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F Brown

Publications and source records attributed to F Brown.

At least 91 records · Page 5Linked to original sources
PubMed1995

Vaccination today and tomorrow.

The vaccines against infectious diseases in use today are, with few exceptions, prepared from the causal agents themselves, either by inactivating them with a chemical such as formaldehyde or by attenuating them so that they grow and thus evoke an immune response in the natural host but cause no disease. These empirical approaches have produced many highly successful vaccines. Increasing knowledge at the molecular level of the agents and of the immune response to protein antigent is now providing us with the opportunity to design vaccines that will elicit protective responses without the need to use the agents themselves. The critical issue is to identify the immune responses that correlate with protection.

Animals↗
PubMed1995

Identification of native foot-and-mouth disease virus non-structural protein 2C as a serological indicator to differentiate infected from vaccinated livestock.

Cattle and pigs which have been vaccinated against foot-and-mouth disease can be distinguished from convalescent animals by radio-immunoprecipitation and sodium dodecyl sulphate polyacrylamide gel electrophoresis of the virus-induced proteins reacting with the respective sera. Baby hamster kidney cells infected with foot-and-mouth disease virus (FMDV) (serotype A24) were labelled with 35S-methionine and the virus-induced proteins were precipitated with sera from vaccinated and subsequently challenged animals, convalescent animals retained for over 300 days, animals vaccinated or infected with viruses belonging to all serotypes of FMDV, and animals infected with encephalomyocarditis (EMC) or porcine or bovine enteroviruses. In addition to the structural proteins of the virus, the non-structural proteins 2C, 3ABC, 3C, 3CD and 3D were precipitated by convalescent sera, but only 3D was precipitated by serum from vaccinated animals. Proteins L, 2C and 3C were precipitated only after challenge with a heterotypic virus (serotype O1 Tunisia), indicating that virus replication of the challenge virus had taken place. No precipitation was detected with sera from EMC or enterovirus-infected animals. The results indicate that protein 2C, and to a lesser extent the polypeptide 3ABC, could be used to differentiate potential carrier convalescent animals from vaccinated livestock.

Animals↗
PubMed1995

Antigenic variants in a plaque-isolate of foot-and-mouth disease virus: implications for vaccine production.

The occurrence of many subtypes within a serotype of foot-and-mouth disease virus (FMDV) makes it difficult to control the disease by vaccination. Although inactivated vaccines are used successfully in many countries, the appearance in the field of antigenic variants against which the vaccines do not confer protection is a constant problem in vaccine manufacture. We had found previously a mixture of antigenic variants in a field isolate of serotype A12. In this report we demonstrate the presence of two variants in a plaque-isolate from this mixture. The second variant was detected only when the growth conditions were altered. Our observation points to the problems which may be encountered in the large scale growth of a virus for vaccine production.

Amino Acid Sequence↗
PubMed1995

Stabilising oral poliovaccine at high ambient temperatures.

The oral poliovaccine strains lose infectivity when they are stored above refrigerator temperatures. These losses increase rapidly at the high temperatures encountered in tropical countries, thus causing problems if the cold chain is inadequate. Attempts to minimise these losses have generally relied on the addition of salts such as MgCl2. In this paper we show that the fall in infectivity, which is due to the hydrolysis of the genomic RNA by the RNA polymerase within the virus particle, can be greatly inhibited by the suppression of this enzymatic activity. This can be achieved simply by reducing the pH below 7.

DNA-Directed RNA Polymerases↗
PubMed1995

Structure and immunogenicity of experimental foot-and-mouth disease and poliomyelitis vaccines.

The physico-chemical properties and immunogenicity of experimental vaccines against foot-and-mouth disease (FMD) and poliomyelitis, prepared by treatment of the viruses with N-acetylethyleneimine (AEI), formaldehyde or neutral red, have been studied. None of these reagents affects the rate of sedimentation of the particles or their reaction with antibody against the major immunogenic sites. FMD vaccines prepared by inactivation with AEI or neutral red, behaved like the untreated virus, in that they were disrupted on lowering the pH below 7. The RNA of the AEI-inactivated virus was degraded into slowly sedimenting molecules. Unlike AEI-inactivated virus, from which all the RNA could be extracted with phenol-SDS, the recovery from the neutral red inactivated virus was variable and was sometimes as low as 40%; this RNA gave a heterogenous profile in sucrose gradients. The capsid proteins in the AEI preparation migrated in SDS-PAGE to the same positions as those of untreated virus, but in the neutral red preparation there was evidence of cross-linking. In contrast, the formaldehyde-inactivated vaccine was stable below pH 7 and the RNA could not be released by extraction with phenol-SDS at pH 5, because the capsid proteins had become cross-linked and/or linked to the RNA. As with foot-and-mouth disease virus (FMDV), poliovirus which had been inactivated with formaldehyde did not release its RNA on extraction with phenol-SDS and the capsid proteins were also cross-linked. Surprisingly, although AEI cleaved the viral RNA slowly in situ, the virus was no longer infectious after 6 h. Neutral red did not reduce the infectivity of the virus. All of the preparations gave similar levels of neutralizing antibody after a single inoculation. The high levels obtained with the formaldehyde-inactivated vaccines have implications for the processing of fixed particles by the antigen-presenting cells.

Animals↗
PubMed1995

Differences in qualitative brain morphology findings in schizophrenia, major depression, bipolar disorder, and normal volunteers.

This study examined the frequency and type of qualitative brain morphologic anomaly as a function of sex and diagnosis. Magnetic resonance imaging brain scans were evaluated by an experienced neuroradiologist blind to diagnosis. The scans of 325 individuals (108 schizophrenic, 20 schizoaffective, 27 major depressive, 20 bipolar and 150 healthy volunteers) were categorized into one of five groups: normal, hyperintensity signals, volume loss, ventricular anomaly or "other" abnormality. Schizophrenic men had significantly more morphologic anomalies, especially of the lateral ventricles than healthy male volunteers. Schizophrenic women did not differ from healthy women. Schizoaffective patients of both sexes, male depressive and female bipolar patients were also characterized by higher rates of brain anomalies. Independent of diagnosis, women were more likely than men to have hyperintensity signals among individuals with positive scan findings. The overall rate of brain morphologic anomalies is significantly higher among male schizophrenic patients than healthy volunteers; this is not specific to male schizophrenics, however, suggesting a global sex effect. Type of anomaly may differ by sex and give us clues about sex differences in the pathophysiology of psychopathology.

Adult↗
PubMed1994

Circular dichroism, molecular modeling, and serology indicate that the structural basis of antigenic variation in foot-and-mouth disease virus is alpha-helix formation.

Seven antigenic variants obtained from a single field isolate of foot-and-mouth disease virus, serotype A12, differ only at residues 148 and 153 in the immunodominant loop of viral protein VP1. Synthetic peptides corresponding to the region 141-160 are highly immunogenic. UV circular dichroism shows that (i) in aqueous solution the peptides are nearly identical, but in 100% trifluoroethanol they display helix-forming properties which correlate well with their serological crossreactivities for anti-peptide sera, and (ii) these properties are insensitive to substitutions at position 153, except for proline, but are highly sensitive to substitutions at position 148. This pattern can be explained by the effects of these substitutions on the amphiphilic character and positions of helices postulated in the region 146-156. Molecular models indicate that residues 147, 148, 150, 151, 153-155, and 157 are most likely to interact with residues of the antibody paratopes. The data are consistent with the existence of an inverse gamma-turn around Pro-153, and a beta-turn at the cell-attachment site at residues 145-147.

Amino Acid Sequence↗
PubMed1994

The Leeuwenhoek Lecture, 1993. Peptide vaccines: dream or reality?

Small fragments of micro-organisms which elicit protective immune responses have now been identified for several disease-causing agents. This major advance has made it possible to envisage the chemical synthesis of vaccines which could replace those in current use and may also furnish products which cannot be made by traditional methods. In my lecture I will illustrate the principles involved by describing the advances made with synthetic vaccines for foot-and-mouth disease, hepatitis B and malaria.

Animals↗
PubMed1994

Foot-and-mouth disease virus particles contain replicase protein 3D.

An antibody against the Escherichia coli-expressed RNA polymerase of foot-and-mouth disease virus (FMDV) reacts with the virus in ELISA and radioimmunoprecipitation experiments and with a protein of the disrupted virus particle in an immunoblot analysis. Treatment of the virus with trypsin, which cleaves capsid protein VP1 and a 56-kDa polypeptide present in trace amount in the particles, reduces the level of the reaction in ELISA and radioimmunoprecipitation and eliminates the immunoblot reaction. Electron microscopy showed that only approximately 20% of the virus particles reacted with the anti-polymerase antibody, whereas most reacted with an antibody against the immunodominant G-H loop of the virus. In the presence of ammonium ions, the expressed polymerase degrades the RNA of the virus into molecules sedimenting at approximately 12 S, indicating that it can act as a hydrolytic as well as a polymerizing enzyme. Moreover, the RNA in trypsin-treated virus particles is degraded when incubated at 37 degrees C, suggesting that the cleaved 56-kDa protein still possesses hydrolytic activity. In addition, the anti-polymerase antibody, which inhibits the polymerase activity of the E. coli-expressed protein, also partially inhibits the hydrolytic activity of the previously described endonuclease of the virus particle, suggesting that this enzyme is identical with the polymerase or forms part of it.

Antibodies, Viral↗
PubMed1994

Function of minor polypeptides in foot-and-mouth disease virus and poliovirus.

Foot-and-mouth disease virus and poliovirus each contain several minor polypeptides, in addition to the four structural proteins. One of these, the viral RNA polymerase, can also act as a nuclease, hydrolysing the RNA and thus destroying viral infectivity. It is tightly bound to the RNA and may be the packaging signal for assembly of the particle.

Aphthovirus↗
PubMed1994

DNA technology and vaccines.

It has been 20 years since the concepts that are now embraced in the term recombinant DNA technology were first described. The technology has been used to design new vaccines, and one product--that for hepatitis B--has been in widespread use for almost a decade. Several other engineered vaccines have shown considerable promise in laboratory trials. Nevertheless, the potential of the approach is still to be realized. This article describes the principles that are involved in the design of these new vaccines, focusing on those for hepatitis B and rabies.

DNA, Recombinant↗
PubMed1994

Synthetic peptides and purified antigens as vaccines.

Molecular biology and, in particular, knowledge of the immune response at the molecular level provide the research community with the opportunity to design vaccines that will elicit the appropriate responses for many diseases. The critical issue is to identify the immune response that correlates with protection. It is remarkable how well the empirical approach has worked; it is essential, therefore, not to ignore the lessons to be learned from these successes. It is particularly essential that each disease and the immune response that affords protection be studied individually so that the appropriate responses can be induced.

Antigens↗