Leukocyte transcript alterations in West-African girls following a booster vaccination with diphtheria-tetanus-pertussis vaccine

Abstract

Background. Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. Methods. To investigate possible changes in gene expression after DTP vaccination, we identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. As a pilot experiment we extracted RNA from blood samples before, and 6 weeks after, vaccination to analyze the coding transcriptome in leukocytes using expression microarrays, and ended up with information from eight girls. The data was further analyzed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. Results. We found very few transcripts to alter systematically. Those that did mainly belonged to the Interferon (IFN) signalling pathway. We scrutinized this pathway as well as the Interleukin (IL) pathways. Two out of eight showed a down-regulated IFN pathway and two showed an up-regulated IFN pathway. The two with down-regulated IFN pathway had also down-regulated IL-6 pathway. In the study of networks, two of the girls stood out as not having the inflammatory response as top altered network. Conclusion. The transcriptome changes following DTP booster vaccination were subtle, but although the material was small, it was possible to identify sub groups that deviate from each other, mainly in the IFN response.

Key Words::

• Immunology
• mortality
• pediatrics
• gene expression
• vaccine
• microarrays

Acknowledgements

We acknowledge the following for helpful discussions: Jesper Melchjorsen, Department of Infectious Diseases, Aarhus University Hospital, Skejby, Denmark; Torben Ørntoft, Dept. of Molecular Medicine, Aarhus University Hospital, Skejby, Denmark.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the article. Christine Benn is funded by ERC (ERC-2009-StG, grant agreement no. 243149) and by the Danish National Research Foundation (DNRF108).