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Transcriptomic profiles of high and low antibody responders to smallpox vaccine

Genes & Immunity volume 14, pages 277–285 (2013)Cite this article

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Abstract

Despite its eradication over 30 years ago, smallpox (as well as other orthopox viruses) remains a pathogen of interest both in terms of biodefense and for its use as a vector for vaccines and immunotherapies. Here we describe the application of mRNA-Seq transcriptome profiling to understanding immune responses in smallpox vaccine recipients. Contrary to other studies examining gene expression in virally infected cell lines, we utilized a mixed population of peripheral blood mononuclear cells in order to capture the essential intercellular interactions that occur in vivo, and would otherwise be lost, using single cell lines or isolated primary cell subsets. In this mixed cell population we were able to detect expression of all annotated vaccinia genes. On the host side, a number of genes encoding cytokines, chemokines, complement factors and intracellular signaling molecules were downregulated upon viral infection, whereas genes encoding histone proteins and the interferon response were upregulated. We also identified a small number of genes that exhibited significantly different expression profiles in subjects with robust humoral immunity compared with those with weaker humoral responses. Our results provide evidence that differential gene regulation patterns may be at work in individuals with robust humoral immunity compared with those with weaker humoral immune responses.

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Acknowledgements

We gratefully acknowledge the subjects who participated in this study. We wish to thank the nurses, phlebotomists and study coordinators at both the Naval Health Research Center and the Mayo Clinic—particularly, Dr Meg Ryan for her time and efforts in subject recruitment, and Shaun Riska, Sumit Middha and Asha Nair for biostatistical and bioinformatics support. This study was supported by the National Institutes of Health contract HHSN266200400065C (AI40065).

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Authors and Affiliations

  1. Mayo Vaccine Research Group, Mayo Clinic, Rochester, MN, USA

    R B Kennedy, A L Oberg, I G Ovsyannikova, I H Haralambieva, D Grill & G A Poland

  2. Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, MN, USA

    R B Kennedy, I G Ovsyannikova, I H Haralambieva & G A Poland

  3. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA

    A L Oberg & D Grill

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  1. R B Kennedy
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Correspondence to G A Poland.

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Competing interests

Dr Poland is the chair of a Safety Evaluation Committee for investigation vaccine trials being conducted by Merck Research Laboratories. Dr Poland offers consultative advice to Merck & Co. Inc, CSL Biotherapies, Avianax, Sanofi Pasteur, Dynavax, Novartis Vaccines and Therapeutics, and PAXVAX Inc. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. The content is the sole responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. The remaining authors declare no conflict of interest.

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Kennedy, R., Oberg, A., Ovsyannikova, I. et al. Transcriptomic profiles of high and low antibody responders to smallpox vaccine. Genes Immun 14, 277–285 (2013). https://doi.org/10.1038/gene.2013.14

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