Protection of at-risk low birth weight infants against influenza via maternal antibody

通过母源抗体保护高危低出生体重婴儿免受流感侵害

• 批准号: 10621718
• 负责人: Alisa Kachikis
• 金额: $ 18.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621718
• 关键词: 2019-nCoV; Acute respiratory infection; Affect; Antibodies; Antibody titer measurement; Antigens; Biophysics; COVID-19 vaccine; Chorionic villi; Clinical; Clinical Trials; Cohort Studies; Communicable Diseases; Computational Biology; Computer Analysis; Dedications; Development; Discipline of obstetrics; Effector Cell; Enzyme-Linked Immunosorbent Assay; Fc Receptor; Fetus; Gestational Age; Goals; High-Risk Pregnancy; Immune; Immunity; Immunization Programs; Immunoglobulin G; Immunohistochemistry; Immunology; Impairment; Incidence; Infant; Infection; Infection prevention; Inflammatory; Influenza; Knowledge; Low Birth Weight Infant; Lytic; Maternal antibody; Mentorship; Methods; Modeling; Mothers; Nature; Neonatal; Neonatal Mortality; Pathology; Perinatal mortality demographics; Physicians; Placenta; Placental Insufficiency; Plasma; Population; Predisposition; Pregnancy; Pregnancy Complications; Pregnant Women; Prevention strategy; Process; Qualifying; Research; Research Personnel; Research Training; Resource-limited setting; Respiratory Disease; Respiratory Tract Infections; Risk; Sampling; Scientist; Serology; Shapes; Small for Gestational Age Infant; Statistical Data Interpretation; Syncytiotrophoblast; System; Testing; Training; Training Programs; Umbilical Cord Blood; Vaccinated; Vaccination; Vaccines; Woman; antibody test; antibody transfer; biophysical properties; burden of illness; career; cohort; fetal; global health; high risk; high risk population; immune function; improved; influenza virus vaccine; innovation; insight; maternal vaccination; mortality; neonatal Fc receptor; neonatal immune system; neonatal immunity; neonatal infection; neonate; novel; novel strategies; novel vaccines; pathogen; placental morphology; placental transfer; premature; programs; prospective; receptor expression; respiratory; respiratory pathogen; respiratory virus; skills; statistics; success; translational research program; vaccination strategy; vaccine delivery; vaccinology; virology

PROJECT SUMMARY / ABSTRACT Acute respiratory infections are the leading cause of mortality among neonates globally, particularly among low birthweight infants from pregnancies complicated by prematurity or placental insufficiency. Maternal immuniza- tion, the vaccination of pregnant women to enhance antibody transported across the placenta to the fetus, is utilized increasingly as an infection prevention strategy to protect neonates from pathogens such as influenza, and may be critical as new vaccines against SARS-CoV-2 are developed. This proposal aims to better eluci- date transplacental antibody transfer in low- and high-risk pregnancies, specifically those with prematurity or placental insufficiency, which is not known. It also describes a research training program that will allow me to become an independent physician-scientist with a translational research program focusing on infectious diseases and vaccines in pregnancy. This proposal builds upon my training in high-risk obstetrics and global health, and provides a detailed plan to improve my knowledge of virology, immunology, vaccinology, cohort studies and statistical analysis. It incorporates the expertise of an outstanding mentorship team, including experts in infectious diseases, immunology, pathology, statistics, and computational biology who are dedicated to the success of this project and the development of my career as an independent clinical researcher. The first aim of this proposal involves establishing normal and high-risk pregnancy cohorts and quantifying transplacental antibody transfer in the context of pregnancies resulting in both normal and low birth weight infants, including those complicated by placental insufficiency leading to small for gestational age infants or prematurity. I will compare quantity of transplacental antibody transfer of total IgG, influenza- and SARS-CoV- 2- specific antibodies, and expression of neonatal Fc receptor in placentas. I will also compare neonatal immunity against influenza among women who did and did not receive influenza vaccine during pregnancy, allowing the opportunity to develop multivariable models and adjust for multiple clinical covariates. For my second aim, I will characterize antibody profiles and transplacental transfer in the same cohorts using a systems serology approach to determine biophysical and effector functions of maternal and fetal immunology. Through accomplishing the aims in this proposal, I will contribute significantly to our knowledge of maternal immunizations, maternal and neonatal immune interactions and neonatal immunity against influenza and SARS-CoV-2. Improved understanding and characterization of transplacental antibody transfer in the context of maternal immunizations may provide insight in the optimization and individualization of vaccine delivery and timing in high-risk pregnancies and, ultimately, has the potential to improve neonatal survival globally. This proposal will allow me to develop a unique set of cross-disciplinary skills and expertise in order to transition to independence as a physician scientist with a larger research program specializing in respiratory infectious diseases and vaccines within the context of low- and high-risk pregnancies.

项目摘要/摘要

项目成果

Risk Factors Associated with Congenital Syphilis, Georgia, 2008-2015.

• DOI: 10.1155/2023/3958406
• 发表时间: 2023
• 期刊: Infectious diseases in obstetrics and gynecology
• 作者: Kachikis, Alisa;Schiff, Melissa A;Moore, Kathryn;Chapple-McGruder, Theresa;Arluck, Jessica;Hitti, Jane
• 通讯作者: Hitti, Jane

Hybrid Immunity to Severe Acute Respiratory Syndrome Coronavirus 2 During Pregnancy Provides More Durable Infant Antibody Responses Compared to Natural Infection or Vaccination Alone.

与自然感染或单独接种疫苗相比，怀孕期间对严重急性呼吸系统综合症冠状病毒 2 的混合免疫可提供更持久的婴儿抗体反应。

• DOI: 10.1093/infdis/jiae046
• 发表时间: 2024
• 期刊: The Journal of infectious diseases
• 作者: LaCourse,SylviaM;Wetzler,EricaA;Aurelio,MorganC;Escudero,JaclynN;Selke,StacyS;Greninger,AlexanderL;Goecker,ErinA;Barnes,SarinaR;Arnould,IsabelS;Pérez-Osorio,AilynC;Richardson,BarbraA;Kachikis,Alisa;Englund,JanetA;Drak
• 通讯作者: Drak

Timing of Maternal COVID-19 Vaccine and Antibody Concentrations in Infants Born Preterm.

• DOI: 10.1001/jamanetworkopen.2023.52387
• 发表时间: 2024-01-02
• 期刊: JAMA NETWORK OPEN
• 影响因子: 13.8
• 作者: Kachikis, Alisa;Pike, Mindy;Eckert, Linda O.;Roberts, Emma;Frank, Yael;Young, Amber L.;Goecker, Erin;Gravett, Michael G.;Greninger, Alexander L.;Englund, Janet A.
• 通讯作者: Englund, Janet A.

Infectious Diseases in Obstetrics and Gynecology: Moving Forward in the Twenty-First Century.

妇产科传染病：二十一世纪的前进。

• DOI: 10.1016/j.ogc.2023.02.001
• 发表时间: 2023
• 期刊: Obstetrics and gynecology clinics of North America
• 影响因子: 3.2
• 作者: Ault,KevinA;Kachikis,AlisaB
• 通讯作者: Kachikis,AlisaB

Severe acute respiratory syndrome coronavirus 2 seroprevalence and longitudinal antibody response following natural infection in pregnancy: A prospective cohort study.

• DOI: 10.1177/17455057231190955
• 发表时间: 2023-01
• 期刊: WOMENS HEALTH
• 影响因子: 2.4
• 作者: Drake, Alison L.;Escudero, Jaclyn N.;Aurelio, Morgan C.;Wetzler, Erica A.;Ellington, Sascha R.;Zapata, Lauren B.;Galang, Romeo R.;Snead, Margaret C.;Yamamoto, Krissy;Salerno, Carol C.;Richardson, Barbra A.;Greninger, Alexander L.;Kachikis, Alisa B.;Englund, Janet A.;Lacourse, Sylvia M.
• 通讯作者: Lacourse, Sylvia M.