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At least 127 records · Page 7Linked to original sources
PubMed1987

Vaccination of rabbits with a bovine herpesvirus type 1 subunit vaccine: adjuvant effect of ISCOMs.

Bovine herpesvirus type 1 has two major immunogenic surface glycoproteins: a 90 kDa haemagglutinin and the 130 (74 + 54) kDa glycoprotein. These proteins were purified by rate zonal sucrose density gradient centrifugation after extraction with nonionic detergent Triton X-100. For the preparation of ISCOMs, the glycoproteins were further adsorbed during a second rate zonal centrifugation, to micelles of Quil A glycoside, already added to the gradient. Haemagglutinating peaks were collected and used as subunit vaccine in rabbits: groups of three animals were injected with 50, 10 and 5 micrograms protein. Seroconversion was followed by ELISA, haemagglutination inhibition, neutralizing and plaque reduction assays. ISCOMs and unadsorbed subunits were efficient in inducing neutralizing as well as haemagglutination inhibiting antibodies: ISCOMs gave a higher level of response. The efficiency demonstrated by ISCOMs suggests their potential as a subunit vaccine.

Adjuvants, Immunologic↗
PubMed1988

Control of infectious bovine rhinotracheitis in calves with a BHV-1 subunit-ISCOM vaccine.

An ISCOM subunit vaccine was prepared by adsorption of purified viral membrane proteins of BHV-1 on the glycoside Quil A and assayed in six-month-old seronegative calves. Groups of five animals were given three intramuscular doses of 50 or 25 micrograms BHV-1/ISCOMs or a commercial attenuated vaccine. Both types of vaccine induced seroconversion: the ISCOM vaccine consistently gave a serological response superior to that of the attenuated vaccine with maximal titres of 1/608 in haemagglutination inhibition and 1/53 in neutralization for the 50 micrograms dose compared to 1/152 haemagglutination units and 1/16 neutralizing titres for the attenuated vaccine. Calves vaccinated with the ISCOM vaccine were protected upon challenge whereas control animals showed signs of respiratory distress, and calves vaccinated with the attenuated vaccine developed only mild respiratory tract infection and mild increased rectal temperature. Virus shedding was reduced 100-fold in the attenuated vaccine group compared to 10,000-fold reduction in the ISCOM vaccine groups. The high level of protection induced indicates the potential of BHV-1/ISCOM as a subunit vaccine.

Animals↗
PubMed1988

Local reactions of the saponin Quil A and a Quil A containing iscom measles vaccine after intramuscular injection of rats: a comparison with the effect of DPT-polio vaccine.

A short-term toxicity study was performed to investigate local reactions and hematological changes after im injection of Quillaia A (Quil A; 50 or 600 micrograms/ml) an essential component of an immunostimulating complex (iscom), a novel form of a subunit vaccine, and of iscom measles vaccine containing 360 micrograms Quil A/ml. The effects were compared with those caused by a sterile phosphate-buffered saline solution and by diphtheria-pertussis-tetanus-polio (DPT-polio) vaccine. Groups of six male rats were injected im with 0.25 ml of the test solution: on Day 0 in the left and on Day 7 in the right musculus gastrocnemius. On Day 14 the animals were killed, and the left and right inguinal lymph nodes were weighed. These organs and the left and right musculus gastrocnemius were investigated microscopically. The only hematological changes observed occurred in the group injected with DPT-polio vaccine: a decrease in the Hb value and in the number of erythrocytes and an increase in mean corpuscular hemoglobin content and in the number of leucocytes. The weights of the left and right inguinal lymph nodes were significantly increased in rats injected with DPT-polio vaccine, iscom measles vaccine, and the high dose of Quil A. The most intense granulomatous inflammatory reaction, mainly consisting of activated macrophages, was observed at the injection sites of all animals of the DPT-polio group. Only one animal injected with the iscom measles vaccine showed a moderate inflammatory reaction of the same type.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Quaternary structure of the immunostimulating complex (iscom).

Proteins of either HIV-1, hepatitis B, or rabies virus were incorporated with the adjuvant substance Quil A and cholesterol into the immunostimulating complex: iscom. Formation and symmetry of this regular complex were analyzed by electron microscopy. Micellar structures with a diameter of about 12 nm, occasionally with a 7-nm stain-filled center, were formed in a 0.03% water suspension of Quil A. Cavities or holes appeared in the smooth structures of cholesterol upon the addition of Quil A, and after mixing Quil A and cholesterol 1:1 fragile and flattened structures of matrix were produced with a diameter of about 40 nm. By freeze-drying the matrix was preserved as a cage-like, isometric particle. Stable iscom particles composed of Quil A, cholesterol, and selected viral proteins had an approximate diameter of 32 nm. The particles had an uniform, cage-like structure, exhibiting icosahedral symmetry, irrespective of the viral proteins incorporated. Tilting experiments and rotational image analysis indicated that the iscoms were composed of 20 morphological subunits assembled in a pentagonal dodecahedron with a hole on each of the 12 pentagonal faces. The symmetrical shape of the iscom might explain both its remarkable stability and its capacity to efficiently present antigens to the immune system.

Adjuvants, Immunologic↗
PubMed1988

Cellular immune responses in the murine lung to local immunization with influenza A virus glycoproteins in micelles and immunostimulatory complexes (iscoms).

Primary immunization with a single inoculum of either micelles or iscoms containing influenza A virus glycoproteins failed to induce either B or cytotoxic T (Tc) cell responses. In contrast, immunization with two inocula of iscoms, but not micelles, resulted in the appearance of influenza virus-specific antibody-secreting cells (ASC) but not Tc cells in the lung. There was a 10-fold increase in Tc cell precursor frequency and an increase in ASC generated by secondary in vitro stimulation of lung cell cultures obtained from mice primed with iscoms but not micelles. In mice primed with infectious virus, secondary immunization with either micelles or iscoms increased the number of ASC in the lung and elicited virus-specific Tc cell responses. In contrast homologous virus challenge failed to induce detectable secondary B or Tc cell responses.

Animals↗
PubMed1990

Iscom (immunostimulating complex) vaccines containing mono- or polyvalent pili of enterotoxigenic E. coli; immune response of rabbit and swine.

Iscom (immunostimulating complex) vaccines were prepared to contain K88ab, K88ac, K99 and 987P pili (fimbriae) of enterotoxigenic E. coli bacteria as monovalent or quadrivalent preparations. The iscoms injected into rabbits and into pigs elicited similar or higher immune response in both animal species than the oil adjuvanted vaccine containing about 5 times more of the same pilus protein. It is concluded that inclusion of pili into iscoms results in immunogenic preparations likely worth pursuing for vaccine production against enterotoxic colibacillosis of newborn pigs. The iscoms did not induce local reaction at the injection sites in contrast to the oil adjuvanted vaccines.

Adjuvants, Immunologic↗
PubMed2003

Generating neutralizing antibodies, Th1 response and MHC non restricted immunogenicity of HIV-I env and gag peptides in liposomes and ISCOMs with in-built adjuvanticity.

For enhancing immunogenicity and develop vaccine strategies using peptide based constructs against HIV-1, a chimeric peptide containing V3 loop and transmembrane sequence of gp41 with two glycine motifs as spacer was constructed. The V3-gp41, gp41 peptide and p17 and p24 peptides separately or in a cocktail were entrapped with or without MA729 as an immunoadjuvant in liposomes or ISCOMs. The immunogenicity, antigen induced T-cell proliferation and cytokine profiles of various formulations were studied in four different inbred strains of mice of H-2d, H-2b, H-2k and H-2q haplotypes, keeping alum as a control adjuvant. Both liposomes and ISCOM preparations elicited high titer and long lasting antibody response (60 days and above). When compared to the alum formulation, the liposomes co-entrapped with MA729 produced high antibody levels, comparable with that induced by ISCOMs. Peptide in alum, liposomes and ISCOMs enhanced both antigen specific IgG2a and IgG2b isotypes and high T-cell stimulation index. Peptide formulations also induced antibodies with high affinity and in vitro neutralizated the formation of HIV-1 syncytia. T-cell supernatants contained high levels of IFN-gamma and IL-2. Thus formulation in these adjuvants induced a predominant Th1 like response with MA729 as a versatile novel delivery vehicle for stimulating the appropriate arm of the immune response that can selectively modulate MHC class I or MHC class II response. The above peptide can be of wide vaccination interest as a means to improve immune responses to several other HIV-1 antigens and may serve as candidates for vaccine development.

Journal Article↗
PubMed1993

Plasmodium falciparum: the immune response in rabbits to the clustered asparagine-rich protein (CARP) after immunization in Freund's adjuvant or immunostimulating complexes (ISCOMs).

The Plasmodium falciparum clustered asparagine-rich protein (CARP) is a merozoite-associated antigen which contains approximately 30% asparagine. Analysis of the DNA sequences located 5' of the cloned 1.4-kb CARP gene in the P. falciparum genome suggests that this gene fragment may encode the complete CARP and that the gene product is a protein of M(r) 50,000. To analyze the immunogenicity of CARP, the gene was expressed as a fusion protein with staphylococcal protein A (SpA-CARP). Immunization of rabbits with SpA-CARP in Freund's complete adjuvant (FCA) resulted in a strong antibody response against CARP as measured in ELISA. This response was efficiently boosted and sustained over a long time while that induced by two immunizations with SpA-CARP in ISCOMs was weak and of shorter duration. In both instances, the antibody levels against CARP were further increased by a second booster injection consisting of either SpA-CARP or CARP fused to the serum albumin-binding region (BB) of streptococcal protein G (BB-CARP) in PBS, indicating that immunizations with SpA-CARP in FCA or ISCOMs had induced a CARP-specific immunological memory. Boosting with BB-CARP in PBS was more efficient than boosting with SpA-CARP in PBS. In all rabbits, the antibodies obtained after the booster with CARP in PBS were the most efficient inhibitors of merozoite invasion in vitro. The antisera reacted with the intracellular parasite in immunofluorescence and with a band of M(r) 50,000 in immunoblotting while several high-molecular-weight components as well as the one of M(r) 50,000 were immunoprecipitated. The specificity of the antibody responses varied between the different rabbits as indicated in ELISA, with short synthetic peptides representing different CARP sequences. Taken together, the results suggest that a previously cloned genomic DNA fragment may encode the complete P. falciparum blood-stage antigen CARP and that CARP is immunogenic in rabbits both when administered in FCA or ISCOMs.

Amino Acid Sequence↗
PubMed1994

Conjugation of synthetic peptides to carrier iscoms: factors affecting the immunogenicity of the conjugate.

This study was designed to explore optimal conditions for the conjugation of a synthetic peptide to preformed influenza virus iscoms using MHS (maleimidohexanoyl-N-hydroxy-succinimide ester) as coupling agent. The peptide used in this study comprised amino acids 122-138 of porcine growth hormone (pGH). Different ratios of peptide to carrier iscoms were tested and the resulting conjugates were analysed for composition, antigenicity and immunogenicity. The problem of low solubility and poor immunogenicity of high-density peptide conjugates is discussed and a general protocol for conjugation of peptides to carrier iscoms is proposed.

Animals↗
PubMed1991

Protective effect of an ISCOM bovine virus diarrhoea virus (BVDV) vaccine against an experimental BVDV infection in vaccinated and non-vaccinated pregnant ewes.

Fifteen pregnant ewes were vaccinated twice with an experimental immunostimulating complex (ISCOM) subunit vaccine designed to contain the envelope proteins of a Danish cytopathic bovine virus diarrhoea virus (BVDV). The serological responses were measured in ELISA and virus neutralization (VN) tests. All ISCOM-vaccinated ewes developed high VN antibody titres to BVDV in contrast to the 14 non-vaccinated ewes. Both groups of ewes were challenged parenterally when 48-65 days pregnant with a Swedish cytopathic BVDV isolate. In the vaccinated group 26 fetuses out of 29 detected by ultrasound were liveborn, whereas only six out of 26 were liveborn in the non-vaccinated group. It is concluded that the ISCOM vaccine had the potential of eliciting high VN titres as well as protecting fetuses against transplacental infection after challenge with a virulent BVDV isolate.

Animals↗
PubMed1994

Immune responses and protective effect in mice vaccinated orally with surface sporozoite protein of Eimeria falciformis in ISCOMs.

Immunostimulating complexes (ISCOMs) were built after treatment of a purified surface protein from Eimeria falciformis sporozoites with a palmitic acid derivation, leading to a high ratio (33-64%) of P27 incorporation in these cage-like structures. P27 kept its antigenicity after incorporation in ISCOMs, which induced, after iterative intubations by the oral route to groups of mice, a systemic IgG response, a local IgA response, and a local enhanced cellular response as demonstrated by lymphoproliferation of mesenteric lymph node cells upon in vitro stimulation with antigen. This immunization (120 micrograms in six oral doses at 2-day intervals) afforded mice a partial protection (60%) against a subsequent 400 oocyst challenge. The reduction in daily oocyst excretion was corroborated by significantly different weight losses between immunized and control mice on days 9 and 10 postinfection and the subsequent death of these control mice. These observations provide the first application of ISCOMs to parasitic intestinal diseases.

Administration, Oral↗
PubMed1994

Antigenicity and immunogenicity of experimental equine influenza ISCOM vaccines.

A comparison of the antigenicity and immunogenicity of ISCOM vaccines prepared from equine influenza viruses H3N8 and H7N7 was made with inactivated whole-virus vaccines containing equivalent amounts of virus haemagglutinin. ISCOMs stimulated superior antibody responses in terms of both amount and duration. As with conventional whole-virus vaccines, the levels of antibody to virus haemagglutinin induced by ISCOMs correlated with protection.

Animals↗
PubMed1996

Linkage of a fusion peptide to a CTL epitope from the nucleoprotein of measles virus enables incorporation into ISCOMs and induction of CTL responses following intranasal immunization.

The introduction of soluble protein antigens into the endogenous processing pathway is a prerequisite for the efficient induction of MHC class-1 restricted cytotoxic T-lymphocytes (CTLs). Antigens incorporated into immunostimulating complexes (ISCOMs) containing lipids and Quil-A are able to induce CD8+ CTL responses in vivo. Furthermore, lipopeptides have also been used to raise peptide-specific CTLs and bypass the requirement for the use of an adjuvant. Although conventional ISCOM technology is in general restricted to the use of hydrophobic proteins or fatty acid-derivitized proteins or peptides, we have demonstrated that the linkage of a conserved paramyxovirus fusion peptide to a CTL epitope NP29 (residues 281-290 of measles virus nucleoprotein) resulted in the incorporation of this hydrophilic CTL epitope into ISCOMs and the in vivo priming of peptide specific CTLs following intranasal immunization. In addition, the fusion peptide-CTL epitope chimera was able to efficiently sensitise P815 target cells for lysis by nucleoprotein specific CTLs induced following immunization of mice with recombinant RAd-68 adenovirus, suggesting the efficient introduction of the peptide into the class-1 restricted antigen processing pathway. Furthermore, immunization of mice with this fusion peptide chimera in saline was able to prime an NP29-specific CTL response despite the absence of adjuvant.

3T3 Cells↗
PubMed2005

Quil A-lipid powder formulations releasing ISCOMs and related colloidal structures upon hydration.

The aim of the present study was to prepare solid Quil A-cholesterol-phospholipid formulations (as powder mixtures or compressed to pellets) by physical mixing or by freeze-drying of aqueous dispersions of these components in ratios that allow spontaneous formation of ISCOMs and other colloidal structures upon hydration. The effect of addition of excess cholesterol to the lipid mixtures on the release of a model antigen (PE-FITC-OVA) from the pellets was also investigated. Physical properties were evaluated by X-ray powder diffractometry (XPRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and polarized light microscopy (PLM). Characterization of aqueous colloidal dispersions was performed by negative staining transmission electron microscopy (TEM). Physically mixed powders (with or without PE-FITC-OVA) and pellets prepared from the same powders did not spontaneously form ISCOM matrices and related colloidal structures such as worm-like micelles, ring-like micelles, lipidic/layered structures and lamellae (hexagonal array of ring-like micelles) upon hydration as expected from the pseudo-ternary diagram for aqueous mixtures of Quil A, cholesterol and phospholipid. In contrast, spontaneous formation of the expected colloids was demonstrated for the freeze-dried lipid mixtures. Pellets prepared by compression of freeze-dried powders released PE-FITC-OVA slower than those prepared from physically mixed powders. TEM investigations revealed that the antigen was released in the form of colloidal particles (ISCOMs) from pellets prepared by compression of freeze-dried powders. The addition of excess cholesterol slowed down the release of antigen. The findings obtained in this study are important for the formulation of solid Quil A-containing lipid articles as controlled particulate adjuvant containing antigen delivery systems.

Adjuvants, Pharmaceutic↗
PubMed2004

Immune responses and protective efficacy in ponies immunised with an equine influenza ISCOM vaccine containing an 'American lineage' H3N8 virus.

Protective responses generated by vaccination with an immuno-stimulating complex (ISCOM)-based vaccine for equine influenza (EQUIP F), containing a new 'American lineage' H3N8 virus, were studied. Seven ponies in the vaccine group received two intramuscular injections of EQUIP F given 6 weeks apart. Aerosol challenge with an A/eq/Newmarket/1/93 reference strain 4 weeks after booster vaccination resulted in clinical signs of infection and viral shedding in 7 influenza-naive control animals whereas the vaccinated ponies were significantly protected from both clinical signs and virus excretion. Influenza virus-specific IgG responses in serum following immunisation with the ISCOM vaccine were predominantly of the IgGa and IgGb sub-isotypes, a pattern similar to that generated by equine influenza virus infection. However, in contrast to the response following infection, virus-specific antibody responses in nasal washes following immunisation were characterised by the presence of IgG but not IgA.These results demonstrated that an ISCOM-based vaccine containing A/eq/Kentucky/98 provides strong protective immunity against challenge with an 'American lineage' H3N8 reference virus.

Animals↗
PubMed2000

A randomized, double blind study in young healthy adults comparing cell mediated and humoral immune responses induced by influenza ISCOM vaccines and conventional vaccines.

Although current influenza vaccines have been shown to reduce influenza-related morbidity and mortality, there is a desire to develop more efficacious products. Vaccines which can induce CD8(+) cytotoxic T cell (CTL) responses in addition to strong antibody responses may be more effective in preventing disease since it has been demonstrated that CTL contribute to protective immunity, even against drift variants of influenza A viruses. The immunogenicity of two types of experimental influenza vaccines, which were based on immune stimulating complexes (ISCOM), were evaluated and compared with a conventional non-adjuvanted inactivated split virion vaccine, after immunization of human volunteers. In this randomized, double blind study, it was shown that the ISCOM vaccines altered the kinetics of the serum antibody response, resulting in more rapid titer rises against the vaccine strains. This accelerated antibody response coincided with enhanced in vitro proliferative T cell responses, which were observed shortly after vaccination. In addition, CTL responses were observed in a higher proportion of the vaccinees receiving an ISCOM vaccine, than in vaccinees receiving the conventional influenza vaccine.

Adjuvants, Immunologic↗
PubMed2001

Rinderpest virus (RPV) ISCOM vaccine induces protection in cattle against virulent RPV challenge.

Rinderpest virus (RPV), a member of genus Morbillivirus in the family Paramyxoviridae, causes an acute and often fatal disease in cattle and other large ruminants. A subunit rinderpest vaccine consisting of an immune-stimulating complex (ISCOM) incorporating the RPV haemaggulutinin (H) protein, was examined for its ability to induce protective immunity in cattle, the natural host of RPV. All of four cattle vaccinated with the ISCOM vaccine survived challenge with virulent virus. Three were solidly protected, showing no clinical signs of infection, while the fourth animal developed only mild and transient symptoms. Virus neutralizing antibodies were produced at a significant level in all vaccinated cattle. These results indicate that this ISCOM vaccine is effective in producing protective immunity in cattle and should be a suitable means of delivering glycoprotein antigens from other morbilliviruses.

Animals↗
PubMed2001

Intranasal immunisation with influenza-ISCOM induces strong mucosal as well as systemic antibody and cytotoxic T-lymphocyte responses.

Intranasal administration of vaccines is preferred for induction of mucosal immune responses. In this study, mice were immunised intranasally and subcutaneously with influenza-immuno stimulating complexes (influenza-ISCOM). The intranasal dose was 15-times the subcutaneous dose. All mice dosed with influenza-ISCOMs survived challenge with live virus and comparable serum antibody and splenic cytotoxic T-lymphocyte responses were detected in both groups. Induction of mucosal IgA was significantly higher with intranasal immunisation and was comparable to responses induced with the heat labile enterotoxin of Escherichia coli as adjuvant. These findings demonstrate that intranasal administration of high dose influenza-ISCOM results in potent systemic and mucosal immune responses.

Adjuvants, Immunologic↗