DISCUSIN
Foot-and-mouth disease (FMD) is an acute infectious viral disease characterized by producing vesicular lesions in tissues of the oronasal mucosa (including the tongue and palate), udders, interdigital spaces and coronary runners of the hooves of infected animals. Its etiological agent,\nthe foot-and...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Ciencias Veterinarias
2019
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=avaposgra&cl=CL1&d=HWA_2835 https://repositoriouba.sisbi.uba.ar/gsdl/collect/avaposgra/index/assoc/HWA_2835.dir/2835.PDF |
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| Sumario: | Foot-and-mouth disease (FMD) is an acute infectious viral disease characterized by producing vesicular lesions in tissues of the oronasal mucosa (including the tongue and palate), udders, interdigital spaces and coronary runners of the hooves of infected animals. Its etiological agent,\nthe foot-and-mouth disease virus (FMDV), is a virus belonging to the Picornaviridae family that\naffects cloven-hoofed animals, including cattle, pigs, goats and domestic sheep, along with\nnumerous wild species that can act as reservoirs under certain ecological conditions The virulence, the wide range of hosts, the diversity of variants and the high infectious and contagious\ncapacity of FMDV, explain their presence and re-emergence in various parts of the world and make it a sanitary problem of scale global. The disease generates enormous economic losses to the livestock industry due to the forced closure of external markets and considerable losses in the domestic market, associated with the reduction of production, slaughter, and blockage of animal movement.\nPrevious results of our laboratory described the onset of the mucosal and systemic immunity\nin cattle not only after FMDV aerosol infection but also after systemic vaccination, showing that the response is independent of the initial route of contact with the virus. Despite this, the\ncontribution of each immune mechanism implicated in the immune response is not clear yet. The present work is based on the hypothesis that the systemic antibodies circulating after a passive\nimmunization in cattle are sufficient to prevent disease generalization after oronasal infection and in absence of additional immune mechanisms. To this end, a series of experiments were initially carried out to adjust the conditions for the\npassive immunization against FMD in seronegative calves. In these procedures, calves sera from\ncattle vaccinated with commercial tetravalent formulations were used. From these results, the\nvolume of serum required to make the passive immunization was determined, as well as the\nadministration protocols and the time available to perform the subsequent infections in the passively immunized animals. For the final experiment, naïve animals (n=8) received one dose of a single-oil-emulsion\nmonovalent vaccine containing FMDV O1/Campos strain. We used two different preparations of\nFMDV- specific immune serum, obtained at 7 and 26 days post-vaccination (dpv), differing therefore in the immunoglobulin isotype composition and seroneutralization titers. Serum 7 dpv\npool had a titer of neutralizing antibodies of 1.6 and the isotype predominantly on its composition\nwas IgM, while titer of serum 26 dpv pool was 2.7 and both subtypes- IgG1 and IgG2- were detected in the pool and in less concentration IgM. After passive immunization, animals were infected by oronasal infection with FMDV O1C strain and these results were compared with\nanimals infected 7 and 26 days after vaccination.\nOur results demonstrated that systemic antibodies were enough to prevent the disease generalization only in the case of animals transferred with serum 26 dpv, since animals transferred with serum 7 dpv showed clinical symptoms of the disease after oronasal infection. This might\nsuggest that in absence of other preexisting adaptive immune mechanisms, circulating antibodies\nare able to prevent the progress of the disease despite there is a threshold titer of antibodies below\nwhich the disease is triggered after oronasal infection. Animals infected after vaccination were all protected, including the animal vaccinated and\ninfected 7 dpv even though when the neutralizing antibody titers were similar to those of the animals passively immunized with serum 7 dpv and which showed clinical symptoms after oronasal infection. The study of post-infection antibody responses, both systemic and mucosal,\nindicated that vaccination promoted the generation of a rapid antibody response after exposure to\nthe virus, presenting a secondary response profile. In both cases, those infected at 7 dpv or at 26\ndpv showed rapid changes of the predominant isotype of the FMDV-specific immunoglobulins, as\nwell as an increase in antibody titers and avidity in sera obtained post-infection. Interestingly, these\nobservations were verified both at the systemic and local level, in draining lymph nodes of the respiratory tract. Overall, these results indicate that circulating antibodies may be sufficient to prevent the\ngeneralization of the disease in bovines infected by the oronasal route, even in the absence of other active mechanisms of specific immunity. In turn, the characterization of post-challenge antibody responses, both at systemic and local level, revealed that systemic immunization with\nconventional anti-FMDV vaccines rapidly promoted increases in antibody titers and avidity of the immune serum, accompanied by a change of the isotype profile towards the IgG1 subclass, all changes associated with anamnestic responses against the virus. Interestingly, such protective\nresponses occurred very early after vaccination (7 dpv) and even when the aerogenic infection\nwas performed in the presence of low titers of FMDV-neutralizing antibodies. |
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