopathologic activity of CD4+ T cells.     

Altered cytokine production and impaired antimycobacterial immunity in protein-malnourished guinea pigs

Protein malnutrition leads to multiple detrimental alterations of host immune responses to mycobacterial infection. In this study, we demonstrated that splenocytes from low-protein (LP) guinea pigs vaccinated 6 weeks previously with attenuated Mycobacterium tuberculosis H37Ra failed to control the accumulation of virulent M. tuberculosis H37Rv in cocultured autologous peritoneal macrophages, despite the fact that they were able to control the accumulation of virulent tubercle bacilli in cocultured syngeneic peritoneal macrophages from normally nourished guinea pigs as successfully as did those from high-protein (HP) counterparts. Vaccine-induced growth control of virulent M. tuberculosis H37Rv in these cocultures appeared to be mediated by CD4 lymphocytes but not CD8 cells. Tuberculin (purified protein derivative [PPD])-induced lymphoproliferation was markedly impaired in vaccinated LP guinea pigs, and the depletion of CD4 lymphocytes significantly decreased lymphocyte proliferation whereas CD8 cell depletion did not. Protein malnutrition also impaired the abilities of cells from vaccinated LP guinea pigs to produce cytokines, including interferon, tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta), in response to PPD, despite the demonstration of higher serum levels of TNF-alpha and TGF-beta after an intravenous injection of PPD into LP guinea pigs. In contrast, peritoneal macrophages from protein-malnourished guinea pigs produced a higher level of TGF-beta 4 days after infection in vitro with M. tuberculosis H37Rv than did those from protein adequate controls. These results suggest that dietary protein malnutrition impairs vaccine-induced resistance to M. tuberculosis, in part, by altering the cytokine profile to favor macrophage deactivation.     

Protective immunity of bovine herpesvirus-1 (BHV-1) recombinants which express pseudorabies virus (PRV) glycoproteins gB, gC, gD and gE

We have constructed recombinants of bovine herpesvirus-1 (BHV-1) which express pseudorabies virus (PRV) gB, gC, gD or gE either individually or in combination. To test the protective immunity, mice were inoculated with these BHV-1 recombinants and challenged three weeks later with virulent PRV. A BHV-1 recombinant, BHV-1/TF7-1, which express PRV gC, gD, gE and gI but not PRV gB, protected all 7 mice from the challenge with 20 LD50 virulent PRV and 6 out of 7 from the challenge with 100 LD50 PRV, while one dead mice survived for 5 days after the challenge. All the control mice died in 3 days. BHV-1 recombinants which express PRV gB, gC and gD individually also gave some protection but not so effective as BHV/TF7-1. Before challenging with virulent PRV, sera were collected from immunized mice and antibody against PRV was assayed. Western blot analyses indicated that all the recombinants induced antibody in mice against PRV gB, gC or gD individually or in combination. Virus neutralizing (VN) titer against PRV was highest in mice which were inoculated with BHV-1/TF6-1, which expresses PRV gB. BHV-1/TF7-1, which was more effective to protect mice from the challenge of virulent PRV, induced lower VN titer.     

Seroprevalence of porcine reproductive and respiratory syndrome virus in Dutch weaning pigs

To determine whether under Dutch field conditions PRRSV infection occurs in weaning pigs before the finishing period, a cross-sectional study was performed on 32 breeding farms to estimate the seroprevalence of antibodies directed against PRRSV in 4- to 5-week-old and 8- to 9-week-old pigs. Farms were visited twice within 5 months, and during each sampling an average of 20 sera were randomly collected from a unit of 4- to 5-week-old and a unit of 8- to 9-week-old pigs. The sera (n = 2568) were tested in the IDEXX-ELISA for the presence of antibodies directed against PRRSV. The seroprevalence of PRRSV in 4- to 5-week-old pigs and 8- to 9-week-old pigs varied between both samplings for each farm. The seroprevalence in the younger pigs was significantly higher than in the older pigs for both samplings (p < 0.05), suggesting the presence of maternal antibodies. In addition, a longitudinal study was performed to evaluate the IDEXX-ELISA in detecting maternal antibodies directed against PRRSV and to determine the rate of decline of these antibodies in field sera. From serological results of eight litters, an average decay function was computed to quantify the maternal immunity to PRRSV. A seroprevalence in 8- to 9-weeks-old pigs of > or = 0.20 was calculated to indicate an active immune response to PRRSV. In the cross-sectional study in the pigs twenty-three percent of the units with 8- to 9-week-old pigs were considered to have an active serological response against PRRSV. We conclude that most Dutch pigs are seronegative for PRRSV at the start of the finishing period, since the results of this study showed that 77% of the units with 8- to 9-week-old pigs had a seroprevalence < 0.20.     

IL-15 augments CD8+ T cell-mediated immunity against Toxoplasma gondii infection in mice

Cytokines of the Th1 profile are important mediators of protective host immunity against Toxoplasma gondii infection in mice. In this study we describe the effect of the recently identified cytokine, IL-15, on prevention of murine infection with T. gondii. Administration of exogenous rIL-15 with soluble Toxoplasma lysate Ag (TLA) provides complete protection against a lethal parasite challenge, whereas treatment with either rIL-15 or TLA alone is not protective. Following immunization with TLA/rIL-15, there is a significant proliferation of splenocytes expressing the CD8+ phenotype in response to TLA. A significant rise in the level of serum IFN gamma was observed in vaccinated mice. Adoptive transfer of CD8+ T cells, but not CD4+ T cells, from TLA/rIL-15-vaccinated mice protects naive mice from a lethal parasite challenge. These CD8+ T cells exhibit enhanced CTL activity against target macrophages infected with T. gondii. Mice that have been immunized are protected against lethal parasite challenge for at least 1 mo postvaccination. These observations demonstrate that TLA when administered with exogenous rIL-15 generates toxoplasmacidal Ag-specific CD8+ T cells. These T cells proliferate upon exposure to parasite Ag, exhibit long term memory CTL against infected target cells, and may be involved in host immune memory to this parasite.