Ontogeny of Measles Immunity in Infants

This is an open-label immunogenicity and safety study of live attenuated Measles Vaccine
(Attenuvax) and Measles-Mumps-Rubella (MMR-II) vaccine administered to healthy children at 6
(n=70), 9 (n=70), or 12 (n=70) months of age. Attenuvax (Measles Virus Vaccine Live, Merck &
Co., Inc) and MMR-II (Measles-Mumps-Rubella Virus Vaccine Live, Merck & Co., Inc) will be
delivered as 0.5 mL per dose, administered subcutaneously. Both vaccines are licensed for
use in infants in the United States. MMR-II is recommended as part of the childhood
immunization schedule by the AAP and ACIP, and Attenuvax is recommended for use as a single
component vaccine in infants 6-11 months particularly for foreign travel and in measles
outbreaks79. Infants vaccinated with Attenuvax at 6 or 9 months receive MMR-II at 12 months
of age as recommended for follow-up vaccination. Immunization against measles is given as a
trivalent formulation with mumps and rubella and is indicated as a primary dose at 12-15
months of age with a second dose recommended routinely at time of school entry, 4-6 years of
age, but can be given at any earlier age provided that the interval between the first and
second doses is at least 4 weeks .

Two hundred and ten healthy children attending the Palo Alto Medical Clinic will be
recruited into one of three cohorts over a five year period. (Table 1). All children in
cohort 1 and 2 (6 and 9 month old infants) will receive Attenuvax as part of their
participation in this study followed by MMR-II at 12 months of age as part of their routine
WCC and not as a study vaccine. Infants recruited into cohort 3, (twelve month old infants)
will receive one dose of MMR-II at 12 months. All infants in the study (cohort 1, 2 or 3)
are receiving MMR-II at 12 months as part of their routine childhood vaccines. The
vaccination schedules is summarized in Table 1. Other immunizations as required for routine
WCC will be administered simultaneously. Participation will entail 2-4 visits, 2-3 blood
samples, and 1-2 immunizations and will end after the 9-18 month visit, totaling 3 to 12
months time of participation for a subject depending on cohort and if participants opt for a
second follow-up blood sample.

Inclusion Criteria:Subjects must meet all of the following criteria in order to be
enrolled:

1. Healthy infants 6, 9, or 12 months (+ 3 weeks) of age

2. Free of obvious health problems as established by medical history and clinical
examination before entering into the study

3. Parent/legal guardian willing and capable of signing written informed consent

4. Parent/legal guardian expected to be available for entire study

5. Parent/legal guardian can be reached by telephone

Exclusion Criteria:All subjects meeting any of the following exclusion criteria at
baseline will be excluded from study participation:

1. Former premature infants (<36 weeks)

2. Birth weight < 2500grams

3. Significant underlying chronic illness

4. Immunodeficiency disease or immunosuppressive therapy in the participant

5. Any other condition which in the clinical judgment of the investigator might
interfere with vaccine evaluation

6. Allergy to any components of the vaccine, including anaphylaxis or anyphalaxoid
reaction to neomycin or eggs

7. Administration of an investigational drug

8. Blood products within 3 months of initial enrollment

9. Current febrile respiratory illness or other active febrile infection

10. Family history of congenital/hereditary immunodeficiency, unless immune competence of
subject has been determined.

11. Blood dyscrasias, leukemia, lymphomas of any type or other malignant neoplasms
affecting the bone marrow or lymphatic systems.