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D Magrath

Publications and source records attributed to D Magrath.

18 recordsLinked to original sources

On the role of the World Health Organization in the development of Sabin vaccines.

The World Health Organization has played a major part in the development, surveillance and distribution of attenuated poliovirus vaccines. At a time when most of the United States' efforts concerned the introduction of Salk-type vaccines, WHO initiated studies that set standards and permitted the large scale trials of Sabin and other attenuated vaccines. Independent expert review validated studies in countries such as the U.S.S.R. which helped lead to the adoption of Sabin vaccines for worldwide usage. Surveillance by WHO Collaborative Centres established the safety of Sabin vaccines and identified issues of reversion primarily concerning type 3 viruses, initiating studies which have elucidated the molecular mechanism of reversion. Efforts by the Biological Unit of the World Health Organization have ensured worldwide acceptable standards to control the safety and manufacture of vaccines. Revision of neurovirulence test methods has ensured adequate safety testing of vaccine lots, reduced the costs of such studies and the numbers of primates needed, important ethical and conservation issues. Finally, the World Health Organization has played a major part in the worldwide supply of vaccines at affordable prices and has been the repository of, and had the exclusive license, to Sabin vaccines since 1972.

Animals↗

Studies on the attenuation of the Sabin type 3 oral polio vaccine.

The genetic basis of attenuation of the poliovirus type 3 vaccine strain P3/Leon 12a1b has been investigated by comparing the nucleotide sequence of this strain with that of its neurovirulent progenitor P3/Leon/37 and by constructing recombinants between these two viruses using infectious cDNAs. Preliminary results suggest that attenuation is caused by just two point mutations, one occurring in the 5' non-coding region and the other causing an amino acid change in coat protein VP3.

Base Sequence↗

Response of children to a single dose of oral or inactivated polio vaccine.

Approximately 200 children aged 8, 12 and 16 years with poliovirus neutralising antibody titres of less than 1/45 to at least one type were given a single dose of oral or inactivated polio vaccine. Almost all children given IPV responded with high levels of neutralising antibody to all 3 types. The response to the oral vaccine was less dramatic. The relationship between pre-existing antibody and the further response and the implications for susceptibility to reinfection will be discussed.

Adolescent↗

Studies on the characteristics of Poliovirus type 3. III. Strain characteristics after passage in man.

The markers d, IST, EA1(OH)3 and rct at sub- and supraoptimal temperatures as well as neurovirulence (PMic) for monkeys was determined for strains isolated from children vaccinated with Leon 12a1b vaccine, their contacts and from paralytic cases. The strains were isolated at early and late phases of excretion. The changes concerned mainly rct determined at supraoptimal temperatures, d and PMic markers, especially in strains isolated at the late phase of excretion. The passage through the human alimentary tract did not change such markers as IST and EA1(OH)3. Some degree of correlation was observed between the rct 40.3, d and PMic markers.

Animals↗

Studies on the characteristics of poliovirus type 3. II. Characteristics of "hot" clones.

Markers d, IST, EA1(OH)3, rct (at sub- and supraoptimal temperatures) and neurovirulence were determined for clones isolated from two lots (S2 and S3) of vaccines containing poliovirus strain Leon 12a1b. Changes of markers rct, d and neurovirulence were observed in several clones isolated from S2 vaccine. No changes were observed in IST and EA1(OH)3 markers.

Animals↗

Poliovirus crystals within the endoplasmic reticulum of endothelial and mononuclear cells in the monkey spinal cord.

The lumbar motor columns of a cynomolgus monkey that had become tetraplegic after experimental infection with a highly virulent strain of type 3 poliovirus were examined by electron microscopy. Crystalline aggregates of poliovirus occurred within the endoplasmic reticulum of endothelial cells as well as of mononuclear inflammatory cells. This finding suggests that the endoplasmic reticulum might be much more involved in poliovirus multiplication than has been previously supposed.

Animals↗