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

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@article{823437d4604a4f97aae7785507d12e6c,
title = "Investigating the aetiology of adverse events following HPV vaccination with systems vaccinology",
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-na{\"i}ve 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.",
keywords = "Chronic fatigue syndrome/myalgic encephalomyelitis, Systems biology, Vaccine safety, ‘Omics technologies, Immunogenicity, Vaccine, Papillomaviridae/immunology, Vaccination/adverse effects, Humans, Papillomavirus Vaccines/adverse effects, Papillomavirus Infections/epidemiology, Computational Biology/methods, Animals, Vaccinology/methods, Virion/immunology",
author = "Joan Campbell-Tofte and Aristidis Vrahatis and Knud Josefsen and Jesper Mehlsen and Kaj Winther",
year = "2019",
month = "1",
doi = "10.1007/s00018-018-2925-6",
language = "English",
volume = "76",
pages = "67--87",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
publisher = "Birkhaeuser Verlag AG",
number = "1",

}

RIS

TY - JOUR

T1 - Investigating the aetiology of adverse events following HPV vaccination with systems vaccinology

AU - Campbell-Tofte, Joan

AU - Vrahatis, Aristidis

AU - Josefsen, Knud

AU - Mehlsen, Jesper

AU - Winther, Kaj

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

KW - Chronic fatigue syndrome/myalgic encephalomyelitis

KW - Systems biology

KW - Vaccine safety

KW - ‘Omics technologies

KW - Immunogenicity, Vaccine

KW - Papillomaviridae/immunology

KW - Vaccination/adverse effects

KW - Humans

KW - Papillomavirus Vaccines/adverse effects

KW - Papillomavirus Infections/epidemiology

KW - Computational Biology/methods

KW - Animals

KW - Vaccinology/methods

KW - Virion/immunology

U2 - 10.1007/s00018-018-2925-6

DO - 10.1007/s00018-018-2925-6

M3 - Review

VL - 76

SP - 67

EP - 87

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

IS - 1

ER -

ID: 55617043