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1.
Vaccine ; 27(40): 5496-504, 2009 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-19632316

RESUMEN

Infection of rabbits with aerosolized rabbitpox virus (RPXV) produces a disease similar to monkeypox and smallpox in humans and provides a valuable, informative model system to test medical countermeasures against orthopoxviruses. Due to the eradication of smallpox, the evaluation of the efficacy of new-generation smallpox vaccines depends on relevant well-developed animal studies for vaccine licensure. In this study, we tested the efficacy of IMVAMUNE [modified vaccinia Ankara-Bavarian Nordic (MVA-BN)] for protecting rabbits against aerosolized RPXV. Rabbits were vaccinated with either phosphate-buffered saline (PBS), Dryvax, a single low dose of IMVAMUNE, a single high dose of IMVAMUNE, or twice with a high dose of IMVAMUNE. Aerosol challenge with a lethal dose of RPXV was performed 4 weeks after the last vaccination. All PBS control animals succumbed to the disease or were euthanized because of the disease within 7 days postexposure. The rabbits vaccinated with Dryvax, a low dose of IMVAMUNE, or a single high dose of IMVAMUNE showed minimal to moderate clinical signs of the disease, but all survived the challenge. The only clinical sign displayed by rabbits that had been vaccinated twice with a high dose of IMVAMUNE was mild transient anorexia in just two out of eight rabbits. This study shows that IMVAMUNE can be a very effective vaccine against aerosolized RPXV.


Asunto(s)
Vacuna contra Viruela/inmunología , Virus Vaccinia/inmunología , Vaccinia/prevención & control , Animales , Anticuerpos Antivirales/sangre , Línea Celular , Chlorocebus aethiops , Ensayo de Inmunoadsorción Enzimática , Femenino , Pruebas de Neutralización , Conejos , Vacunas Atenuadas/inmunología , Vaccinia/inmunología , Carga Viral , Ensayo de Placa Viral
2.
J Virol ; 79(12): 7845-51, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15919938

RESUMEN

The use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naive and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and immunocompromised animals, and its efficacy against smallpox is currently being addressed. Here we directly compare the efficacies of MVA alone and in combination with classical VV-based vaccines in a cynomolgus macaque monkeypox model. The MVA-based smallpox vaccine protected macaques against a lethal respiratory challenge with monkeypox virus and is therefore an important candidate for the protection of humans against smallpox.


Asunto(s)
Monkeypox virus/patogenicidad , Mpox/prevención & control , Infecciones del Sistema Respiratorio/prevención & control , Vacuna contra Viruela/inmunología , Virus Vaccinia/inmunología , Animales , Anticuerpos Antivirales/sangre , Modelos Animales de Enfermedad , Humanos , Inmunización , Pulmón/patología , Pulmón/virología , Macaca fascicularis , Mpox/patología , Mpox/virología , Monkeypox virus/inmunología , Infecciones del Sistema Respiratorio/patología , Infecciones del Sistema Respiratorio/virología , Piel/patología , Piel/virología , Vacuna contra Viruela/administración & dosificación , Linfocitos T/inmunología , Virus Vaccinia/genética
3.
Vet Immunol Immunopathol ; 90(1-2): 55-63, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12406655

RESUMEN

DNA vaccination, delivered through various routes, has been used extensively in laboratory animals. Few studies have focused on veterinary species and while results obtained in laboratory animals can often be extrapolated to veterinary species this is not always the case. In this study we have compared the effect of the route of immunisation with DNA on the induction of immune responses and protection of sheep to challenge with live Corynebacterium pseudotuberculosis. Intramuscular injection of plasmid DNA encoding an inactivated form of the phospholipase D (PLD) antigen linked to CTLA4-Ig resulted in the induction of a strong memory response and sterile immunity following challenge in 45% of the animals. In contrast, gene gun delivery or subcutaneous (SC) injection of the DNA vaccine induced comparatively poor responses and insignificant levels of protection. Thus, DNA vaccine efficacy in sheep is strongly influenced by the route of vaccination. Amongst intramuscular vaccinates, protected sheep had significantly elevated IgG2 responses compared to unprotected animals, while both subgroups had equivalent IgG1 levels. This suggests that the presence of IgG2 antibodies and hence a Th1-like response, induced by the DNA vaccine gave rise to protective immunity against C. pseudotuberculosis.


Asunto(s)
Infecciones por Corynebacterium/inmunología , Infecciones por Corynebacterium/prevención & control , Enfermedades de las Ovejas/prevención & control , Oveja Doméstica/inmunología , Vacunación/veterinaria , Vacunas de ADN/administración & dosificación , Vacunas de ADN/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/inmunología , Biolística , Corynebacterium pseudotuberculosis/inmunología , Memoria Inmunológica , Inyecciones Intramusculares , Inyecciones Subcutáneas , Enfermedades de las Ovejas/inmunología
4.
Infect Immun ; 70(4): 1949-56, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11895958

RESUMEN

More effective vaccines against Mycobacterium tuberculosis may contribute to the control of this major human pathogen. DNA vaccines encoding single mycobacterial proteins stimulate antimycobacterial T-cell responses and induce partial protection against M. tuberculosis in animal models. The protective efficacy of these vaccines encoding a single antigen, however, has been less than that afforded by the current vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG). The heterodimeric cytokine interleukin-12 (IL-12) potentiates the induction and maintenance of the type 1 helper T-cell response. We have developed a novel self-splicing vector based on the 2A protein of foot-and-mouth disease virus that permits the coordinate expression of both chains of IL-12 (p2AIL12). Coimmunization with this vector and DNA expressing M. tuberculosis antigen 85B or MPT64 enhanced the specific lymphocyte proliferative response and increased the frequency of specific gamma interferon-secreting T cells against the whole protein and a defined CD8(+) T-cell epitope on MPT64. Further, coimmunizing with p2AIL12 significantly increased the protective efficacy of DNA-85 in the lung against an aerosol challenge with M. tuberculosis to the level achieved with BCG. Therefore, codelivery of an IL-12-secreting plasmid may be a potent strategy for enhancing the protective efficacy of vaccines against M. tuberculosis.


Asunto(s)
Vacuna BCG/inmunología , Interleucina-12/genética , Vacunas de ADN/inmunología , Vacunas Sintéticas/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Femenino , Vectores Genéticos , Interleucina-12/inmunología , Ratones , Ratones Endogámicos C57BL , Linfocitos T/inmunología , Proteínas Virales/inmunología
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