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:

• Healthy infants 6, 9, or 12 months (+ 3 weeks) of age
• Free of obvious health problems as established by medical history and clinical examination before entering into the study
• Parent/legal guardian willing and capable of signing written informed consent
• Parent/legal guardian expected to be available for entire study
• 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:

• Former premature infants (<36 weeks)
• Birth weight < 2500grams
• Significant underlying chronic illness
• Immunodeficiency disease or immunosuppressive therapy in the participant
• Any other condition which in the clinical judgment of the investigator might interfere with vaccine evaluation
• Allergy to any components of the vaccine, including anaphylaxis or anyphalaxoid reaction to neomycin or eggs
• Administration of an investigational drug
• Blood products within 3 months of initial enrollment
• Current febrile respiratory illness or other active febrile infection
• Family history of congenital/hereditary immunodeficiency, unless immune competence of subject has been determined.
• Blood dyscrasias, leukemia, lymphomas of any type or other malignant neoplasms affecting the bone marrow or lymphatic systems.