Pregnancy has a minimal impact on the acute transcriptional signature to vaccination

John S Tregoning,Cathy Maes,Christine E Jones,Stefan H E Kaufmann,January Weiner,Anna Calvert,Danielle Hake,Annelies Aerssens,Jeroen Maertzdorf,Deniz Cizmeci,Geert Leroux-Roels

doi:10.1038/s41541-020-0177-6

Abstract

Vaccination in pregnancy is an effective tool to protect both the mother and infant; vaccines against influenza, pertussis and tetanus are currently recommended. A number of vaccines with a specific indication for use in pregnancy are in development, with the specific aim of providing passive humoral immunity to the newborn child against pathogens responsible for morbidity and mortality in young infants. However, the current understanding about the immune response to vaccination in pregnancy is incomplete. We analysed the effect of pregnancy on early transcriptional responses to vaccination. This type of systems vaccinology approach identifies genes and pathways that are altered in response to vaccination and can be used to understand both the acute inflammation in response to the vaccine and to predict immunogenicity. Pregnant women and mice were immunised with Boostrix-IPV, a multivalent vaccine, which contains three pertussis antigens. Blood was collected from women before and after vaccination and RNA extracted for analysis by microarray. While there were baseline differences between pregnant and non-pregnant women, vaccination induced characteristic patterns of gene expression, with upregulation in interferon response and innate immunity gene modules, independent of pregnancy. We saw similar patterns of responses in both women and mice, supporting the use of mice for preclinical screening of novel maternal vaccines. Using a systems vaccinology approach in pregnancy demonstrated that pregnancy does not affect the initial response to vaccination and that studies in non-pregnant women can provide information about vaccine immunogenicity and potentially safety.

Highlights

Vaccination of pregnant women can protect both the mother and her offspring from infection[1].Pregnancy is associated with dynamic adaptions of the immune system throughout gestation to allow immunological tolerance of the developing foetus[2]
Changes in the number and function of immune cells have been observed, with enhanced innate immune responses, as well as reduced numbers of B cells and dendritic cells in the peripheral blood[2,3,4]. How these differences could impact the response to vaccination in pregnancy is incompletely understood, though recent studies suggest similar antibody responses to influenza and pertussis vaccination in pregnancy[5,6,7]
Having observed that immunisation with Boostrix-inactivated polio virus (IPV) induces a similar response in pregnant mice to non-pregnant mice, we investigated the response in pregnant women

Summary

INTRODUCTION

Vaccination of pregnant women (maternal vaccination) can protect both the mother and her offspring from infection[1]. Systems vaccinology has yet to be applied to immunisation in pregnancy but has the potential to make a significant contribution to this important area of vaccine research especially because of the ability to generate large data sets from smaller numbers of volunteers. Published in partnership with the Sealy Center for Vaccine Development pregnancy on the early response vaccination with Boostrix-IPV, with the changes recorded in non-pregnant mice. While this which is used in the UK to boost responses to Bordetella pertussis approach allows visualisation and subsequent gene set enrich-. Neither of these approaches showed a significant effect of pregnancy on how the mice reacted

RESULTS

Findings

DISCUSSION