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Impaired polysaccharide responses in immunodeficient patients: relevance to bone marrow transplant patients
1Dana-Farber Cancer Institute, Boston, MA 02115.
Insights
Bone marrow transplant patients face higher risks of bacterial infections. New conjugate vaccines show promise for improving immune responses in these patients and other immunodeficient groups.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Bone marrow transplant (BMT) patients are susceptible to encapsulated bacteria like Streptococcus pneumoniae and Haemophilus influenzae type b (Hib).
- Age-related susceptibility in children and immune reconstitution post-BMT share similarities, including poor polysaccharide response and low IgG2 levels.
- Specific immunodeficient groups, including IgG2 subclass deficiency and selective antibody deficiencies, also exhibit increased risk for these infections.
Purpose of the Study:
- To evaluate the response of bone marrow transplant patients to a Hib conjugate vaccine.
- To understand the immunological similarities between immune reconstitution in BMT patients and healthy children's immune development.
- To assess the efficacy of Hib conjugate vaccines in various immunodeficient populations.
Main Methods:
- The study focuses on identifying patient groups at risk for encapsulated bacterial infections.
- Analysis of serum IgG2 and IgG4 subclass concentrations in relation to infection risk and vaccine response.
- Evaluation of the immunogenicity of new Hib polysaccharide conjugate vaccines in healthy children and immunodeficient groups.
Main Results:
- Hib conjugate vaccines are more immunogenic in healthy children than traditional polysaccharide vaccines.
- These conjugate vaccines elicit protective responses in identified immunodeficient groups, including those with Hib vaccine failures and specific ethnic groups with higher infection rates.
- Immune reconstitution post-BMT is characterized by a slow return of polysaccharide response and IgG2 concentrations, mirroring immune maturation.
Conclusions:
- Hib conjugate vaccines offer a promising strategy for preventing infections in bone marrow transplant patients.
- The findings support the use of conjugate vaccines for broader populations with specific antibody deficiencies.
- Understanding immune reconstitution post-BMT is crucial for optimizing vaccination strategies in these vulnerable patients.
Abstract:
Bone marrow transplant patients are at increased risk for pneumococcal and H. influenzae type b (HIB) infections. These polysaccharide encapsulated bacteria are also pathogens for young healthy children. In healthy children age related susceptibility has been associated with poor response to polysaccharides and low serum IgG2 subclass antibody concentrations. Of note, immune reconstitution following bone marrow transplantation has been characterized by slow return of both the response to polysaccharides and IgG2 serum concentrations. Thus immune reconstitution following bone marrow transplantation is similar to the maturation that occurs in healthy children. In addition to transplant patients, we have identified five groups of immunodeficient patients who are at increased risk for polysaccharide encapsulated pathogens. IgG2 subclass deficient patients were shown to have impaired responses to polysaccharide antigens. We have also defined "Selective Antibody Deficiencies" which are individuals with normal IgG subclass concentrations but poor responses to polysaccharide antigens. Next, patients who developed HIB disease in spite of immunization (i.e. HIB vaccine failures) were demonstrated to have lower serum IgG2 and IgG4 subclass concentrations compared to controls. Finally, Native Americans (an ethnic group with an increased incidence of pneumococcal and HIB infections) were shown to be poor responders to polysaccharide antigens and have significantly lower concentrations of serum IgG2 and IgG4 as compared to controls. New HIB polysaccharide vaccines linked to protein antigens (conjugate vaccines) have been developed that are more immunogenic in healthy young children. In addition, these conjugate vaccines have resulted in protective responses in each of the newly described immunodeficient groups. We therefore now propose to evaluate bone marrow transplant patients' response to HIB conjugate vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)