La presente invention a pour objet une composition destinee a inhiber une reponse immunitaire inf... more La presente invention a pour objet une composition destinee a inhiber une reponse immunitaire inflammatoire impliquant les composants d’excretion/ secretoires (ES) de Fasciola hepatica ou une fraction d’entre eux. La composition est particulierement utile dans le traitement ou la prophylaxie des reponses immunitaires inflammatoires induites par les lymphocytes T, notamment les maladies auto-immunes. L’invention concerne egalement des procedes de modulation d’une reponse immunitaire induite par les lymphocytes T comportant l’administration d’une quantite efficace therapeutiquement de composant d’excretion/ secretoire de Fasciola hepatica a un sujet necessitant un tel traitement pour inhiber le developpement de la reponse immunitaire.
Most vaccines used for humans work through humoral immunity, yet many appear to be protective eve... more Most vaccines used for humans work through humoral immunity, yet many appear to be protective even after specific circulating antibody levels have waned to undetectable levels. Furthermore, it has been difficult to define a serologic correlate of protection against a number of infectious diseases, including those caused by Bordetella pertussis. B. pertussis clearance in immunized mice has been shown to correlate with pertussis vaccine efficacy in children. This murine respiratory challenge model was used to demonstrate persistent vaccine-induced protection against B. pertussis in the absence of circulating antibody at the time of challenge. Whole-cell and acellular pertussis vaccines induced persistent memory T and B cells and anamnestic antibody responses after challenge. The findings suggest that immunologic memory is more significant in protection than is the induction of immediate antibody responses and imply that vaccinated children still may be protected against disease follow...
The evaluation of vaccines for human use requires reliable models of infection, that are predicti... more The evaluation of vaccines for human use requires reliable models of infection, that are predictive of protective efficacy. Traditionally whole cell pertussis vaccines (Pw) have been controlled using the Kendrick test, which measures protection following intracerebral challenge with Bordetella pertussis. However, this test is unsuitable for assessing the potency o f the new acellular pertussis vaccines (Pa). In this study, it was demonstrated that protection in a murine respiratory challenge model correlates with the protective efficacy of Pa and Pw in children, but vaccine potency could not be predicted on the basis of antibody responses against individual antigens. Furthermore, the murine model was shown to be a reliable method for the determination of consistency between different batches o f Pa and Pw. This study highlights the possible applications of the murine model in the regulatory control and future development of pertussis vaccines. The murine model of infection has been ...
The evaluation of vaccines for human use usually requires the development of appropriate animal m... more The evaluation of vaccines for human use usually requires the development of appropriate animal models and the definition of laboratory correlates of immunity. Traditionally whole cell pertussis vaccines have been controlled by using an active mouse protection test, which measures protection following intracerebral challenge with Bordetella pertussis. However, this test is unsuitable for assessing the potency of the new generation acellular pertussis vaccines. In the present study we demonstrate that a murine respiratory challenge model for infection with B. pertussis is suitable for assessing the potency of acellular and whole cell pertussis vaccines. To allow standardization of different vaccines we have expressed the area under the clearance curve for immunized mice as a ratio of that for non-immunized controls to obtain a potency index. A comparison of estimated vaccine efficacy in children with potency in the murine model results in a highly significant correlation (r = 0.976, p < 0.001). Furthermore, we have used this model to define the protective mechanism of immunity against respiratory infection with B. pertussis and demonstrate a requirement for both specific T and B cells. In accordance with studies in humans, no clear relationship was observed between monotypic serum antibody responses against the putative protective antigens of B. pertussis and protection. In contrast, the most potent protection was observed when the T cell response is polarized to the Th1 subtype.
La presente invention a pour objet une composition destinee a inhiber une reponse immunitaire inf... more La presente invention a pour objet une composition destinee a inhiber une reponse immunitaire inflammatoire impliquant les composants d’excretion/ secretoires (ES) de Fasciola hepatica ou une fraction d’entre eux. La composition est particulierement utile dans le traitement ou la prophylaxie des reponses immunitaires inflammatoires induites par les lymphocytes T, notamment les maladies auto-immunes. L’invention concerne egalement des procedes de modulation d’une reponse immunitaire induite par les lymphocytes T comportant l’administration d’une quantite efficace therapeutiquement de composant d’excretion/ secretoire de Fasciola hepatica a un sujet necessitant un tel traitement pour inhiber le developpement de la reponse immunitaire.
Most vaccines used for humans work through humoral immunity, yet many appear to be protective eve... more Most vaccines used for humans work through humoral immunity, yet many appear to be protective even after specific circulating antibody levels have waned to undetectable levels. Furthermore, it has been difficult to define a serologic correlate of protection against a number of infectious diseases, including those caused by Bordetella pertussis. B. pertussis clearance in immunized mice has been shown to correlate with pertussis vaccine efficacy in children. This murine respiratory challenge model was used to demonstrate persistent vaccine-induced protection against B. pertussis in the absence of circulating antibody at the time of challenge. Whole-cell and acellular pertussis vaccines induced persistent memory T and B cells and anamnestic antibody responses after challenge. The findings suggest that immunologic memory is more significant in protection than is the induction of immediate antibody responses and imply that vaccinated children still may be protected against disease follow...
The evaluation of vaccines for human use requires reliable models of infection, that are predicti... more The evaluation of vaccines for human use requires reliable models of infection, that are predictive of protective efficacy. Traditionally whole cell pertussis vaccines (Pw) have been controlled using the Kendrick test, which measures protection following intracerebral challenge with Bordetella pertussis. However, this test is unsuitable for assessing the potency o f the new acellular pertussis vaccines (Pa). In this study, it was demonstrated that protection in a murine respiratory challenge model correlates with the protective efficacy of Pa and Pw in children, but vaccine potency could not be predicted on the basis of antibody responses against individual antigens. Furthermore, the murine model was shown to be a reliable method for the determination of consistency between different batches o f Pa and Pw. This study highlights the possible applications of the murine model in the regulatory control and future development of pertussis vaccines. The murine model of infection has been ...
The evaluation of vaccines for human use usually requires the development of appropriate animal m... more The evaluation of vaccines for human use usually requires the development of appropriate animal models and the definition of laboratory correlates of immunity. Traditionally whole cell pertussis vaccines have been controlled by using an active mouse protection test, which measures protection following intracerebral challenge with Bordetella pertussis. However, this test is unsuitable for assessing the potency of the new generation acellular pertussis vaccines. In the present study we demonstrate that a murine respiratory challenge model for infection with B. pertussis is suitable for assessing the potency of acellular and whole cell pertussis vaccines. To allow standardization of different vaccines we have expressed the area under the clearance curve for immunized mice as a ratio of that for non-immunized controls to obtain a potency index. A comparison of estimated vaccine efficacy in children with potency in the murine model results in a highly significant correlation (r = 0.976, p < 0.001). Furthermore, we have used this model to define the protective mechanism of immunity against respiratory infection with B. pertussis and demonstrate a requirement for both specific T and B cells. In accordance with studies in humans, no clear relationship was observed between monotypic serum antibody responses against the putative protective antigens of B. pertussis and protection. In contrast, the most potent protection was observed when the T cell response is polarized to the Th1 subtype.
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Papers by Miriam Brady