Prevalence of neutralizing antibodies against a candidate rotavirus vaccine in adults.

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.

Monoclonal antibodies directed against different antigenic determinants of rotavirus.

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.

Prevalence of subgroup 1, 2, and 3 rotaviruses in Belgian children suffering from acute diarrhea (1978-1981).

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.

Protection studies in colostrum-deprived piglets of a bovine rotavirus vaccine candidate using human rotavirus strains for challenge.

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.

Characterization and description of "Campylobacter upsaliensis" isolated from human feces.

During a 3-year period, "Campylobacter upsaliensis" was isolated from 99 patients. Phenotypic characterization and numerical analysis of protein electrophoregrams showed evidence that "C. upsaliensis" is a distinct Campylobacter species with unique characteristics. The MBCs of 13 antibiotics were determined. In general, these organisms were highly susceptible to drugs that were present in the selective isolation media, making none of the available selective media suitable for the isolation of "C. upsaliensis." Ten strains were found to be resistant to erythromycin (MBCs, greater than or equal to 12.50 mg/liter). Plasmid DNA was detectable in 89 of the 99 strains; 16 plasmid profiles could be identified. Plasmid pattern 16, containing four plasmids of 52, 32, 5.5, and 2.6 megadaltons, represented 60.7% of the plasmid-containing strains. None of the "C. upsaliensis" strains could be agglutinated with antisera against heat-labile antigens from C. jejuni, C. coli, or C. laridis. "C. upsaliensis" was found to be susceptible to serum killing and was readily phagocytized by human polymorphonuclear cells.