RESUMO
Little is known about the influence of maternal antibodies and immune cells transferred through colostrum on the immune responses of calves to the currently used foot-and-mouth disease (FMD) vaccines. Here we evaluated the humoral and cellular immune responses induced by vaccination of colostrum-deprived calves and calves that received equivalent amounts of colostrum preparations that differed in the presence or absence of maternal immune cells but contained the same quantity and quality of anti-foot-and-mouth disease virus (FMDV) antibodies. Three groups of 32-d-old calves (n = 3 per group) were deprived of colostrum and fed either whole immune colostrum or a cell-free colostrum preparation containing only anti-FMDV antibodies. All groups were immunized with 1 dose of an oil-adjuvanted commercial vaccine. Blood samples were collected periodically before vaccination and weekly after vaccination. Immune responses specific to FMDV were assessed based on T-cell proliferation, IFN-γ production, total and neutralizing serum antibodies, and isotype profile. All vaccinated calves developed IFN-γ and lymphoproliferative responses, irrespective of the colostrum received. Colostrum-deprived animals responded to vaccination with a primary IgM response followed by an increase of IgG1 titers. Conversely, antibody titers decreased in all colostrum-fed calves after vaccination. This study demonstrates for the first time that maternal immune cells transferred to the calves through colostrum do not modify immune responses to FMD vaccine, and it confirms the interference of maternal antibodies in the induction of humoral but not cell-mediated immune responses.
Assuntos
Doenças dos Bovinos/imunologia , Colostro/imunologia , Febre Aftosa/imunologia , Vacinas Virais/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais/sangue , Bovinos , Doenças dos Bovinos/prevenção & controle , Feminino , Imunidade Celular , Imunogenicidade da Vacina , Gravidez , Vacinação/veterináriaRESUMO
Neospora caninum, an intracellular protozoan parasite from the phylum Apicomplexa, is the etiologic agent of neosporosis, a disease considered as a major cause of reproductive loss in cattle and neuromuscular disease in dogs. Bovine neosporosis has a great economic impact in both meat and dairy industries, related to abortion, premature culling and reduced milk yields. Although many efforts have been made to restrain bovine neosporosis, there are still no efficacious control methods. Many vaccine-development studies focused in the apicomplexan proteins involved in the adhesion and invasion of the host cell. Among these proteins, profilins have recently emerged as potential vaccine antigens or even adjuvant candidates for several diseases caused by apicomplexan parasites. Profilins bind Toll-like receptors 11 and 12 initiating MyD88 signaling, that triggers IL-12 and IFN-γ production, which may promote protection against infection. Here we summarized the state-of-the-art of novel vaccine development based on apicomplexan profilins applied as antigens or adjuvants, and delved into recent advances on N. caninum vaccines using profilin in the mouse model and in cattle.
Assuntos
Apicomplexa/química , Doenças dos Bovinos/prevenção & controle , Coccidiose/veterinária , Neospora/imunologia , Profilinas/imunologia , Vacinas Protozoárias , Animais , Apicomplexa/imunologia , Bovinos , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/parasitologia , Galinhas , Coccidiose/imunologia , Coccidiose/prevenção & controle , Modelos Animais de Doenças , CamundongosRESUMO
Innate immune cells show enhanced responsiveness to secondary challenges after an initial non-related stimulation (Trained Innate Immunity, TII). Acute NOD2 activation by Muramyl-Dipeptide (MDP) promotes TII inducing the secretion of pro-inflammatory mediators, while a sustained MDP-stimulation down-regulates the inflammatory response, restoring tolerance. Here we characterized in-vitro the response of murine macrophages to lipopolysaccharide (LPS) challenge under NOD2-chronic stimulation. RAW264.7 cells were trained with MDP (1 µg/ml, 48 h) and challenged with LPS (5 µg/ml, 24 h). Trained cells formed multinucleated giant cells with increased phagocytosis rates compared to untrained/challenged cells. They showed a reduced mitochondrial activity and a switch to aerobic glycolysis. TNF-α, ROS and NO were upregulated in both trained and untrained cultures (MDP+, MDP- cells, p > 0.05); while IL-10, IL-6 IL-12 and MHCII were upregulated only in trained cells after LPS challenge (MDP + LPS+, p < 0.05). A slight upregulation in the expression of B7.2 was also observed in this group, although differences were not statistically significant. MDP-training induced resistance to LPS challenge (p < 0.01). The relative expression of PARP-1 was downregulated after the LPS challenge, which may contribute to the regulatory milieu and to the innate memory mechanisms exhibited by MDP-trained cells. Our results demonstrate that a sustained MDP-training polarizes murine macrophages towards a M2b profile, inhibiting parthanatos. These results may impact on the development of strategies to immunomodulate processes in which inflammation should be controlled.
RESUMO
Effective Foot and Mouth Disease Virus (FMDV) peptide vaccines for cattle have two major constraints: resemblance of one or more of the multiple conformations of the major VP1 antigenic sites to induce neutralizing antibodies, and stimulation of T cells despite the variable bovine-MHC polymorphism. To overcome these limitations, a chimeric antigen was developed, using Vesicular Stomatitis Virus glycoprotein (VSV-G) as carrier protein of an in tandem-dimer of FMDV antigenic site A (ASA), the major epitope on the VP1 capsid protein (aa 139-149, FMDV-C3 serotype). The G-ASA construct was expressed in the Baculovirus system to produce a recombinant protein (DEL BAC) (cloned in pCDNA 3.1 plasmid) (Invitrogen Corporation, Carlsbad, CA) and was also prepared as a DNA vaccine (pC DEL). Calves vaccinated with both immunogens elicited antibodies that recognized the ASA in whole virion and were able to neutralize FMDV infectivity in vitro. After two vaccine doses, DEL BAC induced serum neutralizing titers compatible with an "expected percentage of protection" above 90%. Plasmid pC DEL stimulated FMDV specific humoral responses earlier than DEL BAC, though IgG1 to IgG2 ratios were lower than those induced by both DEL BAC and inactivated FMDV-C3 after the second dose. DEL BAC induced FMDV-specific secretion of IFN-γ in peripheral blood mononuclear cells of outbred cattle immunized with commercial FMDV vaccine, suggesting its capacity to recall anamnestic responses mediated by functional T cell epitopes. The results show that exposing FMDV-VP1 major neutralizing antigenic site in the context of N-terminal sequences of the VSV G protein can overcome the immunological limitations of FMDV-VP1 peptides as effective protein and DNA vaccines for cattle.