Polio vaccine and retroviruses.

In this paper we consider the main steps in the process of manufacture of oral polio vaccine and assess the probable clearance factor for HIV retrovirus at each step. We conclude that the processes employed would have eliminated retrovirus contamination for all practical purposes.

Karyology and tumorigenicity testing requirements: past, present and future.

At the present time, karyology and tumorigenicity are applied to primary, diploid, and continuous cell systems in an uneven and inappropriate manner, largely for historical reasons. It is a significant anomaly that such rigorous requirements are applied only to diploid cells when, of all three cell types, they represent the category with the least potential problems. During the 1992 presidential campaign in the U.

Viral safety of blood derivatives: an overview.

The causes of past accidental viral transmissions associated with blood derivatives are reviewed briefly, as are the safety procedures instituted in Europe on the basis of viral validation studies. A comprehensive five-class classification system for delineating viral risk according to source material and comparative viral safety is presented. Newly emerging viruses are briefly discussed in view of the viral safety of blood products.

Viral vaccines and residual cellular DNA.

The acceptability of viral vaccines manufactured in culture of continuous cell lines opened the way to a new technology of vaccine preparation. The large scale cultivation of continuous cell lines contributed greatly to the improvement of the safety and the consistency of viral vaccines. Experimental studies concerning residual cellular DNA and its oncogenic potential showed clearly that this material is not able to induce tumours.

Viral iatrogenic contamination and safety of biologicals.

The use of biologicals such as bacterial or viral vaccines have an inert risk as a result of their preparation. In the last century it was difficult to determine the correlation of the clinical accidents until the characteristic viral genome became available. Generally, the frequency of accidents provoked by viral vaccines has diminished due to (1) the improvements of the methods used for viral inactivation and purification, (2) the introduction of good manufacturing practices and rigorous regulatory policy and (3) the progress in the post-clinical surveillance of adverse reactions after vaccine administration, allowing a better risk-benefit analysis.

A view on regulatory aspects of live viral vaccine safety.

Regulatory requirements on live viral vaccines take into consideration their value in the improvement of public health in countries that have used them in large vaccination campaigns. However, since they have also been involved in clinical accidents, a careful assessment of their safety is necessary to establish the risk-benefit balance. From this point of view, live recombinant vaccines represent a new category of products and their future use in the field should be preceded by scientific debate concerning their safety and potency.

Albert B. Sabin and the development of oral poliovaccine.

There are many reasons for the modern interest in viral vaccines, but there is no doubt that the key role played by viral vaccines in public health is the major factor since other prophylactic or therapeutic anti-viral products simply do not exist. Viral vaccines have a long history that has been marked by successful events and by tragic accidents. Live viral vaccines are an extraordinary category of biologicals since, despite their reputed efficacy, they were developed by empirical experiments and patient epidemiological observation.

A mutation in the RNA polymerase of poliovirus type 1 contributes to attenuation in mice.

The attenuated Sabin strain of poliovirus type 1 (PV-1) differs from the neurovirulent PV-1 Mahoney strain by 55 nucleotide mutations. Only one of these mutations (A-480-->G, in the 5' noncoding (5' NC) region of the genome, is well characterized, and it confers a strong attenuating effect. We attempted to identify genetic attenuation determinants in the 3'-terminal part of the Sabin 1 genome including the 3D polymerase (3Dpol) gene and the 3' NC region.

Molecular characterization of mouse-virulent poliovirus type 1 Mahoney mutants: involvement of residues of polypeptides VP1 and VP2 located on the inner surface of the capsid protein shell.

Most poliovirus (PV) strains, including PV PV-1/Mahoney, are unable to cause paralysis in mice. Determinants for restriction of PV-1/Mahoney in mice have been identified by manipulating PV-1 cDNA and located on the viral capsid protein VP1. These determinants consist of a highly exposed amino acid sequence on the capsid surface corresponding to the B-C loop (M.

Analysis of neutralization-escape mutants selected from a mouse virulent type 1/type 2 chimeric poliovirus: identification of a type 1 poliovirus with antigenic site 1 deleted.

A chimeric type 1/type 2 poliovirus (v510), in which the antigenic site 1 (Ag1) of poliovirus type 1 (PV-1) Mahoney was replaced by the corresponding site of poliovirus type 2 (PV-2) Lansing, is known to be neurovirulent for mice and neutralized by both type 1 and type 2 monoclonal antibodies. Neutralization-escape mutants to monoclonal antibodies specifically recognizing the PV-2 sequence were obtained from v510. The nucleotide sequence and the mouse neurovirulence of mutants were determined.

European project concerning the guidelines on medicinal products derived from human blood and plasma.

The Biotechnology/Pharmacy Working Party (BPWP) decided in October 1989 to put on its working programme the elaboration of a guideline on medicinal products derived from human blood and plasma. This has been determined by the adoption of Directive 89/381/EEC extending the scope of the EEC pharmaceutical legislation to medicinal products derived from human plasma. Because Directive 89/381/EEC will come into force on 1 Jan.

Mapping of mutations associated with neurovirulence in monkeys infected with Sabin 1 poliovirus revertants selected at high temperature.

Poliovirus type 1 neurovirulence is difficult to analyze because of the 56 mutations which differentiate the neurovirulent Mahoney strain from the attenuated Sabin strain. We have isolated four neurovirulent mutants which differ from the temperature-sensitive parental Sabin 1 strain by only a few mutations, using selection for temperature resistance: mutant S(1)37C1 was isolated at 37.5 degrees C, S(1)38C5 was isolated at 38.

Poliovirus permissivity and specific receptor expression on human endothelial cells.

To test the role of the endothelial cells (EC) in the poliomyelitis pathogenesis, their sensitivity to poliovirus infection was determined at different times after isolation from the human umbilical vein. While 80% of EC were permissive for poliovirus after 4 days of in vitro primary cultures, only 6% of freshly isolated EC were susceptible to poliovirus infection. A progressive development of this susceptibility was observed during the first 3 days of culture.