Antigen presentation in vaccine development

A variety of microorganisms, nutrients or toxins are generally intrude our body through mucosal tissues or skin, where equipment for both preventing their invasions and catching their information to activate internal immune systems for adapting surroundings is arranged. Among the equipment, cells in charge of innate immunity, particularly dendritic cells (DCs), having an excellent capacity for prompt recognition of invaded pathogens via toll-like receptors (TLRs) to alert B and T cells for establishing aquired/adaptive immunity by presenting their processed antigenic fragments, have been paid great attention. These TLR-activated, antigen captured DCs are divided into two groups; one is pathogen-retaining unit and the other is pathogen-controlling unit. The latter DCs present processed antigenic molecules from the pathogens to competent β T cells together with special containers, such as class I, class II MHC and CD1 to generate specific cellular immunity. The former two MHC molecules can present processed peptide antigens, whereas the last CD1 molecule can present glycolipid/lipid antigens. In contrast, B lymphocytes that captured antigens via their specific immunoglobulin (Ig) receptors present digested peptide fragments with their class II MHC to stimulate suitable CD4⁺ helper T cells which in turn secrete various cytokines to efficiently expand and maintain antibody production from that partner B cells to establish humoral immunity. These β T cells and antibodies, recognize either processed antigenic peptide or glycolipid fragments, and thus, identification of these epitopes enables us to generate artificial pathogen-specific vaccines. Based on the recent findings about precise mechanisms of antigen processing and presentation orchestrated at the surface compartment, future development of vaccines against various pathogens are discussed.     

Controle d'activite des vaccins antirabiques inactives. Problemes poses par l'utilisation du test de HabelPotency testing of veterinary vaccines containing inactivate virus. Difficulties raised by the use of Habel test

Le test de Habel utilisé dans le monde entier a rendu d'inestimables services. Il continuera à en rendre longtemps encore puisqu'il permet de caractériser de façon simple et rapide un très bon ou un très mauvais vaccin.

Grâce à une interprétation critique et raisonnée des résultats obtenus il est possible de distinguer des vaccins de valeur moyenne ou médiocre mais, dans ce cas, l'imprécision de ce test est grande, ce qui pose à l'expérimentateur des problèmes évidents.

En raison, d'une part de la nécessité d'utiliser un test aussi simple que le test de Habel, mais plus fiable, d'interprétation plus aisée et répondant mieux aux conditions d'utilisation des vaccins préventifs sur le terrain, et d'autre part, de la difficulté à généraliser actuellement tout au moins un test qui implique l'emploi d'un vaccin de référence, il nous semble possible et souhaitable de définir dès maintenant, en tenant compte des travaux antérieurs sur cette question, une technique qui réponde à ces impératifs.     

Experience gained in immunotherapy from the immunopharmacology of BCG leading to a second generation of systemic immunity adjuvants

Even after using the first arms against tumour (surgery and radiotherapy) 70% of solid tumours reappear. Chemotherapy cannot eliminate ‘the last cell’. Specific and/or non specific immunotherapy helps the organism to eliminate the last cells by stimulating its immune capacity.

The different generations of adjuvants, agents of immunotherapy were studied successively. BCG belongs to the first generation of adjuvants. We considered its association with specific immunotherapy (of irradiated tumour cells) and/or chemotherapy (cyclophosphamide), then we analysed the problems of dose and the ways of administration, advantages and disadvantages (stimulation of suppressor cells).

Second generation of adjuvant (Corynebacterium parvum, nucleotids and levamisole) allowed to specify the parameters of the efficiency of adjuvants. They have the same disadvantages as BCG.

Finally the third generation share the following characteristics: their side-effects will be minimal (they will not induce suppressor cells), their action will be limited to stimulate one population of cells only and they will be well defined chemical compounds. Thymosin, Bestatin and MDP belong to this generation. Combinations of adjuvants may also be envisaged with the objective of stimulating a particular mechanism of antitumoural activity.     

Powder and particle-mediated approaches for delivery of DNA and protein vaccines into the epidermis

The epidermis of the skin is both a sensitive immune organ and a practical target site for vaccine administration. However, administration of vaccines into the epidermis is difficult to achieve using conventional vaccine delivery methods employing a needle and syringe. A needle-free vaccine delivery system has been developed that efficiently delivers powdered or particulate DNA and protein vaccines into the epidermal tissue. The delivery system can be used to directly transfect antigen presenting cells (APCs) by formulating DNA or protein vaccines onto gold particles (particle-mediated immunization). Antigen can be directly presented to the immune system by the transfected APCs. Antigen can also be expressed and secreted by transfected keratinocytes and picked up by resident APCs through the exogenous antigen presentation pathway. Alternatively, protein antigens can be formulated into a powder and delivered into the extracellular environment where they are picked up by APCs (epidermal powder immunization). Using any of these formulations, epidermal immunization offers the advantage of efficiently delivering vaccines into the APC-rich epidermis. Recent studies demonstrate that epidermal vaccine delivery induces humoral, cellular, and protective immune responses against infectious diseases in both laboratory animals and man.     

Leishmaniasis: Report of 33 cases and a review of the literature

Leishmaniasis are parasitic diseases in extension. They appear in new foci, because of important displacements of populations, and they affect immunocompromised patients (under chemotherapy, transplanted, or HIV infected). Study of 33 cases of leishmaniasis, 22 visceral and 11 cutaneous, at the Hôpital du Kremlin-Bicêtre, France, showed predominant contamination in Maghreb and in the south of France. In the case of Kala-Azar, fever (18 cases) and hepatosplenomegaly (19 cases) are frequent, and the serodiagnosis and the search of parasites by myelogram are always positive. In HIV-infected individuals, clinical signs are similar, but the serodiagnosis is less reliable. Evolution is bad in transplanted patients who must remain under immunosuppressive drugs. In the case of cutaneous leishmaniasis, diagnosis is based on local sample, while the serodiagnosis remains negative. Treatment is sometimes long, necessitating repeated treatments.     

Induction and effector phases of the immune response: Physiological and pathophysiological features

A review is given on the current state of knowledge about the induction and effector phases of the immune response. Physiological and pathophysiological features of the regulation of the immune response are discussed comparatively for both man and animals.     

Avian toxoplasmosis: Experimental infection of chicken and pigeon

Two groups of 13 new-laying hens each were infected by crop-route with 5000 and 50,000 infective oocysts of T. gondii. Four groups of 5 pigeons each were inoculated by crop-route with 50, 500, 1000 and 5000 infective oocysts. To each group of infected birds suitable controls were added. Hens from the experiment with 5000 infective oocysts were apparently resistant to the infection and they had no clinical signs in the succeeding 40 days p.i. Hens from the experiment with 50,000 infective oocysts showed an egg-drop and mortality in embryonated eggs, especially during the first 2 weeks p.i. Isolation of the parasite was unsuccessfully attempted from 720 embryonated eggs, produced by infected groups, and tested on various days p.i. and at different stages of infection. The parasite was isolated from the brain, heart, liver, spleen and lung of infected birds 7 and 15 days p.i.; 40 days p.i. it was evident only in brain and heart. IgG onset and mean course were monitored by ELISA and high titers were reached by both groups. Pigeons from groups 500, 1000 and 5000 developed rapidly progressive clinical signs as diarrhea, trembling, incoordination, torcicollis and death. They had enlargement of liver and spleen and focal necrosis, nodular features in the crop. Pigeons from expt 50 had no clinical signs in spite of the presence of the parasite in their organs for over 45 days p.i. Parasite was isolated from brain, heart, liver, spleen, lung, kidney, crop and muscles from all infected groups. Histopathological and ultrastructural features revealed the presence of multiplying tachizoites even within cells of the crop. Seroconversion, as monitored by ELISA, was recorded in all infected groups although high ELISA-titres were never reached. One of the negative controls from expt 5000 developed specific antibodies but the parasite was not isolated from its organs.     

Role of the international organisation for animal health (Office International des Epizooties: OIE) in the control of foot and mouth disease

The author describes activities conducted by the International Organisation for Animal Health (OIE: Office International des Epizooties) to control foot and mouth disease (FMD) world-wide. These activities fall within the framework of the principal missions of the OIE.

The first of these missions is the collection and dissemination of epidemiological information and of scientific knowledge on animal diseases, the socio-economic or disease implications of which can be particularly serious. The implementation of the measures required to control the disease and to protect countries threatened by FMD depends on the quality and rapidity of the transmission of this information.

The co-ordination of studies, research and control programmes against FMD is equally important for the OIE. This work is based, in particular, on work conducted by the OIE foot and mouth disease and other epizootics Commission. OIE Member Countries not only have access to the most recent data on the diagnosis, surveillance and control of FMD but also have recourse to the official recognition procedure for disease-free status provided by this Commission.

Finally, through the standardisation of health recommendations, diagnostic tests, manufacture protocols and the control of biological products, made available by the OIE International Animal Health Code Commission in regard to the former and by the OIE Standards Commission in regard to the latter, the OIE provides the reference for international trade in animals and animal products, and is recognised in this role by the World Trade Organization.

Résumé

L'auteur décrit les actions conduites par l'Office international des épizootie (OIE) pour lutter contre la fièvre aphteuse dans le monde entire. Ces actions figurent parmi les principales missions de l'OIE.

La première de ces missions est la collecte et la diffusion d'informations épidémiologiques ainsi que des connaissances scientifiques sur les maladies animales qui peuvent avoir des répercussions socio-économiques particulièrement importantes. L'amélioration des mesures nécessaires pour lutter contre la maladie et pour protéger les pays menacés par la fièvre aphteuse dépend de la qualité et de la rapidité de transmission de ces informations.

La coordination d’études, de recherches et de programmes de lutte contre la fièvre aphteuse est également importante pour I'OIE. Ce travail repose en particulier sur celui de la Commission de I'O.I.E sur la fièvre aphteuse et les autres épizooties. Non seulement les Pays Membres de l'OIE ont accès aux données les plus récentes sur le diagnostic, la surveillance et la lutte contre la fièvre aphteuse, mais ils bénéficient aussi de la procédure de reconnaissance officielle du statut de zone indemne gérée par cette Commission.

Enfin, à travers la standardisation des recommendations sanitaires, des tests de diagnostic, des protocoles de fabrication et du contrôle des produits biologiques réalisée par la Commission OIE du Code zoosanitaire et par la Commission OIE des normes, l'OIE constitue la référence pour le commerce international des animaux et des produits animaux, et il est reconnu dans ce rôle par I'OMC.     

Detection of rotavirus in faecal specimens with a monoclonal antibody enzyme-linked immunosorbent assay: Comparison with polyclonal antibody enzyme immuno-assays and a latex agglutination test

Monoclonal antibodies have been produced against the 81/36F strain of rotavirus. One of them, was chosen as diagnostic reagent: it showed high ELISA reactivity with all the bovine, human and porcine rotavirus strains tested and reacted with VP6, structural protein product known to support the common rotavirus antigen.

A sandwich ELISA procedure using the chosen monoclonal as “capture and detecting” antibody was performed to detect rotavirus in faecal samples from experimentally inoculated newborn calves: it always gave a negative response with meconium and a positive response for the stool specimens which rotavirus have been isolated. This assay was compared with Enzygnost and Slidex Rota Kit tests and with a non-commercial sandwich ELISA test using polyclonal antibodies: it showed more sensitivity than the agglutination test and was as sensitive as the other two tests to detect rotavirus in routine diagnostic material. The test evaluated showed no equivocal results.     

Action of FAO in the control of foot and mouth disease

This paper describes the role played by FAO in the control of foot and mouth disease. Since 1954 the FAO European Commission for the control of foot-and-mouth disease co-ordinated the regional programme for eradication of FMD in Europe. One of the major achievements of the Commission has been to prevent the introduction and spread of exotic strains of foot and mouth disease into Europe through the Balkans. FAO also supports the activities of the Foot-and-Mouth Disease World Reference Laboratory located in the Institute of Animal Health, Pirbright, UK.

The Infectious Diseases/EMPRES Group of the Animal Health Service, Animal Production and Health Division of FAO, promotes a global approach to the control and eradication of transboundary animal diseases over the world. For foot and mouth disease, the strategy is based on co-ordinated regional programmes. For FAO, no sustainable progress can be achieved in FMD control over the world without addressing and supporting the control of the disease in endemic countries.

Résumé

L'article décrit le rôle joué par la FAO dans la lutte contre la fièvre aphteuse. Depuis 1954, la Commission Européenne de Lutte contre la fièvre aphteuse de la FAO coordonne le programme régional d’éradication en Europe. Un des succès majeur de cette Commission a été de prévenir l'introduction et la diffusion des souches exotiques de virus de la fièvre aphteuse à travers les Balkans. La FAO soutient également les activités du Laboratoire Mondial de référence pour la fièvre aphteuse qui se situe à l'Institut pour la Santé Animale de Pirbright au Royaume Uni.

Le Groupe Maladies Infectieuses/EMPRES du Service de Santé Animale au sein de la Division Production et Santé Animale de la FAO défend une approche globale de lutte et d’éradication des maladies transfrontalières à travers le monde. Pour la fièvre aphteuse, la stratégie est basée sur une approche régionale coordonnée. Pour la FAO, aucun progres significatif durable ne peut être obtenu dans la lutte contre la fièvre aphteuse à travers le monde sans que la question de la lutte dans les pays où la maladie est endémique ne soit prise en compte et soutenue.