Mucosal vs Systemic Influenza Vaccine While Breastfeeding: Milk Immunity

描述（由申请人提供）：婴儿患流感严重并发症的风险增加，发病率甚至超过65岁以上的成年人。不幸的是，流感疫苗对6个月以下的婴儿无效。这一生物学上的弱势群体依赖于母体抗体的保护。公共卫生官员提倡母亲接种疫苗;然而，没有数据表明哪种类型的母亲流感疫苗最能保护婴儿。我们试图比较母体对全身灭活流感疫苗（TIV）和鼻内减毒活流感疫苗（LAIV）的反应。由于泌乳期乳腺是粘膜相关淋巴组织的一部分，我们假设粘膜接种LAIV将比注射TIV疫苗在母乳中引起更高水平的抗流感免疫。我们将评估血液和母乳中流感特异性抗体和细胞免疫水平。我们还将比较TIV和LAIV接受者的流感特异性应答水平。最后，我们将进行基因表达实验，以确定疫苗接种后诱导的基因表达模式，以进一步了解先天性和适应性免疫反应的差异。我们的数据将对母乳喂养期间免疫保护的机制进行全面分析。此外，从该提案中获得的经验和知识将为R 01申请奠定基础，以支持进一步研究如何优化该孕产妇疫苗接种策略，以保护婴儿免受流感和其他传染病的侵害。

DESCRIPTION (provided by applicant): 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.