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

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 nonpregnant 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.npj Vaccines (2020) 5:29 ; https://doi.

Is the Host Viral Response and the Immunogenicity of Vaccines Altered in Pregnancy?

“…A recent study carried out by Tregoning et al investigated the effect of pregnancy on the transcriptomic response after vaccination in pregnant and non-pregnant mouse models and from humans. They also found no difference between the pregnant and non-pregnant state at the level of individual genes, and found similar levels of inflammation post vaccination in both mice models and humans [118]. Kay et al, also demonstrated that pregnant women were able to induce a robust plasmablast response following vaccination as these women had an equivalent rate of post vaccination HAI titres and seroprotection when compared to non-pregnant women [119].…”

Maternal Immunization: Nature Meets Nurture

“…Novel approaches include the study of high-dimensional cell-subset immunophenotyping through CyTOF (Porpiglia et al, 2017;Lingblom et al, 2018;Reeves et al, 2018) and vaccine-induced changes at the metabolic (Li et al, 2017) proteomic (Galassie and Link, 2015) genetic and transcriptional (Stubbington et al, 2017) levels. This knowledge is largely being harnessed to establish signatures predictive of vaccine immunogenicity (Pezeshki et al, 2019), although early inflammatory transcriptomic profiling has recently been explored in the context of vaccine safety (Tregoning et al, 2020). Systems serology has also been used to define Fc features associated with antibody transfer and effector function, as discussed previously (Chung and Alter, 2017;Jennewein et al, 2019) including a detailed characterization of adjuvant effects on antibody quality (Francica et al, 2017).…”

“…Conversely, a systems vaccinology approach can help to understand the effect of pregnancy itself on vaccination, including the specific acute inflammatory pathways induced and markers of immunogenicity/safety. Using Boostrix vaccine (combined diphtheria, tetanus, multivalent acellular pertussis), Tregoning et al (2020) demonstrated that pregnancy might have minimal impact on initial vaccine-induced responses; they observed characteristic patterns of gene expression, BOX 2 | Gaps in knowledge and future avenues of research in infants.…”

“…including upregulation in interferon response and innate immunity gene modules that were independent of pregnancy, irrespective of baseline differences and similar in both women and mice. Given this, they propose that studies in non-pregnant women can provide information about maternal vaccine immunogenicity and potentially safety; using murine models may also be promising in this context (Tregoning et al, 2020). Therefore, it is hoped that newer 'omics' assays may elucidate key mechanisms controlling vaccine immunity, particularly functional responses, define molecular signatures, identify novel CoP and predict clinical end-points, including safety.…”

“…Conversely, a systems vaccinology approach can help to understand the effect of pregnancy itself on vaccination, including the specific acute inflammatory pathways induced and markers of immunogenicity/safety. Using Boostrix vaccine (combined diphtheria, tetanus, multivalent acellular pertussis), Tregoning et al (2020) demonstrated that pregnancy might have minimal impact on initial vaccine-induced responses; they observed characteristic patterns of gene expression, including upregulation in interferon response and innate immunity gene modules that were independent of pregnancy, irrespective of baseline differences and similar in both women and mice. Given this, they propose that studies in non-pregnant women can provide information about maternal vaccine immunogenicity and potentially safety; using murine models may also be promising in this context ( Tregoning et al, 2020 ).…”