Trial Information

Descriptive Immunogenicity of 2 Doses of Pneumococcal 7-valent Conjugate Vaccine (Prevenar®, Wyeth Lederle) Followed by Pneumococcal Polysaccharide Vaccine (Pneumovax® Aventis Pasteur MSD) in Ataxia-telangiectasia Patients

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.