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Investigating the aetiology of adverse events following HPV vaccination with systems vaccinology

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Abstract

In contrast to the insidious and poorly immunogenic human papillomavirus (HPV) infections, vaccination with the HPV virus-like particles (vlps) is non-infectious and stimulates a strong neutralizing-antibody response that protects HPV-naïve vaccinees from viral infection and associated cancers. However, controversy about alleged adverse events following immunization (AEFI) with the vlps have led to extensive reductions in vaccine acceptance, with countries like Japan dropping it altogether. The AEFIs are grouped into chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). In this review, we present a hypothesis that the AEFIs might arise from malfunctions within the immune system when confronted with the unusual antigen. In addition, we outline how the pathophysiology of the AEFIs can be cost-effectively investigated with the holistic principles of systems vaccinology in a two-step process. First, comprehensive immunological profiles of HPV vaccinees exhibiting the AEFIs are generated by integrating the data derived from serological profiling for prominent HPV antibodies and serum cytokines, with data from serum metabolomics, peripheral white blood cells transcriptomics and gut microbiome profiling. Next, the immunological profiles are compared with corresponding profiles generated for matched (a) HPV vaccinees without AEFIs; (b) non-HPV-vaccinated individuals with CFS/ME-like symptoms; and (c) non-HPV-vaccinated individuals without CFS/ME. In these comparisons, any causal links between HPV vaccine and the AEFIs, as well as the underlying molecular basis for the links will be revealed. Such a study should provide an objective basis for evaluating HPV vaccine safety and for identifying biomarkers for individuals at risk of developing AEFI with HPV vaccination.

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Abbreviations

HPV:

Human papillomavirus

AEFI:

Adverse events following immunization

CFS/ME:

Chronic fatigue syndrome/myalgic encephalomyelitis

DC:

Dendritic cells

APC:

Antigen-presenting cell

BCR:

B cell receptor

TCR:

T cell receptor

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Authors and Affiliations

  1. Gaudeo-IK, Gentofte, Denmark

    Joan Campbell-Tofte

  2. Department of Medical Physics, University of Patras, Patras, Greece

    Aristidis Vrahatis

  3. Bartholin Institute, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen Ø, Denmark

    Knud Josefsen

  4. Coordinating Research Centre, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, 2000, Frederiksberg, Denmark

    Jesper Mehlsen

  5. Department of Nutrition, Exercise and Sports, University of Copenhagen, Nørre Allé 51, DK-2200, Copenhagen N, Denmark

    Kaj Winther

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  1. Joan Campbell-Tofte
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  4. Jesper Mehlsen
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  5. Kaj Winther
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Correspondence to Joan Campbell-Tofte.

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Campbell-Tofte, J., Vrahatis, A., Josefsen, K. et al. Investigating the aetiology of adverse events following HPV vaccination with systems vaccinology. Cell. Mol. Life Sci. 76, 67–87 (2019). https://doi.org/10.1007/s00018-018-2925-6

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