Infants are at increased risk for serious complications from influenza, with morbidity rates exceeding even adults >65 years. Unfortunately, influenza vaccines are ineffective in infants <6 months of age. This biologically vulnerable group relies on maternal antibody for protection. Public health officials advocate maternal immunization;however, there is no data on which type of maternal influenza vaccine best protects infants. We seek to compare maternal response to the systemic inactivated influenza vaccine (TIV) and the intranasal live-attenuated influenza vaccine (LAIV). Because the lactating mammary gland is part of mucosa-associated lymphoid tissue, we hypothesize that mucosally-administered LAIV will elicit higher levels of anti-influenza immunity in breast milk than vaccination with the injeced TIV. We will evaluate levels of influenza-specific antibodies and cellular immunity in blood and breast milk. We also will compare levels of influenza-specific responses in TIV and LAIV recipients. Finally, we will perform gene expression experiments to identify gene expression patterns induced after vaccination to further understand differences in innate and adaptive immune responses. Our data will provide a comprehensive analysis of the mechanisms underlying immune protection during breastfeeding. Moreover, the experience and knowledge gained from this proposal will lay the foundation for an R01 application for support for further investigations of how to optimize this maternal vaccination strategy for the protection of infants against influenza and other infectious diseases.

Public Health Relevance

Maternal immunization with influenza vaccine has the potential to protect infants less than six months of age, a vulnerable age group at risk for seriou complications and death and for whom vaccine is not available. This proposal seeks to evaluate the immune response in breast milk following maternal immunization with the injected inactivated influenza vaccine compared to the nasal spray live attenuated influenza vaccine. The results will increase our understanding of how breast milk provides immune protection and will lay the foundation for larger clinical studies to determine which maternal immunization strategy is most efficacious in protecting infants.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23HD072774-01A1
Application #
8581655
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Raiten, Daniel J
Project Start
2013-08-14
Project End
2018-05-31
Budget Start
2013-08-14
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$133,515
Indirect Cost
$9,815
Name
Children's Hospital of Los Angeles
Department
Type
DUNS #
052277936
City
Los Angeles
State
CA
Country
United States
Zip Code
90027
Pannaraj, Pia S; Wang, Hai-Lin; Rivas, Hector et al. (2014) School-located influenza vaccination decreases laboratory-confirmed influenza and improves school attendance. Clin Infect Dis 59:325-32