Live attenuated influenza vaccines in young seronegative children

Abstract

Seronegative children undergoing primary infection sensitively reflect the residual virulence of an experimental attenuated respiratory vitral vaccine. Two temperature sensitive (ts) A/Hong Kong influenza vaccines derived following chemical mutagenesis of a cloned stock of A/Great Lakes/65 have been evaluated in vaccine trials in seronegative children. The two vaccines, ts-1[A] and ts 1[E], differ in their laboratory characteristics. Ts-1[A] has a lower shut-off temperature, 37 degrees C vs 38 degrees C, and more limited replication in the Syrian hamster model system than ts-1[E]. In A/HK seronegative adults ts-1[A] is noninfectious whereas ts-1[E] will replicate and induce an antibody response. The genetic lesion of ts-1[A] was stable in the young child; in contrast, late in the course of virus shedding, ts-1[E] exhibited genetic instability with 4 individuals shedding virus which had lost the ts marker. Transmission to controls was rare with both vaccines being observed in only 1 of 5 controls with ts-1[A] and none of six controls with ts-1[E]. There were no respiratory symptoms associated with ts-1[A] vaccine virus shedding. Ts-1[E] virus shedding had a suggestive association with fever and cough in the seronegative child. The trials in seronegative children extent and confirm the inherent differences between ts-1[A] and ts-1[E] vaccine strains and support the concept that laboratory markers of attenuation are predictive of vaccine behavior in the seronegative child.