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At least 505 records · Page 28Linked to original sources

PubMed2004

The immunology of Leishmania infection and the implications for vaccine development.

Leishmania parasites are vector-borne protozoal pathogens found in tropical and subtropical regions of both the Old and New World. These parasites can cause visceral or cutaneous disease, and the pathology of the infection is determined by both host immune factors and species/strain differences of the parasite. Dogs are an important reservoir for maintaining the population of Leishmania parasites that can lead to visceral leishmaniasis in humans, and a vaccination approach may be an effective method for reducing the numbers of infected dogs. Resistance to leishmaniasis has been consistently associated with a T helper 1 immune response, characterized by the production of IFN-gamma by the antigen-specific lymphocyte population. The development of this Th1 response has been shown to be dependent upon both cytokines and dendritic cells during T cell activation. However, the development of a Leishmania vaccine effective in preventing these chronic diseases has proven to be a challenge. Vaccine trials have focused on whole-killed or subunit vaccines with adjuvants. Newer experimental strategies involve the attenuation of the Leishmania parasite via gene deletion technologies or the expression of specific Leishmania peptides within attenuated organisms, such as Bacillus Calmette Guérin. DNA vaccines and dendritic cell potentiators, such as CpG oligodeoxynucleotides and Flt-3 ligand, are also in the early stage of development. In addition, as part of blocking the transmission cycle of leishmaniasis, several laboratories are also exploring the possibility of immunomodulating the host toward the bite of the sand fly.

Animals↗

PubMed2002

The status of HPV16-specific T-cell reactivity in health and disease as a guide to HPV vaccine development.

Human papilloma viruses (HPV) are among the most common sexually transmitted pathogens in young adults. In the majority of individuals, anti-viral immunity is capable of suppressing viral infection but in a minority of patients viral infection is not cleared in time to prevent the development of malignancies. In these cases, HPV16-specific immunity may develop too late, is not strong enough, and/or is possibly of the wrong type. The influence of pre-existing immunity on the efficacy of vaccines is largely unknown. Nor has it been studied what the effect is of vaccines on the various types of pre-existing HPV-specific T-cell immunity. Animal models showing that vaccines are able to protect against a subsequent tumor challenge and even to treat transplantable tumors, are not qualified to address this point because tumor development is not preceded by persistent viral infection. Therefore, the comparison between fully characterized pre-existing HPV-specific immunity in patients and healthy subjects is a prerequisite for the full appreciation of vaccine-efficacy as well as for further development of next-generation vaccines.

Drug Design↗

PubMed1988

Role of non-human primates in malaria vaccine development: memorandum from a WHO meeting.

This Memorandum discusses the coordination and standardization of malaria vaccine research in non-human primates to encourage optimum use of the available animals in experiments that are fully justified both scientifically and ethically. The requirements for experimentation in non-human primates, the availability of suitable animals for malaria vaccine studies, and the criteria for testing candidate vaccines are considered. The policy and legislation relevant to the use of non-human primates in biomedical research are also briefly discussed. The Memorandum concludes with eight recommendations.

Animal Welfare↗

PubMed1997

Bacterial ADP-ribosylating toxins: form, function, and recombinant vaccine development.

No products of the biotechnology revolution will likely have a greater legacy than recombinant vaccines. Clinical efficacy trials of new acellular pertussis vaccines have recently been completed; among them, a vaccine containing a genetically modified pertussis toxin showed superior effectiveness in protection against disease caused by Bordetella pertussis. The foundations for this vaccine derive from the work of many investigators, but most notably: Japanese researchers who demonstrated the potential for subcomponents of B. pertussis, and particularly pertussis toxin, to confer protective immunity; research teams in Italy and the United States who cloned and sequenced the pertussis toxin operon; and our own group who molecularly dissected the toxin molecule to produce recombinant analogs of this heterohexameric protein that retained protective immunogenicity yet lacked the intrinsic enzyme activity that results in the adverse reactogenic effects of immunization. Another result of the research leading to this new pertussis vaccine is an intimate understanding of the relationship between form and function in the ADP-ribosylating toxins with AB5 architecture, including the structure of their catalytic domains their immunologic and adjuvant properties, characteristics and possible pathologic consequences of host cell receptor recognition, and the assembly and subunit interactions of these complex multimeric proteins.

Adenosine Diphosphate Ribose↗

PubMed2002

Vaccine development using the simian immunodeficiency virus model for AIDS.

OBJECTIVE: A number of trials in primates using a wide range of putative vaccines based on simian immunodeficiency virus (SIV) have been performed and are summarised here. METHODS: Rhesus macaques and African green monkey (AGMs) were immunised with the test vaccines and challenged with live virus to test the efficacy of the induced or transferred immune responses to protect from infection or disease development. RESULTS: In initial studies, successful protection from challenge by whole inactivated virus vaccines was subsequently shown to be mediated by immune responses to human cell rather than viral proteins. Passive transfer of neutralising antibodies failed to protect against challenge. The induction of SIV-specific cytotoxic T lymphocytes (CTLs) using lipopeptides also failed to protect from infection, and whereas the frequency of post-infection CTLs (as measured by limiting dilution CTL assay and MHC/tetramer staining) correlated inversely with the cell-associated virus load, no correlation with the plasma virus load was observed. No immunological correlation of protection could be identified in macaques immunised with live attenuated SIV, with sterilising immunity being induced as early as 10 weeks after infection with the attenuated virus. Similarly, whole inactivated virus and passive IgG transfer failed to protect the natural host AGM species from challenge with apathogenic SIVagm, although live attenuated SIVagm afforded some protection despite the lack of overt vaccine virus replication. CONCLUSIONS: 'Traditional' types of vaccine are either ineffective or inappropriate for use in humans. Current efforts are therefore focusing on the rapidly evolving field of genetic vaccines based on vector DNA and recombinant, attenuated viral and bacterial vectors.

Animals↗

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