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Beyond Passive Immunity: Is There Priming of the Fetal Immune System Following Vaccination in Pregnancy and What Are the Potential Clinical Implications?

ABSTRACT: Infection is responsible for over half a million neonatal deaths worldwide every year, and vaccination in pregnancy is becoming increasingly recognized as an important strategy for the protection of young infants. Increasing evidence suggests that exposure to maternal infection in utero may "prime" the developing immune system, even in the absence of infant infection. It is also possible that in utero priming may occur following maternal vaccination, with antigen-specific cellular immune responses detectable in utero and at birth. However, this remains a topic of some controversy. This review focuses on the evidence for in utero priming and the clinical implications for vaccination in pregnancy, considering whether in utero priming following vaccination could provide protection independent of antibody-mediated passive immunity, the possible effects of vaccination on subsequent infant vaccinations, their potential "non-specific" effects, and how the design and timing of vaccination might affect prenatal priming. Looking forward, we describe other possible options for quantifying antigen-specific cellular responses, including MHC tetramers, novel proliferation and cytokine-based assays, and animal models. Together, these may help us address future research questions and establish more robust evidence of fetal immune system priming.

SUBMITTER: Wilcox CR

PROVIDER: S-EPMC6054988 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Beyond Passive Immunity: Is There Priming of the Fetal Immune System Following Vaccination in Pregnancy and What Are the Potential Clinical Implications?

Wilcox Christopher R CR Jones Christine E CE

Frontiers in immunology 20180716

Infection is responsible for over half a million neonatal deaths worldwide every year, and vaccination in pregnancy is becoming increasingly recognized as an important strategy for the protection of young infants. Increasing evidence suggests that exposure to maternal infection <i>in utero</i> may "prime" the developing immune system, even in the absence of infant infection. It is also possible that <i>in utero</i> priming may occur following maternal vaccination, with antigen-specific cellular ...[more]

PMID: 30061881

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Project description:Infection during pregnancy can lead to activation of the maternal immune system and has been associated with an increased risk of having an offspring later diagnosed with a neurodevelopmental disorders (NDD) such as autism spectrum disorder (ASD) or schizophrenia (SZ). Most maternal immune activation (MIA) studies to date have been in rodents and usually involve the use of lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C). However, since NDD are based on behavioral changes, a model of MIA in non-human primates could potentially provide data that helps illuminate complex behavioral and immune outputs in human NDD. In this study twenty-one pregnant rhesus macaques were either given three injections over 72 hours of poly I:C-LC, a double stranded RNA analog (viral mimic), or saline as a control. Injections were given near the end of the first trimester or near the end of the second trimester to determine if there were differences in immune output due to the timing of MIA.An additional three non-treated animals were used as controls. The offspring were followed until 4 years of age, with blood collected at the end of their first (year 1) and fourth (year 4) years to assess dynamic cellular immune function. Induced responses from peripheral immune cells were measured using multiplex assays.At one year of age, MIA exposed offspring displayed elevated production of innate inflammatory cytokines including: interleukin (IL)-1β, IL-6, IL-12p40, and tumor necrosis factor (TNF)α at baseline and following stimulation. At four years of age, the MIA exposed offspring continued to display elevated IL-1β, and there was also a pattern of an increased production of T-cell helper type (TH)-2 cytokines, IL-4 and IL-13. Throughout this time period, the offspring of MIA treated dams exhibited altered behavioral phenotypes including increased stereotyped behaviors. During the first two years, stereotyped behaviors were associated with innate cytokine production. Self-directed behaviors were associated with TH2 cytokine production at year 4. Data from this study suggests long-term behavioral and immune activation was present in offspring following MIA. This novel non-human primate model of MIA may provide a relevant clinically translational model to help further elucidate the role between immune dysfunction and complex behavioral outputs following MIA.

Dataset Information

Beyond Passive Immunity: Is There Priming of the Fetal Immune System Following Vaccination in Pregnancy and What Are the Potential Clinical Implications?

Publications

Beyond Passive Immunity: Is There Priming of the Fetal Immune System Following Vaccination in Pregnancy and What Are the Potential Clinical Implications?

Similar Datasets

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