RESUMEN
Mycoplasma gallisepticum causes coughing, ocular and nasal discharge, reduction in feed intake, lower and uneven growth, decline in egg production and quality, and increase in mortality. Among the attenuated vaccination strains, MGF can reduce clinical signs and lesions in layer hens, stimulate immune responses of cellular and humoral basis, act as an instrument of competitive exclusion in relation to field strains, and reduce the use of antimicrobials. This study aimed to investigate the effects of attenuated MG F-strain vaccination on egg quality in 3 groups of 30 hens each, being one control and 2 vaccinated. Vaccination was applied by ocular route at 8 and 12 wk of age. Comparisons were made among unvaccinated hens; vaccinated at 8 wk of age; and vaccinated at 8 and 12 wk of age. There were no statistical differences in eggshell thickness and weight among groups. Eggs from twice vaccinated birds yielded a Haugh unit significantly lower than the other groups without affecting egg classification. There was no significant difference in ELISA results between the vaccinated groups.
Asunto(s)
Vacunas Bacterianas/farmacología , Pollos , Cáscara de Huevo/efectos de los fármacos , Mycoplasma gallisepticum/inmunología , Óvulo/efectos de los fármacos , Animales , Vacunas Bacterianas/administración & dosificación , Relación Dosis-Respuesta Inmunológica , Cáscara de Huevo/fisiología , Femenino , Infecciones por Mycoplasma/microbiología , Infecciones por Mycoplasma/prevención & control , Infecciones por Mycoplasma/veterinaria , Óvulo/fisiología , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/prevención & control , Vacunación/veterinaria , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/farmacologíaRESUMEN
In this study, the immune response induced by a mixture of polysaccharide and nucleic acid extracted from Bacillus Calmette-Guerin (BCG) was evaluated in chickens inoculated with infectious bursal disease virus (IBDV) vaccine. After the mixture was injected intramuscularly at a dose of 0.075, 0.15 or 0.3 mg·kg(-1)·day(-1) for 3 days, the 14-day-old chickens were inoculated with the attenuated IBDV vaccine via intranasal and ocular routes. The relative weight of bursa of Fabricius (BF) and thymus, the serum IBD antibody titer, the CD4+/CD8+ ratio, and the concentrations of IFN-γ, IL-2 and IL-6 in peripheral blood were investigated on days 5, 15 and 25. The IBD antibody titer in BCG-treated groups was higher than in the negative control and only IBD-vaccinated chickens, indicating that the mixture of BCG can significantly enhance chicken humoral response. CD4+/CD8+ and the secretions of IFN-γ, IL-2 and IL-6 were also clearly increased compared with that in the negative control and IBD-vaccinated chickens, indicating that the mixture can also enhance the cell-mediated immune response. The results also showed that the relative weights of BF and thymus increased after chickens were inoculated with BCG, indicating that the BCG mixture can clearly enhance the immunity of IBD-vaccine and can be expected to be viewed as a candidate for a new type of immune adjuvant.
Asunto(s)
Vacuna BCG/inmunología , Infecciones por Birnaviridae/veterinaria , Virus de la Enfermedad Infecciosa de la Bolsa/inmunología , Ácidos Nucleicos/inmunología , Polisacáridos/inmunología , Enfermedades de las Aves de Corral/inmunología , Adyuvantes Inmunológicos/farmacología , Animales , Anticuerpos Antivirales/sangre , Vacuna BCG/química , Vacuna BCG/farmacología , Infecciones por Birnaviridae/inmunología , Pollos/inmunología , Virus de la Enfermedad Infecciosa de la Bolsa/metabolismo , Masculino , Ácidos Nucleicos/aislamiento & purificación , Ácidos Nucleicos/farmacología , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Enfermedades de las Aves de Corral/terapia , Distribución Aleatoria , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/farmacología , Vacunas de ADN/administración & dosificación , Vacunas de ADN/farmacología , Vacunas Virales/inmunología , Vacunas Virales/farmacologíaRESUMEN
Rotavirus is the most common cause of severe gastroenteritis in young children worldwide. The introduction of vaccination programs has led to a significant reduction in number of hospitalizations due to rotavirus in North and South American countries. Little work has been done, however, to examine the differential impact of vaccination as a function of strain distribution and strain-specific vaccine efficacy. We developed a two-strain epidemiological model of rotavirus transmission, and used it to examine the effects of a monovalent vaccine (Rotarix) on the qualitative behaviors of infection levels in a population. For contrast, we parameterized our model with strain distribution data from North America and from South America. In all cases, the introduction of the vaccine led to significant decreases in the prevalence of primary infection due to both strains for a decade or more, after which the overall prevalence recovers to near pre-vaccination levels. The prevalence of G1P[8] is significantly higher in North America (73 % of all rotavirus infections) compared to that in South America (34 %). Our model predicts that the introduction of Rotarix might result in major strain replacement in regions such as North America where the prevalence of G1P[8] is relatively high, due to higher efficacy of Rotarix against infection caused by G1P[8], while regions with lower prevalence of G1P[8], such as South America, are not susceptible to major strain replacement.
Asunto(s)
Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/farmacología , Número Básico de Reproducción , Humanos , Lactante , Conceptos Matemáticos , Modelos Biológicos , América del Norte/epidemiología , Rotavirus/clasificación , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , América del Sur/epidemiología , Vacunas Atenuadas/farmacologíaRESUMEN
Previously, we showed that genetically modified live-attenuated Leishmania donovani parasite cell lines (LdCen(-/-) and Ldp27(-/-)) induce a strong cellular immunity and provide protection against visceral leishmaniasis in mice. In this study, we explored the mechanism of cross-protection against cutaneous lesion-causing Leishmania mexicana. Upon challenge with wild-type L. mexicana, mice immunized either for short or long periods showed significant protection. Immunohistochemical analysis of ears from immunized/challenged mice exhibited significant influx of macrophages, as well as cells expressing MHC class II and inducible NO synthase, suggesting an induction of potent host-protective proinflammatory responses. In contrast, substantial inhibition of IL-10, IL-4, and IL-13 expression and the absence of degranulated mast cells and less influx of eosinophils within the ears of immunized/challenged mice suggested a controlled anti-inflammatory response. L. mexicana Ag-stimulated lymph node cell culture from the immunized/challenged mice revealed induction of IFN-γ secretion by the CD4 and CD8 T cells compared with non-immunized/challenged mice. We also observed suppression of Th2 cytokines in the culture supernatants of immunized/challenged lymph nodes compared with non-immunized/challenged mice. Adoptively transferred total T cells from immunized mice conferred strong protection in recipient mice against L. mexicana infection, suggesting that attenuated L. donovani can provide protection against heterologous L. mexicana parasites by induction of a strong T cell response. Furthermore, bone marrow-derived dendritic cells infected with LdCen(-/-) and Ldp27(-/-) parasites were capable of inducing a strong proinflammatory response leading to the proliferation of Th1 cells. These studies demonstrate the potential of live-attenuated L. donovani parasites as pan-Leishmania species vaccines.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Inmunidad Celular/efectos de los fármacos , Leishmania donovani/inmunología , Leishmania mexicana/inmunología , Vacunas contra la Leishmaniasis/farmacología , Leishmaniasis Cutánea/prevención & control , Animales , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/patología , Reacciones Cruzadas/efectos de los fármacos , Citocinas/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Inmunidad Celular/genética , Leishmania donovani/genética , Vacunas contra la Leishmaniasis/genética , Vacunas contra la Leishmaniasis/inmunología , Leishmaniasis Cutánea/genética , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/patología , Macrófagos/inmunología , Ratones , Ratones Endogámicos BALB C , Vacunas Atenuadas/farmacologíaRESUMEN
Mycobacterium habana was isolated in Cuba in 1971. Later, was demonstrated its protection capacity in mycobacterial infection. Here we determined the level of virulence, immunogenicity and the efficacy of three different M. habana strains as attenuated live vaccines. Intratracheal infection of BALB/c mice with high dose M. habana TMC 5135 or IPK-337 strains permitted 100% survival and limited tissue damage. Mice infected with M. habana IPK-220 showed lower attenuation, so it was discarded for the vaccination experiments. Strains IPK-337 and TMC 5135 were used as subcutaneous vaccine and compared with BCG. Nude mice vaccinated with strain 5135 showed longer but non-significant survival than BCG vaccinated animals. Cell suspensions from M. habana vaccinated mice produced higher IFNγ after stimulation with mycobacterial antigens than BCG recipients. After four months of challenge with Mycobacterium tuberculosis strain H37Rv, mice vaccinated with BCG substrain Phipps or strain TMC 5135 showed total survival, while 60% survival was exhibited by animals vaccinated with M. habana IPK-337. Both M. habana strains do not prevent the infection with M. tuberculosis but avoided the progression of the experimental disease; strain TMC 5135 showed similar level of protection than BCG.
Asunto(s)
Micobacterias no Tuberculosas/inmunología , Vacunas contra la Tuberculosis/farmacología , Tuberculosis Pulmonar/inmunología , Animales , Modelos Animales de Enfermedad , Inmunidad Celular , Estimación de Kaplan-Meier , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Interferón/metabolismo , Tuberculosis Pulmonar/patología , Tuberculosis Pulmonar/prevención & control , Factor de Necrosis Tumoral alfa/metabolismo , Vacunas Atenuadas/farmacología , Virulencia , Receptor de Interferón gammaRESUMEN
No commercially live vaccine against cholera caused by Vibrio cholerae O139 serogroup is available and it is currently needed. Virulent O139 strain CRC266 was genetically modified by firstly deleting multiple copies of the filamentous phage CTXφ, further tagging by insertion of the endoglucanase A coding gene from Clostridium thermocellum into the hemagglutinin/protease gene and finally deleting the mshA gene, just to improve the vaccine biosafety. One of the derived strains designated as TLP01 showed full attenuation and good colonizing capacity in the infant mouse cholera model, as well as highly immunogenic properties in the adult rabbit and rat models. Since TLP01 lacks MSHA fimbriae, it is refractory to infection with another filamentous phage VGJφ and therefore protected of acquiring CTXφ from a recombinant hybrid VGJφ/CTXφ. This strategy could reduce the possibilities of stable reversion to virulence out of the human gut. Furthermore, this vaccine strain was impaired to produce biofilms under certain culture conditions, which might have implications for the strain survival in natural settings contributing to vaccine biosafety as well. The above results has encouraged us to consider TLP01 as a live attenuated vaccine strain having an adequate performance in animal models, in terms of attenuation and immunogenicity, so that it fulfills the requirements to be evaluated in human volunteers.
Asunto(s)
Vacunas contra el Cólera/inmunología , Proteínas Fimbrias/inmunología , Vibrio cholerae O139/inmunología , Administración Oral , Animales , Anticuerpos Antibacterianos/inmunología , Derrame de Bacterias , Secuencia de Bases , Biopelículas , Cólera/inmunología , Cólera/prevención & control , Vacunas contra el Cólera/genética , Vacunas contra el Cólera/farmacología , Modelos Animales de Enfermedad , Heces/microbiología , Proteínas Fimbrias/genética , Mucosa Intestinal/inmunología , Lectina de Unión a Manosa/genética , Lectina de Unión a Manosa/inmunología , Datos de Secuencia Molecular , Conejos , Ratas , Ratas Sprague-Dawley , Alineación de Secuencia , Eliminación de Secuencia/genética , Estadísticas no Paramétricas , Vacunas Atenuadas/genética , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/farmacología , Vibrio cholerae O139/genéticaRESUMEN
Paracoccidioides brasiliensis is the fungus agent of paracoccidioidomycosis, a chronic systemic disease prevalent in Latin America. The aim of the present work was to evaluate the protection elicited by the immunization of BALB/c mice with radioattenuated yeast cells of P. brasiliensis. The immunization promoted a long lasting protection against highly infective yeast forms of P. brasiliensis. A 99.5% decrease in CFUs recovery was verified 90 days post challenge. At the same time the levels of IgG2a and IFN-gamma were high while a very low production of IL-10 and IL-5 was verified, suggesting that a Th1 pattern was dominant. This work shows the potential of radioattenuated yeast cells for the development of vaccines against fungi infections.
Asunto(s)
Vacunas Fúngicas/inmunología , Rayos gamma , Paracoccidioides/inmunología , Paracoccidioidomicosis/prevención & control , Animales , Vacunas Fúngicas/farmacología , Humanos , Inmunización , Inmunoglobulina G/inmunología , Interferón gamma/inmunología , Interleucina-10/inmunología , Interleucina-5/inmunología , América Latina , Ratones , Ratones Endogámicos BALB C , Paracoccidioides/patogenicidad , Paracoccidioidomicosis/inmunología , Células TH1/inmunología , Factores de Tiempo , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/farmacologíaRESUMEN
Previous observations demonstrated that the delivery of recombinant Salmonella enterica serovar Dublin strains to mice via mucosal routes did not efficiently activate systemic and secreted antibody responses to either type d flagellin or genetically fused heterologous B-cell epitopes, thus reducing the usefulness of the protein as a carrier of epitopes for vaccine purposes. In this work, we investigated murine systemic and mucosal flagellin immunogenicity after oral immunization with attenuated Salmonella strains. The reduced anti-type d flagellin antibody responses in mice immunized via mucosal routes with three doses of flagellated S. enterica serovar Dublin strains were not caused by oral tolerance and could not be restored by coadministration of a mucosal adjuvant. The induction of antibody responses to Salmonella flagellins was shown to differ according to the genetic background, but not the haplotype, of the mouse lineage. Moreover, BALB/c mice orally immunized with S. enterica serovar Typhimurium strains developed anti-type i flagellin sera and secreted antibody responses, which indicated that the serovar of the Salmonella vaccine strain also affected flagellin immunogenicity. Analyses of cytokine responses of BALB/c mice immunized with three oral doses of flagellated S. enterica serovar Dublin vaccine strains showed that, in spite of the lack of antibody responses, elevated type d flagellin-specific CD4-cell-activation-dependent gamma interferon (IFN-gamma) and interleukin-10 responses were elicited after the administration of the vaccine strains via either parenteral or mucosal routes. Similar cytokine production patterns were detected to a T-cell heterologous epitope, derived from the CFA/I fimbriae of enterotoxigenic Escherichia coli (ETEC), in mice orally immunized with a Salmonella vaccine strain expressing hybrid flagella. These results indicate that the immunogenicities of Salmonella flagellins can differ significantly, depending on the murine host and on the bacterial vector used, and demonstrate that the induction of CD4-cell-activation-dependent IFN-gamma production represents a major immune response triggered by flagellin and in-frame fused heterologous T-cell epitopes after the oral administration of recombinant S. enterica serovar Dublin vaccine strains.
Asunto(s)
Flagelina/inmunología , Vacunas contra la Salmonella/farmacología , Salmonella enterica/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Administración Oral , Animales , Citocinas/biosíntesis , Femenino , Tolerancia Inmunológica , Inmunidad Mucosa , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos , Vacunas contra la Salmonella/administración & dosificación , Vacunas contra la Salmonella/inmunología , Salmonella enterica/patogenicidad , Salmonella typhimurium/inmunología , Salmonella typhimurium/patogenicidad , Vacunas Atenuadas/inmunología , Vacunas Atenuadas/farmacologíaRESUMEN
An attenuated line of Leishmania mexicana (the L. mexicana H-line) has been established by culturing in vitro under gentamicin pressure. BALB/c mice infected with the L. mexicana H-line developed a CD4(+)Th1-like response, indicated by the cytokine profile of their splenocytes stimulated by L. mexicana wild-type (WT) promastigotes. This profile is sustained after these mice are challenged with L. mexicana WT. Control mice infected with L. mexicana WT alone developed a CD4(+)Th2-like cytokine profile. In mice immunized with L. mexicana H-line and then challenged with WT-line, were eliminated when immunizing H-line parasites persisted in the skin and draining popliteal lymph nodes (PLNs). In experiments in which mice were inoculated with attenuated and WT parasites at the same time, either at the same site or on separate sides of the mouse, growth of the WT parasites was significantly contained and controlled, indicating a possible therapeutic role for the attenuated parasites.
Asunto(s)
Gentamicinas/farmacología , Leishmania mexicana/efectos de los fármacos , Leishmania mexicana/inmunología , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/prevención & control , Células TH1/inmunología , Animales , Anticuerpos Antiprotozoarios/sangre , Citocinas/biosíntesis , Femenino , Inmunoglobulina G/sangre , Técnicas In Vitro , Leishmaniasis Cutánea/parasitología , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Vacunas Antiprotozoos/farmacología , Vacunas Atenuadas/farmacologíaRESUMEN
A candidate live-attenuated virus vaccine for protection against Venezuelan equine encephalitis (VEE) (designated V3526) was tested in mice to measure the magnitude, duration, and kinetics of virus replication in the blood and the central nervous system and its phenotypic stability after multiple passages in mice and cell culture. All results were compared to parallel experiments with parental virus and the existing VEE virus vaccine, TC-83. Maximum virus titers in the brains of V3526-inoculated mice were between 10- and 100-fold less than those observed in brains of mice inoculated intracranially (i.c.) with either the parental virus or TC-83. Neither V3526 nor TC-83 was lethal in BALB/c mice inoculated i.c.. However, mice inoculated with TC-83 developed acute symptoms lasting at least 14 days. In contrast, i.c. inoculation of TC-83 was uniformly lethal for C3H/HeN mice. V3526 was avirulent in both BALB/c and C3H/HeN mice after i.c. inoculation. The virulence characteristics of V3526 remained unchanged after five serial i.c. passages in mouse brains or after five cell culture passages. Finally, pathologic changes induced after i.c. inoculation of V3526 were consistently less severe and of shorter duration than those observed in TC-83-inoculated mice. Based on these results, V3526 is stable and appears to be significantly less neurovirulent in mice than TC-83.
Asunto(s)
Encéfalo/efectos de los fármacos , Virus de la Encefalitis Equina Venezolana/efectos de los fármacos , Encefalomielitis Equina Venezolana/prevención & control , Vacunas Virales/farmacología , Animales , Encéfalo/patología , Células Cultivadas/efectos de los fármacos , Hibridación in Situ , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Vacunas Atenuadas/farmacologíaRESUMEN
Two investigational vaccines, TC-83 (live-attenuated) and C-84 (formalin-inactivated), are currently available to immunize at-risk individuals against Venezuelan equine encephalitis virus (VEE). Ideally, such vaccines should protect against both the natural mosquito-borne route of infection and from aerosol, the most common route of laboratory infection. Whereas considerable data on vaccine efficacy following parenteral challenge are available, the efficacy of these vaccines against disease caused by aerosol exposure is not well established in primates. We compared the immunogenicity and protective capacity of TC-83 and C-84 against either subcutaneous or aerosol routes of infection in cynomolgus monkeys implanted with temperature-monitoring radiotelemetry devices. A single s.c. dose of TC-83, or three s.c. doses (days 0, 7, 28) of C-84, elicited similar serum virus-neutralizing antibody responses. Animals immunized with either TC-83 or C-84 were protected against s.c. infection. In contrast, after aerosol infection, 40% of the animals vaccinated with either TC-83 or C-84 developed signs nearly as severe as those seen in unvaccinated animals. Protection was not entirely consistent with the measured preinfection immune responses: unprotected animals had serum virus-neutralizing antibody titers and lymphoproliferative responses similar to those seen in protected animals. In this study, C-84 (three doses) protected monkeys as well as TC-83 (one dose) against either a s.c. or aerosol VEE challenge.