DEVELOPMENT OF RECOMBINANT BCG-VP8 VACCINES

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Rotavizuses are the major cause of severe diarrhea in infants and young children in both developed and developing countries. Two outer capsid rotavirus proteins, VP7 and VP4, are associated with the induction of neutralizing antibodies which have been shown in experimental animals to be associated with resistance to illness. Serotype specificity is associated primarily with VP7. However, recent studies have elucidated the antigenic relationships of the VP4 of human rotaviruses which appear to be less polymorphic than VP7. Human rotavirus strains that are associated with symptomatic infection and that exhibit VP7 specificity of serotype 1, 2, 3, 4 or 9 each possess a similar VP4 as determined by neutralization assay. Objectives of this study were: (i) to use the VP8 subunit of VP4 to develop a BCG-VP8 recombinant and evaluate its ability to induce specific rotavirus neutralizing antibodies in experimental animals, and (ii) to utilize the information thus obtained for the development of a human rotavirus vaccine for oral administration. The cDNA representing the VP8 subunit of outer capsid rotavirus protein VP4 from the human rotavirus KU strain was cloned in three different BCG vectors. The VP8 subunit expressed in these systems was recognized in an immunoblot assay by antibodies present in hyperimmune antiserum to: (i) human rotavirus strain Wa, (ii) expressed KU-VP4, and (iii) expressed KU-VP8, a cleavage subunit of VP4. These observations suggest that the VP8 subunit was expressed in an antigenically correct form by the recombinant as authentic VP8.