Experience with vero cells at Pasteur Mérieux Connaught.

The Vero cell line has been used by Pasteur-Merieux-Connaught (PMC) since 1982 with the Cell Bank's system to produce, at the 142nd passage, inactivated polio vaccine (IPV), oral polio vaccine (OPV) and rabies vaccines. The safety of the cell line has been regularly validated at the WCB level according to the WHO and European Pharmacopeia requirements for absence of bacteria, fungi, mycoplasma and viruses. Special emphasis was devoted to establishing the absence of simian viruses (SV40, SIV, Retro-D virus, simian CMV).

Experience with the Vero cell line.

The Vero cell line has been managed with the Cell Bank system to produce at the 142nd passage IPV, OPV and rabies vaccines since 1982 by Pasteur Mérieux Serums & Vaccins (PMsv). The safety of the cell line was regularly validated at the Working Cell Bank (WCB) level according to the WHO and European Pharmacopoeia requirements for absence of bacteria, fungi, mycoplasma and viruses. A special emphasis was devoted to research on the absence of simian viruses (SV40, SIV, Retro-D virus and simian CMV).

Comparative study of poliovirus excretion after vaccination of infants with two oral polio vaccines prepared on Vero cells or on primary monkey kidney cells.

A comparative study was designed to assess the bioequivalence of 2 oral poliovaccines (OPV) produced on 2 different cell systems: primary monkey kidney (PMK) cells and the Vero cell line. The Vero cell line has been used to overcome the problem of obtaining a regular supply of high quality monkeys that are devoid of latent viruses. For this study, 9 children were vaccinated with PMK-OPV and 12 children with Vero-OPV.

Computerized analysis of food records: role of coding and food composition database.

Reported dietary intake records of 30 subjects (26 men and 4 women) were analysed by three different centres using their own computerized nutrient database systems. The agreement between systems was evaluated by different statistical criteria (the correlation coefficient, the mean difference and the proportion of individuals placed in the same thirds of distribution). Significant differences between the three systems were found in the calculation of alcohol, polyunsaturated fatty acids, saturated fatty acids, linoleic acid, linolenic acid, cholesterol, magnesium, sodium and water.

Laser immunonephelometry reference intervals for eight serum proteins in healthy children.

Eight serum proteins were analyzed with the Behring nephelometer in samples from 479 healthy French children, ages three to 16 years. Girls had higher concentrations of IgM and albumin than boys had. Age appeared to be a main factor of variation for the proteins tested.

Improved distribution of antigenic site specificity of poliovirus-neutralizing antibodies induced by a protease-cleaved immunogen in mice.

Previous studies showed that the distribution of antigenic site specificity of neutralizing antibodies to type 3 poliovirus obtained with the inactivated poliovirus vaccine can be deficient as compared with that obtained following poliovirus infection. This observation was shown by the relatively low capacity of sera from inactivated-poliovirus-vaccine-immunized persons to neutralize poliovirus cleaved at antigenic site 1. We investigated possibilities for improving the situation in a mouse model.

Polio and rabies vaccines produced in continuous cell lines: a reality for Vero cell line.

The Vero cell line was applied to the production of Enhanced-Inactivated Polio Vaccine (E-IPV), Oral Polio Vaccine (OPV) and Rabies Vaccine, also called Purified Vero Rabies Vaccine (PVRV) for humans. The cell line was expanded through the cell bank systems. Using a microcarrier culture technique, a large-scale production combined with an efficient purification process was developed.

Retinol, beta-carotene and alpha-tocopherol status in a French population of healthy children.

The serum of 392 French healthy children aged 1-16 years was analysed for vitamin A, vitamin E, beta-carotene and cholesterol contents. The study group consisted in 185 females and 207 males, living in the area of Tours, France. The mean serum values are 42.

Lack of adjuvant effect of the pertussis component on IPV DTP-polio vaccine in children.

On day 0, four groups of children (3 to 6 months old) randomly received IPV alone or IPV + pertussis, or IPV + DP, or IPV + DTP. At days 28 and 56, all the children received the same IPV + DTP vaccine. Polio neutralizing and diphtheria antibodies were determined at days 0, 28 and 56.

Inactivated polio vaccine: industrial production from micro-carrier Vero cells culture.

In 1980, we presented our preliminary results of large-scale production of Inactivated Polio-Vaccine (IPV). The virus was produced by Vero cells culture grown on micro-carrier in 150 litre tanks; now we produce the poliovirus in 1000 litre tanks. All the tests certifying the 'Cell Bank' have been passed; the quality of purification procedure was demonstrated; additional clinical studies were done; this new reassessed IPV was licensed in France in July 1982.

Industrial-scale production of inactivated poliovirus vaccine prepared by culture of Vero cells on microcarrier.

In 1980, the authors reported preliminary results of large-scale production of inactivated poliovirus vaccine in which virus was produced in Vero cell culture on a microcarrier. For this first stage of development, 150-liter tanks were used. The virus is now produced in 1,000-liter tanks.

Thousand litre scale microcarrier culture of Vero cells for killed polio virus vaccine. Promising results.

Through the progress of scientific knowledge the Vero cell line was considered to be a suitable alternative cell substrate for the industrial production of Polio Virus. Using microcarrier culture, more than 10(12) cells could be obtained weekly for virus inoculation. The virus yield is around 60 D units/ml for type I; 20 D units/ml for type II, and 50 D units/ml for type III.

Angiotensin converting enzyme in bronchoalveolar lavage fluid in pulmonary sarcoidosis.

Alveolar angiotensin converting enzyme (ACE) and serum ACE were measured simultaneously in 16 patients with histologically confirmed sarcoidosis and in 16 control subjects. Although alveolar ACE was abnormally elevated in all 15 cases of active sarcoidosis, serum ACE was not. No correlations were found between radiographic staging of pulmonary sarcoidosis and the levels of these enzymes.

The large-scale cultivation of VERO cells in micro-carrier culture for virus vaccine production. Preliminary results for killed poliovirus vaccine.

As the increasing shortage of monkeys is a reality, the application of an alternative cell substrate for large-scale production of Killed Poliomyelitis Vaccine (KPV) was studied. Through progress of scientific knowledge the non-tumorigenic VERO cell line was considered to be a suitable alternative cell substrate for this purpose. The Master-Cell-Bank and Working-Cell-Banks prepared by us are giving a practically inexhaustible cell source.

Comparison of sensitivity of VERO cell line versus primary monkey kidney cells in the detection of residual live polio virus during and after inactivation.

Substitution of Primary Monkey Kidney (PMK) Cells by Monkey Cell Lines (MCL) for detection of residual live virus in poliovaccine control has been considered for various reasons. The sensitivity of VERO Cells versus PMK cells has been investigated. This study was done with poliovirus during and just after formalin inactivation.

[Acute myeloblastic leukaemia in the course of non-Hodgkin's lymphoma (author's transl)].

Five cases of acute myeloblastic leukaemia (AML) arising in the course of non-Hodgkin's lymphoma (NHL) are described. The initial lymphoma was nodular lymphoid poorly differentiated in 4 cases. All patients were under chemotherapy for at least 28 months, and 3 of them were irradiated.

Chemotherapy--radiotherapy association in Hodgkin's disease, clinical stages IA, II2A: results of a prospective clinical trial with 166 patients.

One hundred sixty-six patients with clinical stages IA, II2A Hodgkin's disease were treated between April 1972 and December 1976 with three courses of multiagent chemotherapy (methylchlorethamine, vincristine, procarbazine, prednisone) followed by mantle irradiation--excluding mediastinum for those with initial upper cervical presentation and absence of mediastinal involvement--or inverted Y radiotherapy. None had staging laparotomy. With a follow-up of 12--84 months, median 40 months, the overall survival is 93.

[Complications with rifampicin treatment: one case with anuria (author's transl)].

The authors report a new case of acute renal insufficiency with Rifampicin. They evoke the clinical background which is characteristic of these anuric tubular nephritis. They recall the different complications with Rifampicin to which they can be associated and the different mechanisms which can be at the origin of this affection as well as the difficulties to reveal them.

[A thoracic "stealing" vascular syndrome (author's transl)].

The authors report quite a remarkable observation of a thoracic "stealing" vascular syndrome, apparently a sequela of a previous pleural involvement. It was a patient with fainting fits in effort related to severe hemo-diversion of the sub-pleural vascular laci fed by several vascular pedicles coming from the internal mammary artery and several broncho-intercostal arterial vessels. Selective bronchial arteriography revealed these pedicles, enabling an important blood derivation in effort without corresponding venous return, with a phenomenon of low cerebral outflow; a series of embolisms in these pedicles enabled to obtain a valuable obliteration of the main ones with a complete disappearance of the clinical signs.