Differential anti-viral response to respiratory syncytial virus A in preterm and term infantsResearch in context
Jeremy Anderson,
Samira Imran,
Yan Yung Ng,
Tongtong Wang,
Sarah Ashley,
Cao Minh Thang,
Le Quang Thanh,
Vo Thi Trang Dai,
Phan Van Thanh,
Bui Thi Hong Nhu,
Do Ngoc Xuan Trang,
Phan Thi Phuong Trinh,
Le Thanh Binh,
Nguyen Thuong Vu,
Nguyen Trong Toan,
Boris Novakovic,
Mimi L.K. Tang,
Danielle Wurzel,
Kim Mulholland,
Daniel G. Pellicci,
Lien Anh Ha Do,
Paul V. Licciardi
Affiliations
Jeremy Anderson
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Corresponding author. Murdoch Children's Research Institute, Melbourne, Australia.
Samira Imran
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia
Yan Yung Ng
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia
Tongtong Wang
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia
Sarah Ashley
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia
Cao Minh Thang
Pasteur Institute of Ho Chi Minh City, Vietnam
Le Quang Thanh
Tu Du Hospital, Ho Chi Minh City, Vietnam
Vo Thi Trang Dai
Pasteur Institute of Ho Chi Minh City, Vietnam
Phan Van Thanh
Pasteur Institute of Ho Chi Minh City, Vietnam
Bui Thi Hong Nhu
Tu Du Hospital, Ho Chi Minh City, Vietnam
Do Ngoc Xuan Trang
Tu Du Hospital, Ho Chi Minh City, Vietnam
Phan Thi Phuong Trinh
Tu Du Hospital, Ho Chi Minh City, Vietnam
Le Thanh Binh
Tu Du Hospital, Ho Chi Minh City, Vietnam
Nguyen Thuong Vu
Tu Du Hospital, Ho Chi Minh City, Vietnam
Nguyen Trong Toan
Tu Du Hospital, Ho Chi Minh City, Vietnam
Boris Novakovic
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia
Mimi L.K. Tang
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Allergy and Lung Health Unit, University of Melbourne, Melbourne, Australia
Danielle Wurzel
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Allergy and Lung Health Unit, University of Melbourne, Melbourne, Australia; Royal Children's Hospital, Melbourne, Australia
Kim Mulholland
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; London School of Hygiene and Tropical Medicine, London, United Kingdom
Daniel G. Pellicci
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia
Lien Anh Ha Do
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Corresponding author. Murdoch Children's Research Institute, Melbourne, Australia.
Paul V. Licciardi
Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Corresponding author. Murdoch Children's Research Institute, Melbourne, Australia.
Summary: Background: Preterm infants are more likely to experience severe respiratory syncytial virus (RSV) disease compared to term infants. The reasons for this are multi-factorial, however their immature immune system is believed to be a major contributing factor. Methods: We collected cord blood from 25 preterm (gestational age 30.4–34.1 weeks) and 25 term infants (gestation age 37–40 weeks) and compared the response of cord blood mononuclear cells (CBMCs) to RSVA and RSVB stimulation using neutralising assays, high-dimensional flow cytometry, multiplex cytokine assays and RNA-sequencing. Findings: We found that preterm and term infants had similar maternally derived neutralising antibody titres to RSVA and RSVB. Preterm infants had significantly higher myeloid dendritic cells (mDC) RSV infection compared to term infants. Differential gene expression analysis of RSVA stimulated CBMCs revealed enrichment of genes involved in cytokine production and immune regulatory pathways involving IL-10, IL-36γ, CXCL1, CXCL2, SOCS1 and SOCS3 in term infants, while differentially expressed genes (DEGs) in preterm infants were related to cell cycle (CDK1, TTK, ESCO2, KNL1, CDC25A, MAD2L1) without associated expression of immune response genes. Furthermore, enriched genes in term infants were highly correlated suggesting an increased co-ordination of their immune response to RSVA. When comparing DEGs in preterm and term infants following RSVB stimulation, no differences in immune response genes were identified. Interpretation: Overall, our data suggests that preterm infants have a more restricted immunological response to RSVA compared with term infants. While further studies are required, these findings may help to explain why preterm infants are more susceptible to severe RSV disease and identify potential therapeutic targets to protect these vulnerable infants. Funding: Murdoch Children's Research Institute Infection and Immunity theme grant.
