Behaviour of five commercial measles vaccines in an accelerated stability test.
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Biomedical subjects
Publications and source records attributed to J Peetermans.
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Two recombinants (R22 and R75) of the attenuated B/USSR/69 strain Bright and the virulent B/Hong Kong/5/72 and one recombinant (R5) of Bright and the virulent B/Hong Kong /8/73 were selected for genotypic and phenotypic caracterization. All three recombinants had the growth property of the attenuated parent Brigit. Analysis of their RNA's by polyacrylamide gel electrophoresis revealed that, the strains R22 and R75 had derived all their genes from Brigit, those coding for haemagglutinin excepted. These recombinants were clinically evaluated and found to be attenuated and immunogenic. The recombinant R5 which derived, besides the bene coding for the haemagglutinin, several other genes from B/Hong Kong/8/73 was only partly attenuated since it induced influenza-like symptoms in one out of three volunteers. It is concluded that the strain Brigit can be used as a donor of genes for the attenuation of the B/Hong Kong/5/72 virus and that recombinants of influenza type B can be identified, like influenza type A recombinants, by their RNA pattern.
The application of photon correlation spectroscopy for the evaluation of motility parameters of undiluted human sperm is investigated. Measurements on semen samples, selected visually as good (i.e., fraction motile spermatozoa larger than 0.6 and a positive appreciation of the motion), gave estimates of the fraction motile spermatozoa, reproducible within 10%, and of the mean velocity of the motile cells, reproducible within 5%.
In 1967-1968 a trial of "Cendehill strain" rubella vaccine was initiated in a group of 3 to 22 year-old prescreened seronegative girls, most being between 8 and 16 years of age. Sera from the vaccinees were taken at regular intervals during a period of 8 to 10 years. The evolution of the antibodies was followed over this period. No antibody titer change was observed in 75 to 78% of the sera. A four fold increase was shown in 6 to 10% and a four fold decrease in 15% of the vaccinees. All sera still showed a positive titer at the end of the period. The importance of these results for the final objective of rubella vaccination will be discussed.
The stability of the titer of live vaccines is a very important factor for successful immunization, especially in countries with a hot climate. For the freeze-dried vaccine, the results of stability tests show that the second generation Rimevax possesses the desired resistance to thermodegradation. In the refrigerator, the shelf life is at least 2 years. Exposure at 20--25 degress C for 1 month, at 37 degrees C for 7 to 14 days or at 41 degrees C for 3 to 7 days results in a vaccine retaining its full immunogenic activity. The value of an accelerated stability test at 37 degrees C for 7 days for the prediction of the potency of each lot is proven. This test should be part of the minimum requirements for live vaccines. The potency of reconstituted measles vaccines is evaluated. Rimevax shows a remarkable stability at higher temperatures. At 37 degrees C, the immunogenic activity is retained for 2 to 3 hours. Reconstitution with diluent at 41 degrees C and subsequent exposure to this temperature does not affect the titer significantly during the first half hour. The comparison of published stability data of measles vaccines shows that Rimevax is one of the most thermoresistant preparations.
The Alice strain of live attenuated influenza virus was obtained by selection of a gamma inhibitor-resistant strain from a virus recombinant between A/PR/8/34 (HON1) and A/England/42/72 (H3N2). Its behaviour in vitro and in vivo was studied. Three marker systems were investigated: resistance to serum inhibitors, growth capacity at high temperature and low sensitivity to amantadine hydrochloride. In ferrets the strain was found to be attenuated and immunogenic. Passages in man, animals and eggs have not affected its resistance to gamma inhibitors.
Stability of live, freeze-dried vaccines is a major factor for successful vaccinations. Vaccines may be stored at -20 degrees C or less for long periods without loss of activity and this storage does not affect stability during subsequent storage. Storage in the refrigerator for long periods is harmless for certain very stable vaccines such as influenza, rubella, NDV, Marek's. Other vaccines, such as IBV, show a significant loss in titer after 2 years. The routine use of an accelerated stability test, e.g. exposure of each lot manufactured to 37 degrees C during 7 days, provides useful information regarding the stability of the vaccine at +4 degrees C. In general the loss during the accelerated stability test is higher than the loss after 24 months storage in the refrigerator. Specifications requiring that each vaccine lot must possess, after the accelerated test, a titer equal to or higher than the minimum titer needed for immunization, are a guarantee of sufficient potency at the time of administration. To solve the problems in tropical countries stable vaccines are essential. Cendevax and Rimevax exposed to tropical temperatures still possess the minimum required titer after several days.
The immune responses in volunteers vaccinated intranasally with a live influenza virus vaccine containing attenuated A and B strains have been studied. The hemagglutination-inhibiting antibody titers for both components were determined a few weeks after vaccination. They demonstrated that a good antibody response had been induced in a high percentage of volunteers. The hemagglutination inhibiting titers and percentage of seroconversion for both components were comparable to the results obtained after the intranasal administration of each component separately.
Triple seronegative calves were exposed by the nasal route to three (ts) mutants of bovine respiratory viruses (PI3, IBR, Adeno3). After a single exposure, they responded with significant levels of serum antibodies to the three viruses. Nasal antibodies were demonstrated for PI3 and adenovirus antigens. The failure to demonstrate nasal antibodies to IBR may be due to lack of sensitivity of the procedure used. When reexposed six weeks later, calves had sharp increases in levels of serum antibodies and developed a secondary type response at the local level for all three viruses. The persistence of the local antibodies was much longer after reexposure than after primary inoculation. This study indicates that the simultaneous application of these three (ts) viruses by the respiratory route is perfectly safe and affords a long lasting immunity towards homologous respiratory infections.
A live attenuated influenza virus ("Ann" strain) derived from A/England/878/69 was given intranasally to a group of volunteers, most of whom had already circulating antibodies against H(3)N(2) viruses at the time of inoculation. There was a fourfold or higher increase of circulating hemagglutination-inhibiting antibodies in those volunteers who had relatively low initial titers. The response was lower in those with initially higher serum titers. The pattern of the serum neutralizing antibody response was very similar. The geometric means of the antineuraminidase antibodies were 67 and 118 pre- and postvaccination, respectively. All subjects showed a rise in local neutralizing antibodies in their nasal secretions with geometric means of 4 and 17 pre- and postvaccination, respectively. The levels of local antineuraminidase antibodies also rose in most subjects. In addition to the response to the homologous virus type, the antibody formation to the recent A/England/42/72 was measured in the sera and nasal secretions of some subjects. There was a clearcut response in most of the sera and in all of the secretions examined. The stimulation of circulating lymphocytes was measured in 6 volunteers. All volunteers showed a temporary stimulation. The stimulation index ranged between 2.5 and 28.5.
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