Failure of live, attenuated oral rotavirus vaccine.
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Biomedical subjects
Publications and source records attributed to G Zissis.
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Heterologous live, oral rotavirus vaccines of rhesus monkey (RRV-1) and bovine (RIT 4237) origin were tested for immunogenicity, excretion of virus, and clinical reactions in six- to eight-month-old infants. Antibody response, indicating infection with the vaccine virus, was detected in 21 (88%) of 24 children receiving the RRV-1 vaccine and in 18 (75%) of 24 receiving the RIT 4237 vaccine. Excretion of virus in the stools within one week after vaccination was demonstrable in 84% of the RRV-1 and in 21% of the RIT 4237 vaccinees. RRV-1 vaccination was associated with a febrile response (over 38 C) that clustered on days 3 or 4 postvaccination in 64% of the recipient children. In addition, 20% of the RRV-1 vaccinees had watery stools on days 4 or 5. Fever on days 3 and 4 and loose stools were not seen in the RIT 4237 vaccinees. We concluded that in young children the RRV-1 (rhesus monkey) rotavirus vaccine is more immunogenic than the RIT 4237 (bovine) rotavirus vaccine, but vaccination with RRV-1 is associated with significant adverse reactions.
A 34-year-old African patient with AIDS developed a new form of oral leucoplakia closely resembling the "hairy" leucoplakia described by Greenspan in male homosexuals in the San Francisco area. A herpes-like virus was seen on ultrastructural analysis with electron microscopy. This case supplies further evidence suggesting that the syndrome in patients originating in Central Africa is similar to the acquired immunodeficiency syndrome (AIDS) reported in American patients.
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A randomised, double-blind, placebo-controlled trial was conducted to evaluate the ability of RIT 4237 live attenuated bovine rotavirus (subgroup 1) vaccine strain to protect against natural rotavirus infection in children. 178 infants aged 8 to 11 months received a single oral dose of RIT 4237 vaccine or placebo and were followed up serologically and clinically during a subgroup 2 rotavirus epidemic. No side-effects attributable to the vaccine were observed. During the 5 months' observation after vaccination 2 of the 86 vaccine recipients and 18 of 92 placebo recipients had rotavirus diarrhoea lasting more than 24 h (p less than 0.001). The vaccine-protection rate was thus 88%. The 2 children in the vaccine group with rotavirus diarrhoea were regarded as primary vaccine failures since they had no detectable serum antibody responses after vaccination. Vaccine prepared from RIT 4237 strain of attenuated bovine rotavirus thus seems to protect children against heterologous subgroup 2 rotavirus diarrhoea.
We have developed a series of monoclonal antibodies against the calf strain RIT 4237 (subgroup 1) and the human strain 82-561 (subgroup 3) of rotavirus, both grown in tissue culture, and also against the human rotavirus 81-2162 (subgroup 2), extracted from a fecal specimen. A variety of different specificities was observed among these antibodies, namely, antibodies against group and subgroup determinants, as well as neutralizing antibodies. By using monoclonal antibodies against the subgroup antigen in an enzyme-linked immunoassay system, the constant predominance of subgroup 2 viruses in humans was confirmed in 74 stools collected from children in Brussels who suffered a diarrheal illness between July 1981 and June 1983. The availability of these antibodies also made it possible to improve the sensitivity and the specificity of the test system.
A candidate oral live rotavirus vaccine, strain RIT 4237, of bovine origin, was tested for immunogenicity and safety in man. In adults the vaccine did not cause clinical symptoms, and a booster response in rotavirus serum antibodies was seen in 2/20 subjects. In seronegative young children one oral dose induced seroconversion to homologous virus in 15/17 (88%) children seronegative by enzyme immunoassay and in 13/19 (68%) children seronegative by a neutralisation assay. The vaccine did not produce gastrointestinal or constitutional symptoms in the children, nor did it cause rotavirus excretion in the stools. The results suggest that the RIT 4237 strain is a promising candidate for a vaccine against human rotavirus, and the vaccine-induced immunity against natural human rotavirus infection should be evaluated in future trials.
The relative prevalence of human rotavirus subgroups was studied during a 3-year period (1978-1981) by means of a sensitive complement fixation technique. Among 93 rotavirus isolates from children with acute gastroenteritis in Brussels, the prevalence of subgroups 1, 2, and 3 was, respectively 24, 17, and 32%. The remaining 27% of strains could not be typed, but no evidence for the existence of any new subgroup was found. The proportion of strains belonging to the different subgroups remained roughly constant during the study period, showing the simultaneous occurrence of the various subgroups of viruses, even during the annual winter peak of rotavirus gastroenteritis.
Studies were performed to evaluate the potential use of the bovine RIT 4237 rotavirus strain as a vaccine candidate against infection with human rotaviruses. Initial experiments revealed that colostrum-deprived piglets were susceptible to infection with several human strains, except for those belonging to subgroup 1. Subsequently, different immunization procedures with RIT 4237 were studied in this animal model. It was found that a two-dose administration, either given intramuscularly (twice) or once intramuscularly and once intragastrically, was necessary to induce a significant serum antibody response. Finally, the protective effect of the latter vaccination schedules against subgroup 2 and 3 rotavirus strains of human origin was evaluated by artificial challenge. In both cases, prior administration of live RIT 4237 significantly decreased fecal shedding of the challenge virus when compared with control animals.
Because of the morbidity and mortality from infection with rotaviruses in children under 2 years, in many parts of the world but especially in developing countries, an urgent need for a vaccine has been recognized. At present, a vaccine candidate of bovine origin, the RIT 4237 strain vaccine developed from a strain received from Mebus et al., is available. This strain has been shown to induce cross protection by challenge of colostrum deprived piglets with human rotavirus strains. Before testing its protective effect in children, preliminary studies in adult volunteers are required to evaluate its degree attenuation and immunogenicity. With regard to the latter we have studied the antibody profile of 87 healthy adults, ages 25 to 40 years, from whom blood samples were taken between January and June 1982. Antibodies versus RIT 4237 were measured both by neutralization and ELISA techniques. Analysis of the results revealed a significant difference in antibody levels according to sex, since high neutralizing antibody titers (greater than 1:320) were observed about 7 times more frequently in women than in men. Furthermore, no seasonal variation in the level and the distribution of serum antibody titers was found when comparing blood specimens taken from male volunteers in winter and spring. As far as antibody levels obtained by neutralization and ELISA assays is concerned, a good correlations was noted in 75% of cases. However, in 22 out of 87 sera high levels of neutralizing antibodies were found in association with low ELISA antibody titers or vice versa. These results suggest that screening of adult volunteers should be performed by means of a neutralization assay prior to administration of a candidate vaccine. However, in the absence of such preliminary testing, male volunteers should be chosen since there is a higher probability of low pre-existing antibody levels among such subjects.
Five enzyme-linked immunosorbent assay systems were adapted for serotyping human rotavirus strains and were compared with a sensitive complement fixation test in terms of specificity and sensitivity. The assays differed mainly with regard to the antibody systems involved in the double sandwich. Serotype differentiation of 34 rotavirus strains was achieved by determining a neutralization endpoint titer, either with a constant antiserum-varying antigen dilution method or vice versa. The procedure which proved to be highly specific and sensitive was one with two type-specific hyperimmune sera (enzyme-linked immunosorbent assay system 5) instead of only one, as in the four other systems.
A healthy 26-year-old patient presented a primary herpetic type 2 infection. The infection disseminated to the skin, the mucosa and the liver. The clinical course of the infection had a favorable issue.
To determine the relative importance of two known serotypes of human rotavirus, we developed an enzyme-linked immunosorbent assay to differentiate serotype-specific rotavirus antigen and antibody. Using this technic, we studied the epidemiology of the two serotypes in acute gastroenteritis. Seventy-seven per cent of 414 rotavirus isolates were Type 2, and the remainder were Type 1. The serotype distribution was similar in specimens from children in Washington, D.C., and other parts of the world. Sero-epidemiologic studies revealed that most children living in the Washington, D.C., area acquired antibody to both types by the age of two years. An analysis of children who were reinfected indicated that sequential infections usually involved different serotypes and that illness caused by one serotype did not provide resistance to illness caused by the other serotype. These results suggest that, to be completely effective, a vaccine must provide resistance to both serotypes.
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Explore the source record for details and available documents.
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Explore the source record for details and available documents.