A Virus-like Particle-Based F4 Enterotoxigenic Escherichia coli Vaccine Is Inhibited by Maternally Derived Antibodies in Piglets but Generates Robust Responses in Sows.

F4-positive enterotoxigenic Escherichia coli is associated with diarrhea and poor growth outcomes in neonatal and newly weaned piglets and is thus a major economic and welfare burden in the swine industry. Vaccination of sows with F4 fimbriae protects against the neonatal disease via passive transfer of maternal immunity. However, this strategy does not protect against infection post-weaning. Consequently, prevention and treatment methods in weaner pigs heavily rely on the use of antimicrobials. Therefore, in order to reduce antimicrobial consumption, more effective prophylactic alternatives are needed. In this study, we describe the development of a capsid virus-like particle (cVLP)-based vaccine targeting the major F4 fimbriae subunit and adhesion molecule, FaeG, and evaluate its immunogenicity in mice, piglets, and sows. cVLP-display significantly increased systemic and mucosal antibody responses towards the recombinant FaeG antigen in mice models. However, in piglets, the presence of anti-F4 maternally derived antibodies severely inhibited the induction of active humoral responses towards the FaeG antigen. This inhibition could not be overcome, even with the enhanced immunogenicity achieved via cVLP display. However, in sows, intramuscular vaccination with the FaeG.cVLP vaccine was able to generate robust IgG and IgA responses that were comparable with a commercial fimbriae-based vaccine, and which were effectively transferred to piglets via colostrum intake. These results demonstrate that cVLP display has the potential to improve the systemic humoral responses elicited against low-immunogenic antigens in pigs; however, this effect is dependent on the use of antigens, which are not the targets of pre-existing maternal immunity.

Descriptive analyses of maternally-derived antibody levels against porcine circovirus 2 (PCV-2) in 3- and 21-day-old piglets from farms of four European countries using different vaccination protocols in sows.

BACKGROUND: Up to now, information on the levels of maternally-derived antibodies (MDA) against PCV-2 in suckling piglets born to sows vaccinated with different strategies is scarce in the literature. In the present observational study, the PCV-2-specific MDA titres from piglets from 109 farms (thirty 3-day-old and thirty 21-day-old piglets per farm) across four different European countries (France n = 30, Germany n = 27, Italy n = 22 and Spain n = 30) using different sow vaccination strategies (during gestation, as a gilt, as a piglet or never) were assessed. RESULTS: In all four countries, mean log PCV-2 MDA titres were higher in 3-day-old piglets than in the 3-week-old ones, being significant in most of all the comparisons performed. Within each country, the highest PCV-2-specific MDA titres were observed in the 3-day-old piglets born to sows vaccinated during gestation. Indeed, in the four countries, more than 60% of this subpopulation (3-day-old piglets from sows vaccinated during pregnancy) had the highest log PCV-2 titres detectable with the ELISA technique used in this study. The lowest MDA titres were more variable. Whereas in France and Germany the lowest titres corresponded to 21-day-old piglets born from sows vaccinated as a piglet, in Italy, they corresponded to 21-day-old piglets derived from sows vaccinated as a gilt and in Spain to 21-day-old piglets born from non-vaccinated sows. In this study, PCV-2-specific MDA titres at 3 and 21 days of age were not affected by sow parity. CONCLUSIONS: Data obtained could be considered as a European global overview of PCV-2-specific MDA titres present in the pre-vaccinated piglet populations in different European countries, with titres tending to be higher in younger piglets, but with values variable among countries and sow vaccination strategies.

Effect of influenza A virus sow vaccination on infection in pigs at weaning: A prospective longitudinal study.

Although vaccination is the main measure to control influenza A virus (IAV) in swine, there is limited information on the efficacy of sow vaccination on reducing IAV infections in pigs at weaning. We assessed the effect of sow vaccination on IAV infection in pigs at weaning in a cohort of 52 breeding herds studied prospectively. Herds were voluntarily enrolled according to their IAV history, sow vaccination protocol and monitored during six months (prospective longitudinal study). On each herd, nasal swabs were collected monthly from 30 pigs at weaning and tested for IAV by RT-PCR. IAV was detected in 25% (75/305) of sampling events. Of 9,150 nasal swab pools (3 individual nasal swabs/pool), 15% (458/3050) of pools tested IAV positive. IAV infections in pigs at weaning were lower in vaccinated herds compared to non-vaccinated ones. Moreover, no significant differences were seen between prefarrow and whole herd protocols, or the use of commercial versus autogenous IAV vaccines. Prefarrow and whole herd vaccination protocols reduced the odds of groups testing IAV positive at weaning in comparison with no vaccination. Our results are relevant when considering implementation of sow vaccination to control influenza infections in pigs at weaning and, hence, minimize transmission to growing pigs and other farms.

Effects of pre-farrowing sow vaccination against Mycoplasma hyopneumoniae on offspring colonisation and lung lesions.

This study investigated Mycoplasma hyopneumoniae colonisation and lung lesions at slaughter in pigs from vaccinated (V) and non-vaccinated (NV) sows, in two herds (A and B). In each herd, two sow batches were V against M. hyopneumoniae with a commercial bacterin at six and three weeks before farrowing and two sow batches remained NV. From each sow batch, laryngeal swabs were collected from the litters of five primiparous sows at weaning and seven days post-weaning. All samples were tested for M. hyopneumoniae by nested PCR. In total, 488 piglets were sampled. At slaughter, the extent of Mycoplasma-like pneumonia lesions (lung lesion score (LLS)) was assessed. The colonisation rates with M. hyopneumoniae at weaning and seven days post-weaning were (V-A=14.2, NV-A=20.0 (P=0.225); V-B=0.9, NV-B=0.8 (P=0.948)) and (V-A=0.8, NV-A=7.0 (P=0.039); V-B=1.8, NV-B=2.5 (P=0.738)), respectively. The average LLS (in per cent) was V-A=15.5, NV-A=26.4 (P=0.021); V-B=9.7, NV-B=8.4 (P=0.541). In conclusion, in herd A, with a substantially higher level of piglet colonisation at weaning than herd B, offspring from V sows had a significantly lower colonisation rate seven days post-weaning and a significantly lower LLS at slaughter compared with the offspring of the NV sows. This implies that sow vaccination might be useful for control of M. hyopneumoniae infections, although significant results may not be achieved at all times (such as in herd B).

Comparison of cytokine profiles in peripheral blood mononuclear cells between piglets born from Porcine circovirus 2 vaccinated and non-vaccinated sows.

This study was aimed to evaluate the effect of Porcine circovirus 2 (PCV2) sow vaccination on cell-mediated immune responses in sows and their progeny. At 7 weeks before farrowing, fifteen PCV2 PCR negative pregnant sows with medium-low antibody values were selected and randomly distributed in two groups according to the antibody levels. Seven sows were vaccinated with a commercial PCV2 vaccine and eight were injected with phosphate-buffered saline at 6 and 3 weeks before farrowing. Blood samples were taken from sows and their piglets (n = 90) during the study duration. PCV2 DNA and antibodies were tested in sera, and cytokine (IFN-α, IFN-γ, IL-12p40, TNF-α, IL-1ß, IL-8, IL-4, IL-6 and IL-10) levels were assessed in supernatant from cultured peripheral blood mononuclear cells. All sows and piglets were negative by PCV2 PCR throughout the study. Significantly higher PCV2 antibody levels were detected in vaccinated sows after vaccination and in their offspring after colostrum ingestion compared to the non-vaccinated counterparts. Vaccinated sows did not show significant differences in cytokine secretion levels at farrowing compared to unvaccinated dams. In contrast, piglets from vaccinated sows had significantly higher levels of cytokines linked to Th1 memory cells (IFN-γ and TNF-α) in comparison to the ones from non-vaccinated dams. In conclusion, PCV2 sow vaccination, apart from triggering a humoral immunity response in sows and their progeny, might be associated to an increased transfer of cell-mediated immunity from the dam to the piglet.

Latent porcine circovirus type 2-infected domestic pigs: A potential infection model for the effective development of vaccines against latent or chronic virus induced diseases.

Until recently, knowledge of the pathogenicity of Circoviridae and Anelloviridae family members was limited. Our previous discoveries provided clues toward resolving this issue based on studies of the latent nature of porcine circovirus type 2 (PCV2) genotype group members. We developed a conventional pig infection model that indicated that weaners already harbored latent PCV2 infection in the thymus, which enabled the viruses to specifically modulate the maturation of T-helper cells. This finding raised the possibility that the thymi of normal fetuses were already infected with PCV2. The present findings further substantiate our hypothesis that PCV2 masquerades as the host by infecting fetuses before they acquire immune-competence. We provide the first demonstration that all domestic pig fetuses preferentially harbor latent PCV2-infected cells in their thymi. These PCV2-infected cells are different from thymocytes and are located in the medulla of the fetal thymus. These latent PCV2-infected cells in fetuses are found at the same location and share characteristics with the infected cells observed in adolescent pigs. Moreover, fetuses also harbor these infected cells in other lymph system organs. We provide the first demonstration that the fetal thymus virus pools are minimally affected by sow vaccination, highlighting the immune-privileged character of this organ. Furthermore, we found a striking reduction in virus-infected cells in the fetal spleen and an increase in PCV2-infected cells in the fetal intestine of anti-PCV2-vaccinated mothers. These data indicate that specific immune response interactions occur between mothers and their progeny that are not dependent on the humoral immunity of the mother and cannot be attributed to the rudimentary humoral responses of the fetuses because these pig fetuses do not have any PCV2-specific antibodies. These shifts in our understanding of the PCV2-infected cell pool will lead to different avenues in the search for effective vaccination strategies against latent and chronic pathogens.