Key result
Oral inoculation with Rotashield caused hepatitis and/or bile-duct obstruction in 62% of infant CB17(scid) mice at 6 days, compared to 0% with WC3-PV or placebo (P<0.005).
Rotashield, but not WC3-PV, induces hepatitis and bile-duct obstruction in infant CB17(scid) mice, indicating different biological activities.
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Warrants caution interpreting rotavirus vaccine strain differences; leaves open human translation from immunodeficient mouse models.
The effects of oral inoculation into infant CB17(scid) mice of two reassortant rotavirus vaccines were compared. The vaccines were Rotashield and WC3-PV, a mixture of five reassortants (G1, G2, G3, G4 and P1; pentavalent reassortant vaccine). Control mice were inoculated with a placebo. At 6 days post-inoculation (p.i.), 8 of 13 (62 %; P<0.005) Rotashield-inoculated mice developed hepatitis and/or bile-duct obstruction compared with none of 11 mice given WC3-PV and none of 14 given placebo. In the Rotashield-inoculated mice, only serotype G3 rhesus rotavirus (RRV) was isolated from multiple sites, including intestine, liver, pancreas, spleen, blood and mesenteric lymph nodes. Recovery of RRV from Rotashield-inoculated mice followed a biphasic pattern. The two peaks of RRV recovery appeared to coincide firstly with replication in the intestine during days 1-3 p.i., and secondly with virus infection of the liver from days 10 to 15 p.i. WC3 reassortants of four different serotypes were detected only at day 1 p.i. in the intestine, liver, pancreas and blood cells from three WC3-PV-inoculated mouse pups. However, WC3-PV did not produce any hepatopathology. Rotashield and WC3-PV appeared to exhibit different biological activity in infant CB17(scid) mouse pups.
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Qiao et al. (2004) studied Rotavirus vaccination (n=38). Rotashield vs. WC3-PV and placebo was evaluated on Hepatitis and/or bile-duct obstruction at 6 days post-inoculation (p=<0.005). Oral inoculation with Rotashield caused hepatitis and/or bile-duct obstruction in 62% of infant CB17(scid) mice at 6 days, compared to 0% with WC3-PV or placebo (P<0.005).
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