Multivalent huma-bovine retavirus vaccine
A technology of bovine rotavirus and rotavirus, applied in the field of multivalent human-bovine rotavirus vaccine
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Embodiment I
[0038] This example describes rotaviruses derived from human rotavirus strains D (VP7:1), DS-1 (VP7:2), P (VP7:3) and ST (VP7:4) and bovine UK Compton (UK) rotaviruses. The rotavirus rearrangements were prepared, and the safety, immunogenicity and reactogenicity of each rearrangement were evaluated for adults, children and infants.
[0039] From bovine UK Compton (UK) strains and from human rotavirus strains D (VP7 serotype 1, ATCC VR-970), DS-1 (VP7 serotype 2; Wyatt et al., Perspect. Virol. 10:121-145 (1978)) and P (VP7 serotype 3, Wyatt et al., Science 207:189-171 (1983)) and ST3 (VP7 serotype 4; Banatvala et al., Journal of the American Veterinary Medical Association (J.Am. Vet. Med. Assoc.) 173:527-530 (1978)) derived human X bovine rearranged rotavirus strains representing VP7 serotypes 1, 2, 3 and 4. Human rotavirus strains D, DS-1 and P were recovered from the stool of children hospitalized with diarrhea; strains D and DS-1 were propagated and passaged in sterile calv...
Embodiment II
[0074] This example describes a tetravalent human x bovine rearranged rotavirus immunogenic composition evaluated for its clinical safety and immunogenicity in adults, children and infants.
[0075] The four human x bovine rearranged rotaviruses described in Example 1 were mixed in equal volumes to form a single tetravalent vaccine composition. All studies were performed in a placebo-controlled fashion to evaluate the safety and immunogenicity of the mixed compositions. All serotyping and microbiological determinations were performed as described in Example 1.
[0076] A single dose of undiluted 10 5.3 -10 5.8PFU per rearranged quadrivalent human (VP7 serotypes 1, 2, 3 and 4)-bovine UK rotavirus vaccine. Study subjects fasted for at least 1 hour before or after administration of the vaccine or placebo. They were given 120 ml of a buffer (sodium bicarbonate) to neutralize stomach acid, followed one minute later by either the tetravalent immunogenic composition mixed with th...
Embodiment III
[0092] This example provides data from an ongoing clinical trial comparing the preferred tetravalent human-bovine rearranged rotavirus composition of the invention with the approved tetravalent macaque-human rotavirus rearranged vaccine ROTASHIELD. Summary of preliminary phase analysis. This assay examined the proportion of low-level febrile responses and protective efficacy against rotavirus diarrhea for both compositions.
[0093] A phased two-year clinical study is currently underway to compare the quadrivalent human-bovine rearranged rotavirus composition of the present invention with the quadrivalent macaque-human rotavirus rearranged vaccine (recently approved in 15 countries in the United States and the European Community) Safety and efficacy of anti-rotavirus diarrhea using ROTASHIELD). The study was conducted in Finland and included 172 quadrivalent human-bovine rotavirus rearrangement subjects, 86 corresponding placebo controls, 161 ROTASHIELD vaccinators and 79 cor...
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