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Biomedical subjects

P D Minor

Publications and source records attributed to P D Minor.

At least 55 records · Page 3Linked to original sources
PubMed1999

Potential of polymeric lamellar substrate particles (PLSP) as adjuvants for vaccines.

In recent years microspheres or microparticles produced from biodegradable polymers such as poly(D,L-lactide) (PLA) and poly(D, L-lactide-co-glycolide) (PLGA) containing encapsulated vaccine antigens have been investigated for administration via parenteral, oral, and intranasal routes. These microparticles allow the controlled release of vaccines with an aim to reduce the number of doses for primary immunisation or to develop single dose vaccines. The polymer materials have been widely regarded as being of minimal toxicity. Evaluation of candidate systems in animal studies have shown antibody levels and cell responses similar to or greater than those observed with adjuvants such as alum. However, there are concerns regarding the integrity and immunogenicity of the antigen during the encapsulation process when the antigen is exposed to organic solvents, high shear stresses and the exposure of antigen to low pH which is caused by polymer degradation. An alternative approach would be to adsorb antigens to the surface of biodegradable polymer particles. Polymeric lamellar substrate particles (PLSP), produced by a simple precipitation of PLA, are suitable for this purpose. The adsorption of antigens onto these particles is a simple procedure. It avoids pH changes due to bulk polymer degradation and the use of solvents and therefore will be less damaging to the vaccine. Moreover, such systems will be much easier to scale up for a clinical study and eventual manufacture. The aim of this article is to discuss the preparation and physical characteristics of PLSP, antigen adsorption, in vivo efficacy of PLSP antigen systems and to consider the potential of PLSP as controlled release adjuvants for protein, peptide or viral vaccines.

Adjuvants, Immunologic↗
PubMed1999

The influence of the host cell on standardisation of influenza vaccine potency.

Conventional influenza vaccines are standardised using the single-radial-immunodiffusion (SRD) test where reagents are produced from egg-grown viruses. It is important to ensure homology between SRD antigen reagents and test vaccines. There was concern that cell-grown vaccines may differ antigenically from corresponding egg-grown vaccines, which may in turn affect vaccine standardisation. In an examination of five cell-grown vaccines from two companies, only one vaccine was affected by the specificity of the SRD test. Options for standardisation of cell-grown vaccines are considered and recommendations are made for further studies.

Animals↗
PubMed1998

Studies on the loss of infectivity of live type 3 poliovaccine on storage.

The Children's Vaccine Initiative established a Product Development Group in 1991 to help in the development of oral poliovaccines of improved thermostability. Under the auspices of this group, the effect of different stabilizers on the loss of infectivity of commercial monovalent type 3 live poliovaccine bulks at 37 degrees C, 42 degrees C and 45 degrees C has been examined. The only effective conditions were the maintenance of the pH at 6.5, and the use of deuterium oxide at a concentration of 90%. All other additives, including detergents, albumin, antiviral compounds, sucrose and magnesium chloride, alone or in combination either had no effect or increased the rate of loss of infectivity.

Antiviral Agents↗
PubMed1998

Resorbable lamellar particles of polylactide as adjuvants for influenza virus vaccines.

Lamellar particles and microspheres were produced by precipitation from solutions of resorbable, biocompatible, semi-crystalline poly(L-lactide)[PLA] and amorphous poly(DL lactide co-glycolide)[PLG] copolymer, respectively, to investigate their adjuvanticity towards adsorbed influenza virus. Both types of substrate were capable of adsorbing large quantities of virus (> 15% w/w) and retaining virus (> 60% of the initial load) over an 8 week time scale in-vitro. Potent immune responses were obtained in mice after the intra-muscular injection of adsorbed vaccine systems. The response to virus adsorbed on PLA lamellar particles was almost five times that obtained using PLG microspheres and fourteen times that using aqueous vaccine. The lamellar forms of PLA may function as an immunomodulator enhancing phagocytic activity due to their irregular shape and may be useful in improving the immune response to a variety of protein and viral antigens.

Adjuvants, Immunologic↗
PubMed1998

Role for beta2-microglobulin in echovirus infection of rhabdomyosarcoma cells.

A monoclonal antibody (MAb) that blocks most echoviruses (EVs) from infecting rhabdomyosarcoma (RD) cells has been isolated. By using the CELICS cloning method (T. Ward, P. A. Pipkin, N. A. Clarkson, D. M. Stone, P. D. Minor, and J. W. Almond, EMBO J. 13:5070-5074, 1994), the ligand for this antibody has been identified as beta2-microglobulin (beta2m), the 12-kDa protein that associates with class I heavy chains to form class I HLA complexes. A commercial MAb (MAb 1350) against beta2m was also found to block EV7 infection without affecting binding to its receptor, DAF, or replication of EV7 viral RNA inside cells. Entry of EV7 into cells was reduced by only 30% by antibody and cytochalasin D, an inhibitor of endocytosis mediated by caveolae and clathrin-coated pits, but was not significantly reduced by sodium azide. The block to virus entry by cytochalasin D was additive to the block induced by antibody. We suggest that EV7 rapidly enters into a multicomponent receptor complex prior to entry into cells and that this initial entry event requires beta2m or class I HLA for infection to proceed.

Animals↗
PubMed1998

Absence of detectable measles virus genome sequence in inflammatory bowel disease tissues and peripheral blood lymphocytes.

A highly sensitive measles-specific RT-PCR-nested PCR system was established, which consistently amplified measles virus genome sequence from control samples containing as little as 5.5 x 10(-3) pfu per reaction. This method failed to detect the presence of measles virus in 93 colonoscopic biopsies and 31 peripheral blood lymphocyte preparations, examined and obtained from patients with inflammatory bowel disease (IBD) and noninflammatory controls. All patients had detectable levels of serum neutralization antibody against measles virus. Each biopsy was estimated to have about one million cells, based on the amplification of the beta actin gene. The assay was calibrated by use of a known number of lymphocytes. The method applied was able to amplify measles virus RNA from a nucleic acid mixture equivalent to 18 cells derived from subacute sclerosing panencephalitis (SSPE) brain material. The level of measles RNA present, if any, in the biopsies is therefore at least 50,000-fold less than in SSPE.

Adult↗
PubMed1998

Examination of poliovaccines for the presence of SV40 sequences.

Batches of monovalent oral poliovirus vaccine bulks previously screened for infectious SV40 by cell culture methods and used in the United Kingdom from 1971-96 in trivalent oral poliovirus vaccine have now been examined by a newly developed PCR for the presence of SV40 sequences. Up to April 1997, over 190 batches have been examined. SV40 sequences were not detected in any of the vaccines. This provides additional assurance that oral poliovirus vaccines used in the U.K. from 1971 are free of SV40 contamination.

Animals↗
PubMed1997

RT-PCR based diagnosis and molecular characterisation of mumps viruses derived from clinical specimens collected during the 1996 mumps outbreak in Portugal.

Clinical specimens collected during an outbreak of mumps were characterised by RT-PCR, nested PCR, and nucleotide sequencing. Mumps virus was positively identified in 12/21(57%) saliva, 9/21(43%), throat and 1/33(3%) urine specimens and further sequence comparison revealed that at least six strains of viruses, which differed from 0-9.43% at the nucleotide levels, were cocirculating during the epidemic. However, phylogenetic analysis showed that these viruses grouped with two previously identified lineages which were mostly composed of other European mumps virus isolates.

Adolescent↗
PubMed1997

Laboratory tests for mumps vaccines.

The action of live attenuated vaccines against mumps is poorly understood although their clinical efficacy is beyond doubt. The attenuated character of the vaccine is assured by consistency of production related to clinical trials, and limited studies of vaccine seeds in primates. Potency is assessed by infectivity in vitro and is subject to poorly understood sources of variation. Molecular biological studies are at an early stage.

Animals↗
PubMed1997

Clustering of mumps virus isolates by SH gene sequence only partially reflects geographical origin.

The nucleotide sequences of the SH gene of 45 new mumps virus isolates derived from different parts of Europe, Canada and USA were determined. A phylogenetic tree was constructed which confirmed the existence of three major clusters. While clustering according to geographical origin was clear in some cases each of the major clusters included isolates which were widely separated in origin. The degree of variability between the sequences of SH genes of different strains and the ratio of coding to non coding differences were both very high compared to those observed in other genes such as the M and HN. A standardized system of nomenclature of mumps strains was established.

Amino Acid Sequence↗
PubMed1997

Genetic variation among strains of wild-type yellow fever virus from Senegal.

We have examined and compared at the molecular level three strains of wild-type yellow fever (YF) virus isolated from Senegal in 1927, 1953 and 1965, termed French viscerotropic virus, Rendu and Dak1279 respectively. Over the structural protein genes, Rendu differed from the other two strains by 8% at the nucleotide level. Rendu also differed antigenically, possessing a 'vaccine'-specific envelope (E) protein epitope (i.e. an epitope previously shown to be found on 17D and French neurotropic vaccine viruses only and not wild-type strains of YF virus). Consequently, we propose that at least two distinct genotypes of wild-type YF virus have been present in Senegal. Since Rendu virus was isolated from a fatal case of YF, it would indicate that the vaccine-specific epitope on the E protein is not associated with attenuation of the viscerotropism of wild-type YF virus.

Genotype↗
PubMed1996

Poliovirus biology.

Poliomyelitis has been largely controlled by the use of attenuated live vaccine strains. The molecular basis of attenuation is beginning to be understood, but the interactions between the virus and its human host remain mysterious.

Humans↗
PubMed1996

A novel cytopathic microtitre plate assay for hepatitis A virus and anti-hepatitis A neutralizing antibodies.

The slow growth of hepatitis A virus (HAV) has made tissue culture assay for infectious virus difficult. Strains of the virus of greater cytopathogenicity have been selected for use in plaque cytopathic assays. However, in our hands, this assay has been difficult to reproduce consistently due to problems in maintaining intact cell monolayers over the long incubations involved. This report describes the development of a cytopathic TCID50 assay for HAV. From the results of repeated assay of one preparation of the virus, the coefficient of variation of the assay was calculated to be 4%. This assay has also been adapted to quantitate antibodies to HAV. Initial results of assaying the WHO standard immune serum globulin are comparable with the titre obtained by the radioimmunofocus inhibition test. Antibody titres in human and mouse sera could also be quantitated. The cytopathic TCID50 assay and the adapted inhibition assay described, may prove useful for the development and control of HAV vaccines and the validation of viral inactivation protocols.

Animals↗