Transplacental and Breast Milk Transfer of IgG1 Are Both Required for Prolonged Protection of Offspring Against Influenza A Infection.

Julia Chronopoulos,Maziar Divangahi,James G Martin

doi:10.3389/fimmu.2022.823207

Julia Chronopoulos, Maziar Divangahi + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2022.823207

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Abstract

The immune system during pregnancy teeters between maintaining fetal tolerance and providing protection against pathogens. Due to this delicate balance, pregnant women and their offspring often have increased susceptibilities to infection. During the first year of life, infant immunity against infection is mainly mediated via passively transferred maternal antibodies. However, our understanding of the route of transfer of the maternal antibodies for conferring protection to influenza A virus (IAV) infection in offspring is incomplete. Here we have demonstrated that offspring from IAV-infected mice were significantly protected against IAV infection. This remarkable increase in survival is mediated via the elevated maternal serum IgG1. By cross-fostering, we further showed that this enhanced host resistance was only achieved in mice born to and nursed by IAV-infected mothers. Collectively, our data suggest that the prolonged protection of offspring against IAV infection requires maternal IgG1 from both the placenta and breast milk.

Highlights

Pregnancy has been long thought of as a state of immunosuppression, emerging evidence is drawing attention to unique and dynamic processes that differently influence the severity of maternal responses to infectious disease and vaccine outcomes [1, 2]
Using a model of mid-gestation influenza A virus (IAV) infection and pre-conception infection, we have provided evidence that offspring born to IAV-infected mothers are significantly protected against IAV infection
Antibodies were assessed in naïve offspring at 4 and 8 weeks after birth as well as the immune response to secondary IAV infection at 8 weeks (Figure 1A)

Summary

Introduction

Pregnancy has been long thought of as a state of immunosuppression, emerging evidence is drawing attention to unique and dynamic processes that differently influence the severity of maternal responses to infectious disease and vaccine outcomes [1, 2]. Infants under one year of age are at the highest risk of increased morbidity and hospitalization following infection with pathogens like influenza A virus (IAV), vaccination is recommended but only beyond 6 months of age [3] [4]. During this vaccination gap when children are immunologically immature and harbor a respiratory system that is still developing, maternal immunoglobulins (Ig) are critical for conferring protection against pathogens [5]. In humans, Influenza Infection, Pregnancy, and IgG1 maternal vaccination during the second and early third trimester yields higher antibody titers in cord blood and prolongs the window of protection in offspring against influenza and pertussis [8, 9]. Public health strategies, especially during the current COVID-19 pandemic, are reinforcing the basis that maternally transferred antibodies can protect newborns from potentially fatal respiratory illness [8, 10, 11]

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