Contamination Of Vaccines Research Articles

Human papovavirus, BK strain: biological studies including antigenic relationship to simian virus 40.

Some of the properties of a new human papovavirus, BK, have been examined. Host range studies of BK virus (BKV) showed human cells to be more sensitive to infection than monkey cells; human fetal brain cells appear to be highly sensitive to BKV, with the production of extensive cytopathology characterized by cytoplasmic vacuolization. The hemagglutinin of BKV is associated with the virion and is resistant to ether or heating at 56 C for 30 min. Fluorescent antibody as well as neutralization tests indicated antigenic similarities between simian virus 40 (SV40) and BKV. Cells undergoing lytic infection with BKV synthesized intranuclear T antigen(s) which reacted with SV40 T antibody demonstrable by immunofluorescence. However, BKV did not appear to induce SV40 transplantation antigens in transplantation-resistance tests. Evidence was obtained that BKV was present in humans prior to the widespread use of polio vaccines, thus ruling out the possibility that BKV is an SV40-related monkey virus, introduced into the human population by accidental contamination of poliovirus vaccines.

Sensitization against calf serum proteins as a possible cause of allergic reactions after vaccination

Sera from patients with typical cutaneous or general allergic reactions and other complaints after application of non-infectious smallpox vaccine have been examined for precipitating antibodies against calf serum and its albumin- or globulin-fraction respectively. Out of 12 patients with typical allergic reactions resembling Arthus-phenomenon or serum sickness, sera from seven of them reacted positively against whole serum and all but one of these to serum globulin. Also, no such antibodies were detected in a group of persons with less typical clinical signs. No antibodies against host tissue or the virus contained in the vaccine were detected by the microtechnique used, antibodies against calf serum albumin were found only in one patient. The possible role of calf serum contamination of viral vaccines for evoking allergic reactions in sensitized persons is discussed briefly.

Calf serum content of various viral vaccines and possibilities for its reduction

A total of 26 inactivated or live virus vaccines obtained from different sources and prepared on different cell cultures were examined, by a semiquantitative procedure of immunoprecipitation, for their concentrations of calf serum albumin and calf serum globulin. The highest serum protein concentrations (≈ 2 to > 10 μg/ml) were found in single (first) harvest vaccines from large enveloped viruses. The serum content of single harvest vaccines from small, naked viruses was intermediate (< 1–2 μg/ml) and lowest for multiple harvest or single second harvest vaccines (usually < 1 μg/ml). Using a similar evaluation system the effectiveness of different washing and refeeding procedures for the removal of serum proteins from cultures of permanent monkey cells was studied. The conventional washing procedures proved rather ineffective even if the washing fluid was kept on the cells for a prolonged period. Serum proteins could be almost completely removed only by refeeding the cell cultures once for 24 h with serum-free medium. It was concluded from these results that serum proteins (especially the globulin fraction) are adsorbed onto the cells and possibly also onto the surface of larger, enveloped viruses and are not completely removed by the conventional washing procedures. The importance of the contamination of vaccines with residual calf serum for evoking allergic reactions and the possibility of eliminating such serum from vaccines are discussed briefly.

Chick embryo lethal orphan (CELO) virus as a possible contaminant of egg-grown virus vaccines.

SUMMARYThe inactivation kinetics of CELO virus were studied in the presence of 1/4000 formaldehyde. Inactivation of the virus by formaldehyde at 4° C. was not complete after 14 days incubation. Formaldehyde inactivation at 36° C., however, was rapid and no virus was detected after 24 hr. incubation.Neutralizing antibody to CELO virus was detected in 20–88% of sera tested from five flocks of hens. This suggested dissemination of the virus in England and Scotland. However, no CELO virus neutralizing antibody at a serum dilution of 1/8 was detected in 142 normal human sera or in 229 sera from persons who had been immunized with egg grown, inactivated influenza virus vaccine.We would like to thank Professor C. H. Stuart-Harris and Drs J. E. Wilson, D. A. Martin and D. Breeze for their help and their criticisms of the manuscript.Dr G. C. Schild kindly supplied a number of the human sera used in the study. The study was financed in part by the National Fund for Research in Poliomyelitis and other Crippling Diseases and by the British Empire Cancer Campaign.

Mycoplasma gallisepticum in a Commercial Laryngotracheitis Vaccine

The vertical transmission of Mycoplasma gallisepticum has been well documented. The possibility that egg-propagated vaccines could become contaminated with this organism has been recognized for some time (6). The finding by Conrad (2) in 1958, that a portion of the avian Mycoplasma population in egg yolk survives lyophilization tended to substantiate the possibility of vaccine contamination. In 1962 and again in 1965, study groups (8,9) on avian Mycoplasma infections recommended "that all eggs used in the production of poultry biologics . . . be obtained from flocks free of M. gallisepticum." While bacterial contamination of poultry vaccines has been demonstrated (3,12), Oshel and Gourlay (7) did not detect antibodies against Mycoplasma gallisepticum using 55 serial lots of Newcastle disease, infectious bronchitis, or combination Newcastlebronchitis vaccines inoculated into the posterior thoracic air sac of two-week-old chicks.

Detection of Bacterial Contaminants in Live Virus Poultry Vaccines

VER 2 billion doses of live virus poultry vaccines are produced annually. Embryonated eggs used in manufacture of these vaccines, when contaminated, can be a means of contaminating vaccines. Although Federal regulations5,6 exist for testing of these vaccines they do not appear adequate. Johnson et al.4 and others1,7 have brought out the importance and need for additional testing standards. Such standards should have as their goal the eventual establishment of Federal regulations requiring sterility of poultry vaccines. Membranes of cellulose derivatives for bacterial analyses were introduced into the United States by Goetz2 and are now used widely in water and dairy sanitation. Holdowsky,3 applied the membrane filter technic to sterility testing of antibiotic preparations. This technic with certain modifications was investigated for its applicability and compared to the agar plate method for detecting bacterial contaminants in experimental and commercial live virus poultry vaccines. Little work has been done to determine if contaminated vaccines exist industry wide; whether antibiotics added during preparation of the vaccines completely eliminate bacterial