Immunogenicity of Pneumococcal Vaccines in Ataxia-telangiectasia Patients

• Primary end point will be levels of antibodies against 13 serotypes of streptococcus pneumoniae following vaccination with 2 doses of PCV7 and 1 dose of PPV23. All endpoints will include both ELISA and OPA antibodies. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  

Biological: Prevenar® (7-valent pneumococcal conjugate vaccine)

Pneumococcal vaccines (conjugate and polysaccharide)

Intramuscular Injections: 2 doses of 7-valent pneumococcal conjugate vaccine 8 weeks apart and 1 dose of pneumococcal polysaccharide vaccine 8 weeks later

Other Names:
• Prevenar®, Wyeth
• Pneumovax® Aventis Pasteur MSD
Biological: Pneumovax® (pneumococcal polysaccharide vaccine)

Pneumococcal vaccines (conjugate and polysaccharide)

Intramuscular Injections: 2 doses of 7-valent pneumococcal conjugate vaccine 8 weeks apart and 1 dose of pneumococcal polysaccharide vaccine 8 weeks later

Ataxia-telangiectasia (AT) is a rare progressive neurodegenerative autosomal recessive disorder characterized by cerebellar ataxia, neuromotor dysfunction, oculocutaneous telangiectasia and immunodeficiency. AT patients are vulnerable to cancer and infection and usually die during their 2nd or 3rd decade due to these complications. Life expectancy does not correlate well with severity of neurological impairment. The main cause of death is respiratory infections because these patients are known to have severe type of immunodeficiency. The immunodeficiency of AT patient consists of both humoral defect (immunoglobulin deficiency and reduced response to polysaccharide antigens) and cell-mediated defect (reduced lymphocytes number and function). Consequently, pneumonia is the most common infection seen in AT patients, and is usually caused by S. pneumoniae. Therefore, a routine schedule of pneumococcal vaccine is highly recommended in AT cases where immunoglobulin replacement therapy was not already initiated.

Until recently, AT patients were immunized with the pneumococcal polysaccharide vaccine (PPV23, Pneumovax® Aventis Pasteur MSD). However, data have shown that they do not respond well to these vaccine mainly because of their reduced response to polysaccharide stimulation. Recently, the Israeli Ministry of Health has approved the pneumococcal 7-valent conjugate vaccine (PCV7, Prevenar®, Wyeth Lederle) for AT patients of all ages. In contrast to polysaccharide vaccines, this conjugate vaccine is known to stimulate the immune system through T-cell dependent mechanism, and therefore the response is expected to be higher. The approved Israeli schedule for immunization of AT patients includes children older than 2 years that are entitled to receive 2 doses of PCV7 (8 weeks apart) boosted by PPV23, eight weeks after the second dose of PCV7. Assessment of the immunogenicity of such pneumococcal vaccination protocol in AT patients has never been performed.

The "Safra" Children's Hospital is the national multi-disciplinary center caring for AT patients. Approximately 50 patients from all over the country (including Jewish, Druze, Bedouin and other Muslim patients - 3 of whom are Palestinians) are followed in the clinic on a monthly basis.

Approximately 20 AT patients are not receiving IVIG replacement therapy, therefore are entitled to receive pneumococcal vaccination as stated above (mean age 10.6, 3 -23 years, 3 less than 5 years.

The aim of this study is to evaluate the responsiveness, determined by specific antibody production, of AT patients receiving the new vaccine protocol that was recently approved to use by the Israeli Ministry of Health.