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D I Magrath

Publications and source records attributed to D I Magrath.

35 records · Page 2Linked to original sources

Genetic and antigenic variation in type 3 polioviruses: characterization of strains by monoclonal antibodies and T1 oligonucleotide mapping.

Considerable genetic and antigenic heterogeneity was detected among a collection of 17 poliovirus type 3 strains isolated between 1939 and 1958 in studies using monoclonal antibodies and by T1 oligonucleotide mapping. Heterogeneity was detected even amongst a collection of nine viruses designated Saukett and assumed to originate from the same prototype virus. The monoclonal antibodies were found to differ in their strain specificities for poliovirus type 3 strains in virus neutralization or single-radial-immunodiffusion tests. Relationships between strains detected in this way were in general consistent with those detected by oligonucleotide mapping. One of the monoclonal antibodies (NIBp 56) was able to distinguish between certain Saukett virus strains which differed by as little as a single specific oligonucleotide. The heterogeneity detected amongst Saukett viruses is of potential practical importance since these strains are used widely in the manufacture of inactivated poliovirus vaccine.

Antibodies, Monoclonal↗

Characteristics of single-radial-diffusion and autoradiographic zone size enhancement (ZE) techniques for poliovirus antigens.

The reactions of polioviruses in single-radial-immuno diffusion (SRD) tests were investigated with a view to developing accurate and sensitive antigen assay systems. In direct SRD tests, employing high concentrations of immune poliovirus serum in agarose gels, poliovirus D antigens produced D antigens produced clear reaction zones demonstrated by protein staining. The reactions were type specific for polioviruses of types 1, 2 and 3 but the tests were of low sensitivity being applicable only to the assay of virus concentrates. A novel autoradiographic zone size enhancement (ZE) test was developed which increased the sensitivity of the SRD assay 40--100 fold. The ZE test was dependent upon the ability of unlabelled poliovirus to co-migrate with the radioactive marker virus and so enhance the zone-size detected autoradiographically. The areas of the autoradiographic zones were directly proportional to the concentration of unlabelled antigen. The ZE test was capable of detecting poliovirus D antigens in diluted cell culture fluid harvests in amounts corresponding to 103.3 - 104.3 TCD50 of infectious virus.

Animals↗

Immunoassay of poliovirus antigens by single-radial-diffusion: development and characteristics of a sensitive autoradiographic zone size enhancement (ZE) technique.

The reactions of polioviruses in single-radial-immunodiffusion (SRD) tests were investigated with a view to developing accurate and sensitive antigen assay systems. In direct SRD tests, employing high concentrations of immune poliovirus serum in agarose gels, poliovirus D-antigens produced clear reaction zones demonstrated by protein staining. The reactions were type-specific for polioviruses of types 1, 2 and 3 but the tests were of low sensitivity, being applicable only to the assay of virus concentrates. A novel autoradiographic zone size enhancement (ZE) test was developed which increased the sensitivity of the SRD assay 40- to 100-fold. The ZE test was dependent upon the ability of unlabelled poliovirus to co-migrate with the radioactive marker virus and so enhance the zone size detected autoradiographically. The areas of the autoradiographic zones were directly proportional to the concentration of unlabelled antigen. The ZE test was capable of detecting poliovirus D antigens in diluted cell culture fluid harvests in amounts corresponding to 10(3.3) to 10(4.3) TCID50 of infectious virus. Studies with poliovirus type 3 strains indicated that the ZE test was narrowly strain-specific for the D-antigen of poliovirus type 3 strains when homologous type 3 D-antigen was used as radioactive marker, but broadly cross-reactive for the D-antigen of type 3 viruses when heterologous poliovirus type 3 D-antigen was used as marker.

Antigens, Viral↗

Immunity of children to diphtheria, tetanus, and poliomyelitis.

A survey of titres of diphtheria and tetanus antitoxins and of antibodies to polioviruses in the sera of 291 schoolchildren aged 15, 11, and 7 years showed that high immunisation rates can evoke protective concentrations of tetanus antitoxin in 98% of children and protective levels of the antibodies to diphtheria and all three types of poliomyelitis in 85% of children. Reinforcing immunisation at school entry appeared to be necessary to maintain adequate titres of diphtheria antitoxin in children up to 15 years of age, not essential to maintain adequate titres of tetanus antitoxin, and to have little effect on the titres of antibodies to poliomyelitis.

Adolescent↗

WHO collaborative studies on poliovirus type 3 strains isolated during the 1968 poliomyelitis epidemic in Poland.

In 1968 in Poland an extensive outbreak of poliomyelitis, caused by type 3 poliovirus, began about four months after small vaccine trials with the Leon 12a(1)b (Sabin) and USOL-D bac vaccine strains had been carried out. Because of the temporal association, and because the first cases appeared in the province in which the USOL-D vaccine trial was carried out, a detailed investigation of the strains isolated from cases in the epidemic was made in four laboratories in an attempt to determine whether they were related to the two vaccine strains or to a "wild" strain. All the studies were made under code. The rct marker was of no help in determining the relationship of the epidemic strains to the vaccine strains. The McBride test and the elution marker test clearly separated the Leon 12a(1)b strains from those from the cases, but were incapable of detecting whether the epidemic strains were related to the USOL-D bac strain or to wild type 3 strains. Thus the studies did not provide valid information on the origin of the epidemic.

Child↗

Antigenic characterization of poliovirus type 3 using monoclonal antibodies.

Hybridoma cell lines secreting monoclonal antibodies to type 3 poliovirus were prepared, and their reactivity with infectious virus (D antigen), empty particles (C antigen), and isolated virion capsid proteins ( VPs ) were examined. Eight antibodies reacted with epitopes common to D and C antigens, and all of these possessed high titers of neutralizing activity. However, only 12 of 19 antibodies that reacted exclusively with D antigen neutralized virus infectivity, and some of these reacted only with strains of virus with T1-oligonucleotide maps identical or similar to that of Sabin vaccine polio virus. These antibodies will be of value in identifying strains of virus derived from Sabin vaccine. None of the 20 monoclonal antibodies that neutralized type 3 poliovirus strains reacted in immunoblot experiments with isolated virion capsid proteins. However, six of the 24 antibodies that reacted only with noninfectious C antigen bound to VP1 and VP3, and three of these antibodies also reacted with proteins of poliovirus types 1 or 2. The lack of reactivity of neutralizing monoclonal antibodies with isolated viral proteins suggests that the antigenic properties of proteins are determined by their arrangement in the virus and not simply by amino acid sequence.

Animals↗