Seasonal trivalent influenza virus vaccine (TIV) is recommended for all pregnant women because they are considered at high risk for complications, hospitalization, and death from influenza. Vaccination in pregnancy can also provide protection for infants from 0-6 months, a high risk group for whom vaccination is not approved. However, there are virtually no data on predictors of adequate maternal antibody response or sufficient antibody transfer to the newborn. Studies of nonpregnant adults and animals as well as our own preliminary data on antibody responses following TIV in pregnant women demonstrate that psychosocial stress and obesity are two key risk factors that warrant attention in this regard. Study Design: We will examine effects of psychosocial stress and obesity on 1) antibody responses to TIV in pregnant women and 2) antibody transfer from the mother to the newborn. This study will include 180 women (90 obese, 90 non-obese) who will be vaccinated during the 2nd trimester of pregnancy (13-28 weeks gestation). Maternal antibody levels will be assessed prior to vaccination, at one month post-vaccination and at the time of delivery. Newborn antibody levels will be measured via cord blood at the time of delivery. Data will be collected across three influenza seasons. In each season, 60 women will be assessed; 30 obese and 30 non-obese who will be similar in age, race, parity, and socioeconomic status. Anti-influenza antibody titers to A/H1N1, A/H3N2, and B strains in each year will be determined by the hemagglutination inhibition (HAI) test. Hypothesis 1: Among pregnant women, both stress and obesity will predict decreased likelihood of achieving a protective antibody response at one month after TIV. Effects of obesity will be the most pronounced among highly stressed women. Hypothesis 2: Greater maternal stress and obesity will predict decreased likelihood of protective antibody levels in newborn cord blood, with the most robust effects among those with both risk factors. We will examine four pathways which may contribute to effects in newborns: 1) impaired magnitude of maternal antibody response (Hypothesis 1), 2) poorer maintenance of maternal antibody levels from one month post-vaccination to delivery, 3) less efficient maternal-fetal transmission (newborn cord blood/maternal antibody ratio), and 4) higher rates of preterm birth. This study tests the innovative hypotheses that psychosocial stress and obesity substantially impair maternal antibody responses and antibody levels in newborns following maternal influenza vaccination in pregnancy. If our hypotheses are confirmed, we will identify and quantify the impact of novel risk factors for poor immune protection in two populations vulnerable to influenza complications, pregnant women and infants. High dose vaccine or two dose schedules are now available for other high risk groups who show poor responses to traditional TIV including older adults, children, and transplant recipients. This study will determine if it is justified to re-evaluate influenza vaccine recommendations for pregnant women with specific risk factors.

Public Health Relevance

This study tests the innovative hypotheses that psychosocial stress and obesity substantially impair maternal antibody responses and antibody levels in newborns following maternal influenza vaccination in pregnancy. If our hypotheses are confirmed, we will identify and quantify the impact of novel risk factors for poor immune protection from vaccination in two populations vulnerable to influenza complications, pregnant women and infants. High dose vaccine or two dose schedules are now available for other high risk groups who show poor responses to traditional TIV including older adults, children, and transplant recipients. This study will determine if it is justified to re-evaluate influenza vaccin recommendations for pregnant women with specific risk factors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Nursing Research (NINR)
Type
Research Project (R01)
Project #
5R01NR013661-05
Application #
9305779
Study Section
Nursing and Related Clinical Sciences Study Section (NRCS)
Program Officer
Yoon, Sung Sug
Project Start
2013-08-07
Project End
2019-07-31
Budget Start
2017-08-01
Budget End
2019-07-31
Support Year
5
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Ohio State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Finy, M Sima; Christian, Lisa M (2018) Pathways linking childhood abuse history and current socioeconomic status to inflammation during pregnancy. Brain Behav Immun 74:231-240
Mitchell, Amanda M; Kowalsky, Jennifer M; Epel, Elissa S et al. (2018) Childhood adversity, social support, and telomere length among perinatal women. Psychoneuroendocrinology 87:43-52
Mitchell, Amanda M; Porter, Kyle; Christian, Lisa M (2018) Examination of the role of obesity in the association between childhood trauma and inflammation during pregnancy. Health Psychol 37:114-124
Christian, Lisa M; Kowalsky, Jennifer M; Mitchell, Amanda M et al. (2018) Associations of postpartum sleep, stress, and depressive symptoms with LPS-stimulated cytokine production among African American and White women. J Neuroimmunol 316:98-106
Christian, Lisa M; Beverly, Chloe; Mitchell, Amanda M et al. (2017) Effects of prior influenza virus vaccination on maternal antibody responses: Implications for achieving protection in the newborns. Vaccine 35:5283-5290
Mitchell, Amanda M; Palettas, Marilly; Christian, Lisa M (2017) Fetal sex is associated with maternal stimulated cytokine production, but not serum cytokine levels, in human pregnancy. Brain Behav Immun 60:32-37
Mitchell, Amanda M; Christian, Lisa M (2017) Financial strain and birth weight: the mediating role of psychological distress. Arch Womens Ment Health 20:201-208
Gillespie, Shannon L; Porter, Kyle; Christian, Lisa M (2016) Adaptation of the inflammatory immune response across pregnancy and postpartum in Black and White women. J Reprod Immunol 114:27-31
Gillespie, Shannon L; Christian, Lisa M (2016) Body Mass Index as a Measure of Obesity: Racial Differences in Predictive Value for Health Parameters During Pregnancy. J Womens Health (Larchmt) 25:1210-1218
Christian, Lisa M; Porter, Kyle; Karlsson, Erik et al. (2015) Proinflammatory cytokine responses correspond with subjective side effects after influenza virus vaccination. Vaccine 33:3360-6

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