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At least 397 records · Page 22Linked to original sources
PubMed1998

Detection of antibodies to Neospora caninum in bovine postabortion blood samples from Hungary.

In order to obtain data on the occurrence of the protozoan parasite Neospora caninum as a potential factor in the aetiology of reproduction problems in cattle, 97 postabortion sera were examined by ISCOM ELISA and IFAT for the presence of antibodies in N. caninum. The results showed 10% and 9% seropositivity by the ELISA and IFAT, respectively. In 2 of the 10 seropositive cases no other fetopathogenic agents (such as Chlamydia sp., Leptospira spp. or bovine viral diarrhoea virus) were detected. These data confirm the presence of N. caninum in cattle in Hungary.

Abortion, Veterinary↗
PubMed1995

Crossrecognition by CD8 T cell receptor alpha beta cytotoxic T lymphocytes of peptides in the self and the mycobacterial hsp60 which share intermediate sequence homology.

Immunization of C57BL/6 mice with the mycobacterial heat shock protein (hsp) 60 in immunostimulating complexes caused the in vivo activation of autoreactive major histocompatibility complex class I (H-2Db)-restricted CD8 T cell receptor (TcR) alpha/beta cells. A CD8 TcR alpha/beta clone with specificity for the mycobacterial hsp60 peptide499-508 was derived from this immunization, which, in addition, recognized syngeneic macrophages which had been stressed by interferon-gamma (IFN-gamma) stimulation. The stress-induced, self peptide could be extracted from IFN-gamma-stressed macrophages by acid elution, suggesting that the IFN-gamma-induced self peptide is derived from an endogenous protein. Based on our observation that lysis of stressed target cells by this cytotoxic T lymphocyte (CTL) clone was specifically inhibited by hsp60-specific antisense oligonucleotides, we used synthetic peptides representing amino acid (aa) sequences of the murine hsp60 for target cell sensitization and identification of the relevant self peptide. Synthetic peptides representing 9-mer to 11-mer aa sequences of the murine hsp60 with asparagine in anchor position 4 or 5 as the minimal requirement for H-2Db binding were tested in CTL assays. The overlapping murine hsp60 peptides162-170/171 were stimulatory at a concentration as low as 10-100 pM. Seven other peptides of the murine hsp60 required intermediate peptide concentrations of 10-100 nM for recognition by the CTL clone. Although the murine and mycobacterial hsp60 peptides recognized by this CTL clone showed only intermediate homology (3 identical and 3 similar aa), our data suggest that endogenous hsp60 itself is the source of self peptide(s) presented by IFN-gamma-stressed macrophages to the cross-reactive CTL clone with promiscuous specificity. This notion is consistent with the idea of hsp as a link between infection and autoimmunity.

Amino Acid Sequence↗
PubMed1998

Enhanced antibody and cytokine responses to influenza viral antigens in perforin-deficient mice.

Cytotoxic T lymphocytes (CTL) lyse virus-infected target cells by secreting the pore-forming effector molecule, perforin. Perforin-mediated cell death appears to be a major mechanism in viral clearance but its role in regulating immune responses in vivo is unclear. In this report, we show that following immunization with influenza viral antigens, perforin-deficient mice generated about 100-fold greater serum antibody responses than wild-type mice. Further, immune spleen cells from perforin knock-out mice secreted over 10-fold more IFN-gamma following in vitro restimulation than immune spleen cells from control mice. Finally, there were over 10-fold more IFN-gamma-secreting cells in cultures from perforin-deficient mice than those from control mice, suggesting that the enhanced cytokine release by T cells from perforin-deficient mice is due to an increase in the effector cell pool. Collectively, these results suggest that perforin-mediated effector function is required in the down-regulation of the immune response by way of limiting antigen-presenting cell function.

Animals↗
PubMed1993

A new immunostimulatory complex (PICKCa) in experimental rabies: antiviral and adjuvant effects.

The activity of an immunostimulatory complex (PICKCa) which is widely used against several human diseases in China was tested in experimental rabies prophylaxis. PICKCa protected mice against peripheral infection with both fixed and wild rabies strains. It also enhanced the protective activity of an experimental rabies vaccine injected either before or after rabies infection. PICKCa enhanced both non-specific immune responses and specific immunity including antibody production and cell mediated immunity as assessed by interleukin-2 production.

Adjuvants, Immunologic↗
PubMed2001

Biochemical and antigenic characterisation of Mycoplasma gallisepticum membrane proteins P52 and P67 (pMGA).

Two membrane proteins from the avian pathogen Mycoplasma gallisepticum have been previously purified using a simple, efficient and non-denaturing method: a lipoprotein P67 (pMGA) and P52. In the current study, the lipid part of P67 was chemically analysed. The molecular structure of the lipoprotein-lipid component was determined to be S-glyceryl cysteine with two O-ester-linked acyl chains. Fatty acid analysis of the purified P67 indicated a heterogeneous composition: palmitic acid (16:0)>stearic acid (18:0)>oleic acid (18:1c)>myristic acid (14:0), with 16:0 as the major component. These findings, along with previously published results, support the conclusion that P67 is pMGA1.2, a true membrane-associated lipoprotein although not N-acylated. In contrast to P67, P52 is not a lipoprotein. Topological experiments using in situ treatment with proteases and growth inhibition in the presence of anti-P52 serum provided evidence of the surface exposition of the polypeptide. The N-terminal sequence of P52 was found to be similar to the dihydrolipoamide acetyltransferase from several mollicutes; this enzyme is a membrane-associated component of the pyruvate dehydrogenase complex. Immunoblotting techniques revealed that the surface antigens P52 and P67 were specific to the species M. gallisepticum and the closely related species M. imitans. No antigenic difference was revealed within these species with the anti-P52 serum, while anti-P67 serum confirmed the antigenic variability of P67. The potential of P52 and P67 as antigens in serological diagnosis tests or as candidates for anti-mycoplasma subunit vaccines is discussed.

Amino Acid Sequence↗
PubMed2002

Immunostimulatory activity of cationic-lipid-nucleic-acid complexes against cancer.

Recent studies have highlighted the immunostimulatory nature of nucleic acids and the enhancement of such immunostimulation when nucleic acids are complexed to cationic liposomes to form cationic-lipid-nucleic-acid-complexes or lipoplexes. While such immunostimulation may have deleterious consequences for nucleic acid delivery, especially in the field of gene therapy, it may be harnessed for efficacious usage against the various forms of cancer.

Cations↗
PubMed1994

An update on approaches to the development of respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) vaccines.

RSV and PIV3 are responsible for about 30% of severe viral respiratory tract disease leading to hospitalization of infants and children. For this reason, there is a need to develop vaccines effective against these viruses. Since these viruses cause severe disease in early infancy, vaccines must be effective in the presence of maternal antibody. Currently, several strategies for immunization against these viruses are being explored including peptide vaccines, subunit vaccines, vectored vaccines (e.g., vaccinia-RSV or adenovirus-RSV recombinants), and live attenuated virus vaccines. The current status of these approaches is reviewed. In addition, the immunologic basis for the disease potentiation seen in vaccinees immunized with formalin-inactivated RSV during subsequent RSV infection is reviewed. The efficacy of immunization in the presence of maternal antibody is discussed. Much progress for a RSV and PIV3 vaccine has been made and successful immunization against each of these pathogens should be achieved within this decade.

Adult↗
PubMed2005

Exploiting receptor biology for oral vaccination with biodegradable particulates.

The effective delivery of antigens via the oral route is an extremely desirable goal. Mucosal delivery of antigens stimulates mucosal and systemic immunity without affecting maternal antibodies and reduces the need for sterile needles or trained personnel. To date, there are very few commercially available oral vaccines and despite numerous reports in the scientific literature to show the success of biodegradable antigen carriers, none of these have achieved commercial status. Nevertheless, many studies have shown the great potential of biodegradable antigen carriers for oral vaccination in preclinical studies, but a more rational approach may be to specifically target antigen-loaded biodegradable microspheres to cells in the mucosal immune system which transport and process antigens for T cell recognition. Modern cell and molecular biology techniques have unearthed a wealth of information regarding important receptors involved in the capture of luminal antigens by microfold or membranous (M) cells and receptors on dendritic cells (DCs) which may allow future targeting of antigens to specific DC phenotypes, thus directing the immune response appropriately. In this review, we consider the use of currently available biodegradable antigen carriers and speculate on how these may be improved to more efficiently target mucosal effector sites.

Administration, Oral↗
PubMed2006

CD28 and ICOS: similar or separate costimulators of T cells?

Numerous studies have revealed that the B7.1/B7.2-CD28 and B7RP-1-ICOS (Inducible COStimulator) pathways provide crucial costimulatory signals to T cells. We have compared the contribution of these pathways during primary and effector responses, in vitro and in vivo, molecularly as well as functionally. This comparison between CD28 an ICOS after initiation of T cell activation demonstrates that both CD28 and ICOS function similarly during expansion, survival and differentiation of T cells and that both CD28 and ICOS are necessary for proper IgG responses. The major differences between CD28 and ICOS are differences in expression of both receptors and ligands, and the fact that CD28 induces IL-2 production, whereas ICOS does not. In addition, ICOS is more potent in the induction of IL-10 production, a cytokine important for suppressive function of T regulatory cells. All data available at present indicate that both molecules are very suitable candidates for immunotherapy, each in their own unique way.

Animals↗
PubMed2004

Association of antigens to ISCOMATRIX adjuvant using metal chelation leads to improved CTL responses.

The association of antigen with ISCOMATRIX trade mark adjuvant has been shown to be important for the optimal induction of cytotoxic T lymphocyte (CTL) responses. Here, we describe a simple broadly applicable method for associating recombinant proteins with hexa-histidine tags to ISCOMATRIX trade mark adjuvant utilising metal-affinity chelating interactions. The metal chelation binding step can be performed in a wide range of buffers, including commonly used denaturants such as urea, which makes it an ideal strategy for formulating proteins which are otherwise insoluble. Following association of protein with the chelating ISCOMATRIX trade mark adjuvant, the denaturant can be removed. Further, we show enhanced CTL responses with a protein-associated chelating ISCOMATRIX trade mark vaccine compared to a non-associated ISCOMATRIX trade mark vaccine.

Adjuvants, Immunologic↗
PubMed2006

Particulate delivery systems for animal vaccines.

The requirements for veterinary vaccines are different to those of human vaccines. Indeed, while more side effects can be tolerated in animals than in humans; there are stricter requirements in terms of cost, ease of delivery (including to wildlife), and a need to develop vaccines in species for which relatively little is known in terms of molecular immunology. By their nature particulate vaccine delivery systems are well suited to address these challenges. Here, we review particulate vaccine delivery systems, ranging from cm-sized long-distance ballistic devices to nano-bead technology for veterinary species and wildlife.

Adjuvants, Immunologic↗
PubMed1996

Novel adjuvants and vaccine delivery systems.

Conventionally the efficiency of an adjuvant is measured by the capacity to induce enhanced antibody serum titres and cell mediated immunity (CMI) to a given antigen. Nowadays the capacity of an adjuvant is also measured by the quality as well as the magnitude of the induced immune response, guided by the protective immune response required. Quality includes isotype and IgG subclass responses, T-helper cell responses characterized by the cytokine profile and cytotoxic T cells (CTL). In the early phase of immunization some adjuvants influence the antigen administration and uptake by a so-called depot effect exemplified by aluminium hydroxide gel and oil adjuvants, which possibly is not as desired as alledged. A modern depot is exerted by slow release formulations continuously releasing the antigen over a period of time or by pulses at intervals aiming at 'single injection' vaccine. Great efforts are made to formulate efficient delivery formulations targeting the antigens from the site of administration, to draining lymph nodes or distant lymphatic tissue or to mucosal surfaces by parenteral or mucosal administrations. Nowadays, non-replicating carriers besides replicating vaccines are formulated to induce mucosal immune responses encompassing secretory IgA and CMI. Efforts to evoke immune responses on mucosal membranes distant from the site of administration have resulted mostly in little success. For a long time it was considered that CTL under the restriction of MHC Class I only could be evoked by replicating viruses or intracellular parasites. However, novel adjuvant delivery systems readily induce CTL by delivering the antigen to the APC resulting in intracellular transport to the cytosol for the MHC Class I presentation system, as well as to the endosomal pathway for the MHC Class II presentation.

Adjuvants, Immunologic↗