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Hemophilus influenzae type B disease in children vaccinated with type B polysaccharide vaccine
Insights
Vaccine failure in Hemophilus influenzae type b disease may stem from genetic factors, leading to deficient antibody responses to the polysaccharide vaccine despite normal immunoglobulin levels.
Area of Science:
- Immunology
- Pediatrics
- Vaccinology
Background:
- Invasive Hemophilus influenzae type b (Hib) disease poses a significant threat to children.
- Hib polysaccharide vaccines are crucial for prevention, but vaccine failure can occur.
Purpose of the Study:
- To investigate host factors contributing to Hib polysaccharide vaccine failure in children.
- To compare antibody responses in vaccinated children with Hib disease versus unvaccinated children with Hib disease.
Main Methods:
- Studied 55 children with invasive Hib disease occurring after vaccination.
- Measured antibody concentrations to Hib polysaccharide, immunoglobulin levels (IgG2), and antibody responses to tetanus toxoid.
- Assessed Gm immunoglobulin phenotype and hemolytic complement activity.
Main Results:
- Vaccinated children with Hib disease had significantly lower antibody concentrations to Hib polysaccharide compared to unvaccinated children.
- Most vaccine failures were not associated with hypogammaglobulinemia or low IgG2 levels.
- The Gm immunoglobulin phenotype (1,2,3, 17; ;5,13,21) was linked to a sevenfold increased risk of vaccine failure in white children.
Conclusions:
- Hib vaccine failure may be partly due to genetic factors influencing antibody response.
- Many vaccinated children experiencing Hib disease exhibit inadequate antibody responses to the polysaccharide antigen.
- Normal immunoglobulin and tetanus toxoid antibody levels do not preclude vaccine failure.
Abstract:
We studied 55 cases of invasive Hemophilus influenzae type b disease occurring in children at least three weeks after vaccination with type b polysaccharide vaccine. Their mean age at the time of immunization was 27.8 months (range, 18 to 47). Meningitis developed in 39 patients, of whom 3 died and 6 had neurologic sequelae. We investigated certain host factors that may have contributed to the failure of the vaccine. The geometric mean concentration of antibody to type b polysaccharide in convalescent-phase serum from 31 of the vaccinated patients who had hemophilus disease was significantly lower than that in serum from 25 patients of similar age with the disease who had never been vaccinated (0.59 vs. 3.46 micrograms per milliliter, P less than 0.001). However, only 3 of 46 patients in whom the vaccine failed and who were tested for hypogammaglobulinemia had this finding, and none of 33 children tested for IgG2 had low serum concentrations of this immunoglobulin subclass, which is thought to be important in the immune response to polysaccharide antigens. In addition, all but 1 of the 46 patients in whom the vaccine failed and who were tested for IgG antibody to tetanus toxoid protein, a thymic-dependent antigen, had normal values, and 19 of 20 tested for hemolytic complement activity had normal levels. In white children, the presence of the Gm immunoglobulin phenotype (1,2,3, 17; ;5,13,21) was associated with a sevenfold increase in the relative risk of vaccine failure (P less than 0.003). We conclude that vaccine failure may be related in part to genetic factors, and that most vaccinated children in whom Hemophilus influenzae disease develops have deficient antibody responses to the type b polysaccharide despite normal serum concentrations of immunoglobulin and normal antibody responses to tetanus toxoid.