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T W Pay

Publications and source records attributed to T W Pay.

At least 19 recordsLinked to original sources
PubMed1992

Foot and mouth disease vaccine potency tests in cattle: the interrelationship of antigen dose, serum neutralizing antibody response and protection from challenge.

The use of tests in cattle remains the basis for evaluating the potency of foot and mouth disease (FMD) vaccines intended for use in cattle. To be able to compare different types of potency test it is essential to have a good understanding of how measurable responses in cattle to vaccination relate to one another. In this paper the interrelationships were examined of log antigen dose (V50), serum neutralizing antibody response (SN50), and protection from challenge (probit), following a single-dose primary vaccination. Estimates of the slopes for each of the three regressions were obtained and these, together with values described by other authors, were used to evaluate how well some of the potency tests for FMD vaccines matched up to Recommendations of the Office International des Epizooties made in 1975.

Animals↗
PubMed1992

A potency test method for foot and mouth disease vaccine based on the serum neutralizing antibody response produced in cattle.

A method is described for converting a mean serum neutralizing antibody titre after primary vaccination directly into a percentage protection value using a single regression slope. This has advantages over the indirect method in which a potency value is first estimated on the log antigen dose scale before conversion to a percentage protection value, since to do this requires the use of three separate regression slopes. Test designs for the serological method have been formulated that meet the 1975 Recommendations of the Office International des Epizooties, and which possess minimum potency standards at least as high as those of the European Pharmacopoeia's vaccine dose extinction endpoint method.

Animals↗
PubMed1987

Sources of variability in foot and mouth disease vaccine potency estimates based on serum neutralizing antibody assay.

Some vaccines can be assayed for potency by measuring the serum antibody response they produce in vaccinated test animals. Using data obtained from potency assays on batches of foot and mouth disease vaccine, the sources of variability in such a method were examined. A linear model is proposed for the analysis of replicate serum neutralizing antibody assays, which represents an improvement on the usual approach of working with only a mean serum assay value for each test animal. Components of variance were calculated, allowing the relative importance of the numbers of test animals, or the numbers of serum assays per test animal, to be estimated in terms of the variability of the overall group mean antibody response. A method is described for calculating fiducial intervals for the serological potency estimates, and it is shown that these intervals are no larger than, and are in fact probably smaller than, those obtained from quantal challenge tests. The results have important implications for the design and analysis of similar biological tests used for other products.

Analysis of Variance↗
PubMed1987

Correlation of 140S antigen dose with the serum neutralizing antibody response and the level of protection induced in cattle by foot-and-mouth disease vaccines.

An analysis was made of data from potency tests on fifteen batches of monovalent foot-and-mouth disease vaccine, comprising five batches each of type O, type A and type C. Regressions were calculated for the relation of percentage protection (probit) versus log 140S antigen dose and for the serum neutralizing antibody titre (log SN50) versus log 140S antigen dose. Type O vaccines required a far higher level (220 ng) of 140S antigen to achieve a 50% protection level (PA50) in cattle than did type A (2.4 ng) and type C (4.36 ng) vaccines. Type O antigen, dose for dose, was as effective at provoking neutralizing antibody as the types A and C antigens. Thus, it would appear that a far higher log SN50 value (2.14) was required for type O vaccines to equate with 50% protection of cattle than was required for type A (1.17) and type C (1.41) vaccines. Prior to 1977, however, the PA50 value for type O vaccine strain was only 1.34 and it was concluded that an antigenic shift was the most likely cause for the large difference between that value and the current PA50 value.

Animals↗
PubMed1986

The use of serum neutralizing antibody assay for the determination of the potency of foot and mouth disease (FMD) vaccines in cattle.

The Permanent Commission of O.I.E. on foot and mouth disease has proposed a series of potency standards for foot and mouth disease vaccines. No totally in vitro assay has yet been developed to satisfy these requirements, and most Control Authorities require a potency assay to be carried out in cattle using challenge with virulent virus. There are various reasons why challenge tests should be replaced by serological tests, but a stumbling block to this is the requirement that the 50% protective antibody level (PA50) is valid only for a specific combination of vaccine virus seed lot with cattle virus seed lot in a laboratory. The results of challenge and antibody tests for 38 U.K. Control Authority vaccine batch tests were analysed to examine the correlation between potencies measured by the two methods. The correlation between the methods was high and the proportion of misclassification of batches was low. It is suggested that the results provide a good basis for future use of the serological method, but that it is still sometimes necessary to carry out challenge tests.

Animals↗
PubMed1985

The use of BHK suspension cells for the commercial production of foot and mouth disease vaccines over a twenty year period.

The Wellcome Foundation Ltd first used BHK suspension cells for the commercial production of foot and mouth disease vaccine in 1964. Since that time both the scale of operation and the volume of production has increased dramatically and in 1983 the Wellcome Group produced almost 350 million monovalent equivalent doses of vaccine from just over 2 million litres of antigen. Experience gained during this period has shown that with careful attention to plant design and operation this large industrial scale tissue culture process can be managed reliably and efficiently. Data will be presented to show the level of production and success rate achieved in our Foot and Mouth Vaccine production units together with an analysis of antigen yields and the comparatively few failures experienced.

Animals↗
PubMed1985

Production of rabies vaccine by an industrial scale BHK 21 suspension cell culture process.

A process for the production of an inactivated rabies vaccine for animal use is described, whereby the LEP Flury strain of rabies virus is grown in 1 000 L cultures of BHK 21 suspension-adapted cells. The virus is inactivated with aziridine and, after concentration and purification by hollow fibre ultrafiltration, is adsorbed onto aluminum hydroxide gel. The BHK 21 suspension-adapted Master Cell Seed used has satisfied all the requirements of the US Code of Federal Regulations, Title 9, (1977) for cell lines. Cultures prepared from it produce high yields of rabies virus antigen and vaccines with an average potency of 6 IU can be produced without difficulty. Such vaccines give at least 3 years' protection in dogs and are safe to use in all species. Experience gained with the closely analogous process for the production of FMD vaccines suggests that the process can be readily transposed and successfully operated in developing countries if and when it becomes cost-effective to do so.

Animals↗
PubMed1984

Graphical method for comparative statistical study of vaccine potency tests.

Producers and consumers are interested in some of the intrinsic characteristics of vaccine potency assays for the comparative evaluation of suitable experimental design. A graphical method is developed which represents the precision of test results, the sensitivity of such results to changes in dosage, and the relevance of the results in the way they reflect the protection afforded in the host species. The graphs can be constructed from Producer's scores and Consumer's scores on each of the scales of test score, antigen dose and probability of protection against disease. A method for calculating these scores is suggested and illustrated for single and multiple component vaccines, for tests which do or do not employ a standard reference preparation, and for tests which employ quantitative or quantal systems of scoring.

Vaccines↗
PubMed1984

Some applications of a graphical method for the comparative statistical study of vaccine potency assays.

Using examples drawn from some commonly-used methods for vaccine potency assay, we show how a graphical method of representing three key characteristics, precision, sensitivity and relevance, can be used to compare basic methods and variations in test design. We suggest that this method can be of considerable value to Control Authorities in establishing test designs and potency standards, and to vaccine manufacturers in formulating vaccines which will have a high probability of meeting these potency standards.

Animals↗
PubMed1979

Stability and immunogenicity of empty particles of foot-and-mouth disease virus.

Three strains of foot-and-mouth disease virus were shown to contain significant amounts of naturally occurring 75S, empty particles as well as the infectious, 140S full particles. One of these strains--A Pando (1970)--was studied in detail. The empty particles from this virus strain were shown to have an observed sedimentation coefficient of 67S in 0.04 M phosphate buffer; they were labile in SDS, non-infectious and probably RNA-free and, on heating, they broke down to 12S subunits as did the 140S particles. The empty particles differed from the full particles in their polypeptide composition since they contained VP0, but there was no evidence for a diminished content of VP4. The 75S particles were shown to be present in significant amounts and to be stable to AEI inactivation. At 4 degrees C they were stable for at least two years. In guinea pigs they were as immunogenic as the 140S particles. The antisera raised against the 75S particles had the same serological specificity in neutralization tests as sera prepared against the 140S particle. It was concluded that the 75S particles from the A Pando (1970) strain of FMD virus may provide as important a contribution as 140S particles to the immunogenicity of inactivated vaccines prepared from this virus strain.

Antigens, Viral↗
PubMed1978

Dose-response relationships in a microneutralization test for foot-and-mouth disease viruses.

Two-dimensional quantal microneutralization tests on foot-and-mouth disease viruses, in which neutralizing antibody activity was titrated against a serial range of virus doses, demonstrated a variety of dose-response curves some of which were rectilinear, others clearly curvilinear. Moreover, in the case of the non-linear responses obtained with some antisera, the shape of the curve was such that antibody titres recorded with doses of virus ranging from 10(3)-10(5) TCD50 were closely similar. Studies were carried out on the effect of varying the conditions of the test on the shape of the dose-response curve: significant differences were obtained after treatment of the antiserum-virus mixtures with anti-species globulin, and when the test was assayed in cells of differing susceptibility to infection.

Aphthovirus↗
PubMed1978

Microneutralization tests for serological typing and subtyping of foot-and-mouth disease virus strains.

A microneutralization test for serotyping of FMD viruses is described. It is based on earlier observations by Booth, Rweyemamu & Pay (1978) that dose-response relationships in quantal microneutralizations often deviated from linearity. The typing test described therefore utilizes undiluted virus preparations. In about 90% of samples a positive typing was obtained in contrast with about 50% for the complement fixation test. The test was also found to be susceptible to minimal quantities of heterotypic viral contamination. For strain differentiation the microneutralization test was carried out as a checkerboard test. When compared with the complement fixation test it was found to be more specific. The necessity to utilize virus-neutralization test systems for comparing FMD virus strains particularly for the purpose of vaccine selection is emphasized. The two dimensional microneutralization test has been applied to a study of comparing FMDV vaccine strains for Europe, South America, the Middle East and East Africa.

Aphthovirus↗
PubMed1977

Neutralization kinetics studies with type SAT2 foot-and-mouth disease virus strains. 1. Factors that influence the rate and pattern of neutralization.

A study of the kinetics of inactivation of foot-and-mouth disease virus type SAT 2 strains revealed that in most cases the rate of neutralization was not rectilinear. Deviations from first-order kinetics observed represented biphasic or parabolic and stepwise reactions. The initial rate was rapid and showed no lag phase or shoulder. The effects of deviations from linearity could be minimized by dilution of antiserum to a suitable extent. Treatment of virus-antibody mixtures with anti-species globulin resulted in enhancement of the rate of neutralization of homologous and heterologous reactions without significantly altering the relation between the two. This treatment also considerably reduced the amount of the persistent fraction. In attempt to disaggregate virus it was observed that sodium dodecyl sulphate inhibited neutralization of virus by specific antiserum.

Antibodies, Anti-Idiotypic↗
PubMed1977

Neutralization kinetics studies with type SAT 2 foot-and-mouth disease virus strains.

A comparison of homologous and heterologous rates of neutralization demonstrated that antigenic relationships of foot-and-mouth disease virus strains could be differentiated quantitatively by the kinetics of neutralization method described previously (Rwysed this way gave R values which were similar to those obtained with other neutralization test methods but which were generally smaller than those obtained with complement fixation test results. It was demonstrated that there were wide differences between the vaccine strains tested as demonstrated by R value relationships. An examination of r values, however, demonstrated that antisera to the Moz 1/70 strain were highly reactive with most of the virus strains from Central and Southern Africa. The selection of FMD virus strains with a wide serological range for vaccine production is discussed.

Animals↗
PubMed1975

The evaluation of hypersensitivity tests in cattle after foot-and-mouth disease vaccination.

The response to passive cutaneous anaphylaxis, dermal hypersensitivity and intravenous provocation tests has been compared in 30, 40, 31 and 24 cattle injected with foot-and-mouth disease vaccine 0, 1, 2 and 3 times respectively, using vaccine components and other substances as test materials. Reaginic antibodies demonstrated by passive cutaneous anaphylaxis in goats, were directed against BHK 21 cell extracts (20), hydroxypropylmethylcellulose (3) and an unidentified vaccine component (3), and distributed in 0, 5, 19 and 75 per cent of the cattle vaccinated 0, 1, 2 and 3 times. None of the animals showed clinical signs of allergy after vaccination. When BHK 21 cell extract was injected intradermally a significant correlation was noted between the development of large weals and the presence of reagins although the size of the weals was not correlated with the reagin titres. In the case of hydroxypropylmethylcellulose a similar trend was evident. The majority of cattle with large dermal weals possessed reagins but the number of reactions was too small for statistical evaluation. Dermal reactions to sodium penicillin, sodium carboxymethylcellulose, saponin and whole vaccine occurred in both unvaccinated and vaccinated cattle but BHK 21 cell lysate and normal bovine serum provoked weals which increased in frequency according to the number of vaccinations experienced. Intravenous hydroxypropylmethylcellulose elicited a response in all the animals previously injected with certain batches of vaccine but cell extract intravenously produced a clinical response in half the tested animals which was uncorrelated with the results of the passive cutaneous anaphylaxis or dermal hypersensitivity tests.

1-Propanol↗