SUSCEPTIBILITY TO INVASIVE H. INFLUENZAE (Hi) INFECTION IMMEDIATELY AFTER IMMUNIZATION WITH THE CAPSULAR VACCINE

Abstract

To understand the immunologic mechanism underlying early (<7 day) “vaccine failure” after administration of the Hi capsular polysaccharide vaccine (HiPV), we used the infant rat model to evaluate whether HiPV might, for a short period, decrease the protection afforded by anticapsular antibody (ACA). 74 five day old infant rats were passively protected with bacterial polysaccharide immune globulin (BPIG) prepared from adults immunized with HiPV. One day later, the mean ACA concentration was 173 ± 85 ng/ml. The pups were immunized 24 hours after BPIG with either 75 or 7500 ng HiPV. The lower HiPV dose was extrapolated from that currently recommended for infants. Controls were given BPIG alone or HiPV alone. All animals were challenged ip with 5×103 cfu Hi type b one day after immunization. Detectable bacteremia and meningitis were more frequent in HiPV immunized BPIG recipients than in unimmunized BPIG recipients (100* vs 18%, p<.00001 for bacteremia and 100% vs 18%, p<.00001 for meningitis). Also, in bacteremic animals, the magnitude of bacteremia in the BPIG/HiPV recipients exceeded that in BPIG protected, non-HiPV recipients (104.6 vs 102.1, p=.0005). HiPV administration did not deplete complement. However, animals given BPIG followed by HiPV had lower mean ACA concentrations than animals receiving BPIG alone (29 vs 151 ng/ml, p < .01). Moreover, ACA was undetectable (< 25 ng/ml) in 18/20 BPIG/HiPV recipients. We conclude that immunization with HiPV may decrease the ACA concentration and produce a ‘window’ of susceptibility to Hi disease in the early post-vaccination period.