Haemophilus influenzae type b (Hib)
Haemophilus influenzae is a Gram-negative coccobacillus that commonly infects the upper respiratory track of children through the transfer of nasal secretions. Whereas non-encapsulated strains of the bacillus are relatively benign, strains with a polysaccharide capsule or coat cause a more serious disease. The polysaccharide, is the primary factor associated with virulence. Of the 6 capsular types of H influenzae, type b (Hib) is responsible for more than 90% of systemic infections. This organism causes primarily pneumonia and meningitis in young children and it is a significant public health concern in many parts of the world, with as many as 3 million cases of serious disease occurring every year. The increasing resistance of Hib to antibiotic agents has been reported from many parts of the world, and vaccination is the only public health tool that can rapidly reduce the incidence of Hib disease globally.
Conjugate Hib vaccines are liquid or lyophilized preparations of the purified polyribosylribitol phosphate (PRP) capsular polysaccharidge of Hib, which is chemically linked to a carrier protein. The Hib vaccines currently available for immunizing infants are based on purified or synthetic PRP conjugated either to the non-toxic mutant diphtheria toxin CRM 197, tetanus toxoid, or the meningococcal outer membrane protein. Hib vaccine is available commercially as a monovalent preparation, as well as in combination vaccines containing DTP, sometimes along with hepatitis B and/or or IPV. A PRP antibody concentration of >0.15 µg/ml is considered to be a serological marker for short-term protection; concentrations ≥1.0 µg/ml 1 month after the completion of primary immunization are considered to be markers of long-term protective immunity against invasive Hib disease.
Hib Vaccine Standardization
The WHO recommendations for the production and quality control of Hib conjugate vaccines were adopted by the Expert Committee on Biological Standardization in 1990 were modified in 1998 due to the poor correlation found between the biological assay of potency and clinical efficacy in infants. Animal tests were replaced by physio-chemical tests of potency for the purpose of batch (lot) release at this time.
Recommendations for the production & control of Haemophilus influenzae type b conjugate vaccines, TRS No. 897, 2000
A WHO reference material for the polysaccharide capsule protein for Hib vaccine is available to qualified applicants: