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Haemophilus influenzae type b Antibody

Haemophilius influenzae is a species of bacteria that has encapsulated or unencapsulated strains. Encapsulated strains express one of six antigenically distinct capsular polysaccharides that are named types a, b, c, d, e, or f. H. influenzae colonizes the upper respiratory tract of humans and is transmitted from person to person by inhalation of respiratory droplets or by direct contact with respiratory tract secretions.

Before 1985, Haemophilus influenzae type b (Hib) was the leading cause of bacterial meningitis. It also caused other invasive diseases in children aged <5 years including epiglottitis, pneumonia, septic arthritis, cellulitis, pericarditis, and bacteremia. Fifteen to 30 percent of survivors had permanent hearing impairment or severe neurologic sequelae. Approximately 4% of cases were fatal.

Hib disease is uncommon in adults and in children aged >5 years. Persons who are immunocompromized are considered at increased risk for invasive Hib disease including:

  • functional or anatomic asplenia
  • HIV infection
  • immunoglobulin deficiency including immunoglobulin G2 subclass deficiency
  • early component complement deficiency
  • hematopoietic stem cell transplant
  • chemotherapy or radiation therapy for malignancy

Encapsulated H. influenzae strains, other than type b, can cause invasive disease similar to Hib disease. Nonencapsulated strains are not typeable. Nontypeable strains most commonly cause mucosal infections such as otitis media, conjunctivitis, and sinusitis, but can cause invasive disease.

The first monovalent Hib vaccine was introduced in the United States in 1985. It consisted of purified polyribosylribitol phosphate polysaccharide. This vaccine was ineffective in children aged <18 months because of the T lymphocyte-independent nature of the immune response to the polysaccharide. Conjugate Hib vaccines were introduced in 1987 and 1989. Conjugation of the PRP polysaccharide with protein carriers bearing T-lymphocyte epitopes enhanced immunologic response to the PRP antigen and increased immunologic memory.

Three monovalent PRP polysaccharide-protein conjugate vaccines have been licensed by the FDA including PRP-OMP (PedvaxHIB, Merck), PRP-T (ActHIB, Sanofi Pasteur), and PRP-T (Hiberix, GlaxoSmithKline). FDA has also licensed 3 combination vaccines including PRP-OMP/HepB (Comvax, Merck), DTaP-IPV/PRP-T (Pentacel, Sanofi Pasteur), and MenCY/PRP-T (MenHibRix, GlaxoSmithKline). No vaccines are available to prevent disease by nontype b or nontypeable Haemophilus influenzae strains.

ACIP recommends routine administration of Hib vaccine series beginning at age 2 months. Infants aged 2–6 months should receive a 3-dose series of Hib PRP-T as ActHib, Pentacel, or MenHibRix or a 2-dose series of Hib PRP-OMP as PedvaxHib or Comvax. A booster dose of any licensed conjugate Hib vaccine or Hib vaccine in combination with HepB or DTaP/IPV is recommended at age 12 through 15 months.

Long-term protection from invasive Hib disease is correlated with serum anti-PRP levels ?0.15 µg/ml in unvaccinated children and ?1.0 µg/ml in vaccinated children. Protective antibody levels are detected for both PedvaxHib and ActHib after a primary series. However, the vaccines differ in the timing of antibody response. PedvaxHib produces a substantial antibody response after the first dose with an additional boost in antibody concentration after the second or third dose. Geometric mean antibody concentrations remain at or below 1.0 µg/ml after the first and second dose of ActHIB, but a protective antibody response is seen after the third dose.

Antibody levels decline after completion of the primary series with PRP-T and PRP-OMP, vaccines, so a booster dose at age 12–15 months is necessary to maintain protective antibody levels. Booster doses of PedvaxHib, ActHib, and Hiberix at age 12–15 months provide levels of antibody that are protective against invasive Hib disease

Hib vaccination has decreased the annual incidence of invasive Hib disease in children aged <5 years decreased by 99%, to less than one case per 100,000 children. Hib vaccines only protect against H. influenzae type b strains. Today, the majority of Hib disease in the United States occurs among unimmunized and underimmunized infants and children who have not completed the primary series or failed to get a booster dose.

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