Spontaneous capsule loss in Haemophilus influenzae serotype b associated with Hib conjugate vaccine failure and invasive disease

Abstract: The incidence of invasive Hib disease has fallen dramatically due to the enormous success of the H.influenzae serotype b (Hib) vaccine. Hib vaccine failures, though rare, do occur with many being unexplained. We present here a case of invasive Haemophilus disease in a partially vaccinated child where the isolated Hib strain consistently underwent spontaneous capsule loss producing capsule deficient mutants (Hibminus) at a rate of 1-2%. Whole genome sequencing confirmed that both Hib and Hib-minus strains were almost identical. The Hib-minus strain was notably lacking the complete bexA capsule transport gene. The patient had no predisposing risk factors for infection suggesting that capsule loss may have contributed to the vaccine failure and infectious disease. The present case highlights the necessity for thorough molecular investigation of unexplained Hib vaccine failures.