Attenuation of Rubella Virus by serial Passage in Primary Rabbit Kidney Cells: III. Clinical Trials in Infants

Abstract

ExtractHigh passage Cendehill strain of rubella virus, possessing in vivo and in vitro characteristics of an attenuated virus, was tested for efficacy in 28 seronegative infants, 3 to 23 months old. Thirteen seronegative infants received one subcutaneous injection of 0.5 ml of the vaccine preparation containing 10 3 -7 plaque-forming units (PFU) per ml. Fifteen seronegative infants served as controls for viral spread and were kept in intimate contact with the vaccinees for a period of 6 weeks.All thirteen vaccinees developed high levels of hemagglutination-inhibiting antibodies, from V128 to VaiMs, confirming the immunogenicity of the vaccine. No clinical reactions were observed in the vaccinees. The fifteen contacts remained seronegative, indicating that no viral spread occurred from the vaccinees to the susceptible contacts.The present clinical trial provides evidence that high-passage Cendehill strain presents characteristics of immunogenicity, nonreactogenicity and noncommunicability, making it a prospective candidate for a live attenuated rubella virus vaccine. SpeculationWhen the results of preliminary immunization trials with the attenuated Cendehill strain of rubella virus are confirmed in larger groups, this strain may meet all the criteria required for a safe and efficient immunizing agent against rubella.

Clinical and Laboratory Studies with Rubella Vaccines in Adults

“…None of the symptoms, either arthralgia or adenopathy, were severe enough to interfere with the daily activity of those participating, and it was the general consensus of opinion of all who took part in these trials that these vaccines were certainly acceptable. These reactions, mild though they were, were slightly more noticeable than in previous reports (Lepow et al, 1968;Du Pan et al, 1968a. This could be related to age, as all the volunteers were adults and clinical manifestations of natural rubella are generally more noticeable in adults than in children.…”

“…At first sight these titres, which are about four times lower than those usually found in patients convalescent from rubella, are somewhat lower than those reported by Du Pan et al (1968a) andMeyer et al (1968), but it does not seem profitable at this stage to compare titres obtained in different laboratories. The technique for measuring haemagglutination-inhibition antibody varies from one laboratory to another as does the interpretation of the titres, and more especially because there is as yet no international reference serum.…”

“…Lack of transmission could be simply due to the process of attenuation. There is evidence that some attenuated strains show a lack of infectivity for the nasal mucosa (Du Pan et al, 1968a), and earlier observations by Meyer et al (1967) showed that the attenuated HPV-77 strain was of reduced virulence in pregnant monkeys and did not cross the placenta. This is the crux of the question so far as human beings are concerned, as the ultimate test of safety of a vaccine strain is that, even if the virus does cross the placenta, it should be non-pathogenic for the foetus.…”