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Biomedical subjects

P D Minor

Publications and source records attributed to P D Minor.

At least 19 recordsLinked to original sources
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↗
PubMed1996

Testing plasma pools for markers of viral contamination: the UK experience.

The transmission of viral infections through the use of products derived from blood has emphasised the need for adequate validation of the production process, testing of materials used in production and quality control tests on the final product. Since the late 1980s, as part of its batch release procedures, NIBSC has tested for markers of viral infectivity plasma pools used in production of blood products used in the UK. As a result of testing over 9,000 pools, NIBSC has identified 9 pools contaminated with HBsAg and 2 pools containing antibodies to HIV-1. Since routine screening of plasma pools for anti-HCV was introduced in 1993, 8 pools out of the 4,000 tested have been found to contain antibodies to HCV. In addition, the release of 12 batches of blood products was withheld and it is known that further batches of material produced from the positive pools were not submitted for batch release. Studies involving assays of dilutions of known positive plasma samples indicated that there is considerable variation in the endpoint dilutions of antigen or antibody detected by test kits from different manufactures. The selection and validation of the kits used in such testing is therefore important. The usefulness of standardised low-level external controls in assays of plasma pools for markers of viral infection is discussed.

Antibodies, Viral↗
PubMed1996

Antigenic and genetic variation of the HN protein of mumps virus strains.

The relationships between different strains of mumps virus were established by determination of the sequence of the HN gene. They closely resemble those established from other portions of the genome, suggesting that the viruses are not recombinants over the areas examined. The relationships were consistent with those established by reaction with monoclonal antibodies raised against the Urabe strain, which has a similar antigenic structure to previously studied laboratory strains, and largely consistent with the specificity of the serological response of naturally infected or vaccinated human subjects.

Amino Acid Sequence↗
PubMed1996

Use of animals in the development and control of viral vaccines.

Animal models were central to the development of poliovaccines and remain essential in some form in the routine quality control of both live and killed vaccines. The necessity of an animal model is illustrated by the examples of mumps and measles vaccines where the existing materials, while satisfactory, have a number of drawbacks and where changes in current practice raise concerns for safety and efficacy.

Animal Testing Alternatives↗