Antibody Production in Immune Disorders

The purpose of this study is to evaluate immune responses to vaccines in subjects (both
children and adults) with known or suspected primary immune disorders. We intend to
characterize immune responsiveness to standard, well characterized antigens (vaccines) in
subjects with primary immune disorders, and/or in subjects who have received treatments to
correct their primary immune disorders. This will be an open label, prospective study
investigating the functional status of the adaptive immune system. Up to 50 subjects may be
enrolled. It is anticipated that subjects will be referred by any investigators at NIH
studying inherited disorders of the immune system under their own protocols.

After giving standard vaccines, we will test specific antibody. The vaccines include licensed
and universally mandated diphtheria and tetanus toxoid, two licensed pneumococcal vaccine
formulations recommended for protection of children from pneumonia, and rabies vaccine
licensed in 1997 (not the formerly available reaction-prone formulation). We will obtain
peripheral blood samples from subjects before vaccination and at a specific time intervals
after vaccination. Measurement of specific antibody titers will be conducted by the
immunology laboratory at the Department of Laboratory Medicin at the NIH. Subjects may be
offered one or more of the vaccines based on available information about their exposure
history and their immune status, and the vaccines may be offered sequentially or in
combination to shorten study time.

While the vaccines used here are often medically indicated and given outside of research
protocols both to provide protection and to assess immune responses, the investigators have
elected to use a protocol for the following reasons:

- Enhancement of subject understanding of the use of vaccines for in vivo assessment of
immune responses.

- Emphasis on the importance of obtaining pre- and post-immunization blood samples to
monitor how well the body's immune system is working.

- Administration of rabies vaccine to subjects who would not ordinarily need it.

- Recognition that vaccine side effects have been widely publicized and may be of concern
to potential enrollees.

- INCLUSION CRITERIA:

Individuals being evaluated by NIH investigators for known or suspected primary immune
disorders.

Women of childbearing potential and men must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) for at least 21 days prior to receipt of
each vaccine and for the duration of study participation.

EXCLUSION CRITERIA:

Documented HIV infection.

Active malignancy.

Immunosuppressive therapy, other than steroids.

Symptomatic cardiac disease or ongoing treatment for it.

Pregnant or lactating women (due to restrictions on use of vaccines).

Surgery during the two weeks prior to entry.

Serious, ongoing, or uncontrolled infections.

Platelet count less than 40,000/microL or other coagulation disorder.

Any other major illness that, in the investigator's judgment, may substantially increase
the risk associated with the patient's participation in this study.

History of previous systemic reaction to the particular vaccine product being considered
for administration.

For RabAvert, persons known to be sensitive to:

- Processed bovine gelatin

- Chicken protein

- Neomycin

- Chlortetrycyline

- Amphotericin B

For Prevnar, persons with know or possible latex sensitivity.