The objective of this project is to evaluate the immune response to measles vaccine administered by aerosol to children.
The specific aims are: 1) To evaluate measles vaccine by aerosol and subcutaneous route in children of 12, 9 and 6 months old. 2) To evaluate the effect of passive antibodies on the capacity of the aerosol measles vaccine to elicit a humeral and cellular response. 3) To evaluate the secretary IgA response to measles vaccine given by aerosol and subcutaneous route in children 12, 9 and 6 months old. 4) To evaluate the response to subcutaneous revaccination in children who were given aerosol for their first dose. 5) To compare the cellular responses of infants to bacterial and viral antigens according to the route of measles vaccine administration. Measles is still a problem of public health. Despite the availability of live measles vaccine, measles infections account for 10% of global mortality of all causes among children less than 5 years old. Measles is highly transmissible and outbreaks can still emerge. The aerosol measles vaccine could be helpful in mass vaccination, because it is easy to deliver and is well accepted by children and mothers. The Pan American Health Organization has targeted the year 2010 for measles eradication in the Americas. In addition to the potential benefits for immunogenicity, the mucosal delivery of measles vaccine may have practical advantages for measles eradication programs. This study is based on a very well established partnership between the National Autonomous University of Mexico, National Institute of Public Health of Mexico and Stanford University. We plan to enroll 630 children during a 5-year period. Children will be identified from birth records for Queretaro, Queretaro, Mexico. The eligibility criteria will be healthy children of 6, 9 and 12 months old. They will be randomized in a 1:1 ratio to receive measles vaccine by aerosol or subcutaneous route. Blood draws will be taken before vaccination and 12 weeks after immunization for Specific Aim 1 and 2.
For Specific Aim 4 a subgroup of children (of each age cohort and each vaccine) will have a third blood draw 3 months after a booster with MMR at 12 or 15 months old (6 and 9 month old children will receive a booster at 12 months of age, and 12 month-old children will receive a booster at 15 months of age).
For Specific Aim 5 another subgroup (of each age cohort and each vaccine) will have the 2 ndblood draw at 2 weeks and the 3'd blood draw at 12 weeks after immunization.
For Specific Aim 3 another subgroup or children (of each age cohort and each vaccine) in addition to blood samples, saliva samples will be taken before vaccination and 4 weeks after immunization. Nurses will visit the children for 14 days after the vaccination to record any symptom. Cellular immunity, cytokine and measles specific IgA assays will be performed at the laboratory in Mexico City, plaque reduction neutralization assays will be performed at the National Institute of Public Health, Mexico.

National Institute of Health (NIH)
Fogarty International Center (FIC)
Research Project (R01)
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Special Emphasis Panel (ZRG1-ICP-2 (51))
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Liu, Xingzhu
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Fundacion Mexicana Para la Salud, A.C.
Mexico City
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Wong-Chew, Rosa Maria; Garcia-Leon, Miguel Leonardo; Espinosa-Torres Torrija, Bogart et al. (2011) Increasing the time of exposure to aerosol measles vaccine elicits an immune response equivalent to that seen in 9-month-old Mexican children given the same dose subcutaneously. J Infect Dis 204:426-32
Belaunzaran-Zamudio, Pablo F; Garcia-Leon, Miguel L; Wong-Chew, Rosa Maria et al. (2009) Early loss of measles antibodies after MMR vaccine among HIV-infected adults receiving HAART. Vaccine 27:7059-64
Wong-Chew, Rosa Maria; Islas-Romero, Rocio; Garcia-Garcia, Maria de Lourdes et al. (2006) Immunogenicity of aerosol measles vaccine given as the primary measles immunization to nine-month-old Mexican children. Vaccine 24:683-90