Do advanced age and allergies contribute to the reactivation of dormant herpes viruses?

What is this research project about?

Older people may suffer from weakened immune responses

What is this research project about?

Elderly individuals often show impaired adaptive immune responses towards vaccines. One underlying mechanism, called immune senescence, is a narrowing of the repertoire of immune receptors on white blood cells (B cell and T cell receptors), which reduces the flexibility of the immune system to respond to pathogens. This immune senescence may underlie secondary outbreaks of latent Varicella Zoster (VZV) infections in the elderly, which happens at a relatively high frequency of 1.5 to 5 in 1000. Interestingly, this frequency does not seem to be reduced in individuals that had been vaccinated against VZV during childhood.

What’s the current status?

Patients with atopic diseases (“allergic” diseases) are often more susceptible to viral infections. For example, a subgroup of patients suffering from atopic dermatitis (AD) shows an increased susceptibility towards herpes simplex virus (HSV-1). This disease can result in recurrent, severe and disseminated infections (“eczema herpeticum”) bearing the risk of dangerous herpes encephalitis. To address this problem, two VZV vaccines are available for adults at the moment. While a live vaccine with an attenuated strain leads to protection in about 51 % of cases, a new vaccine based on a recombinant protein in combination with two adjuvants works significantly better (>90 % protection). However, a subgroup of subjects who did not respond in clinical studies remains and this group has not been characterized to date.

Memory T lymphocytes with the ability to fight herpes viruses (Detection by flow cytometry).

What are the project goals?

The aims of this project are to address whether and to what extend immune senescence and/or an atopy-biased immune system contribute to pathologic VZV reactivation in elderly subjects. to investigate how vaccination against VZV can optimally improve the health of elderly persons.

How do we get there?

The project is based on the collection of already existing biosamples from patients with atopic dermatitis. In addition, we are currently collecting biosamples from the Zoster cohort and the HSV cohort. The samples of the RESIST study with the general population of Hannover serve as controls. Further, samples from elderly persons before and after VZV vaccination will be investigated. Here, the overall aim is to investigate anti-viral T cell responses in detail.

With our long-standing experience regarding innate and adaptive immunity and the inflammatory processes in patients suffering from AD, we are in a unique position to investigate the immune response in susceptible individuals. In previous in vitro studies involving affected patients, we found increased frequencies of T cells directed against HSV-1 that showed a probably ineffective immune response (Traidl et al. 2018). These findings suggested that the atopy-biased inflammatory milieu in these patients leads to the generation of virus-specific T cells that harbor a sub-optimal immune response against viruses. Applying our established set of methods to longitudinally characterize the dynamics of T cell responses, we aim to identify and will perform a deep phenotypical and functional characterization of pathogenic αβ as well as γδ T cells.

Lymphocytes are detected by microscopy in inflamed atopic dermatitis skin (fluorescence staining of a frozen section).


Project title: Monitoring immunity and susceptibility to herpes virus infection in senior individuals

Prof. Dr. Thomas Werfel

Projects: A3, A4, B5, RESIST-Cohort

Prof. Dr. Immo Prinz

Projects: B5, B8, B9

Prof. Dr. Reinhold Förster

Projects: B5, B9, C2

Prof. Dr. Sarina Ravens

Projects: B3, B5

PD Dr. Lennart Rösner

Projects: A3, A4, B5, RESIST-Cohort

Project B5 Publications

Publications 2022

T cell receptor sequencing specifies psoriasis as a systemic and atopic dermatitis as a skin-focused, allergen-driven disease. Roesner LM, Farag AK, Pospich R, Traidl S, Werfel T. Allergy. 2022 Mar 7.

Challenges of CRISPR-Based Gene Editing in Primary T Cells. Rezalotfi A, Fritz L, Förster R, Bošnjak B. Int J Mol Sci. 2022 Feb 1;23(3):1689.

Publications 2020

Human γδ TCR Repertoires in Health and Disease. Fichtner AS, Ravens S, Prinz I.  Cells. 2020 Mar 26;9(4):800. doi: 10.3390/cells9040800. PMID: 32225004; PMCID: PMC7226320.

Interleukin-17 cytokines: Effectors and targets in psoriasis-A breakthrough in understanding and treatment. Prinz I, Sandrock I, Mrowietz U. J Exp Med. 2020 Jan 6;217(1). pii: e20191397. doi: 10.1084/jem.20191397.

Microbial exposure drives polyclonal expansion of innate γδ T cells immediately after birth. Ravens S, Fichtner AS, Willers M, Torkornoo D, Pirr S, Schöning J, Deseke M, Sandrock I, Bubke A, Wilharm A, Dodoo D, Egyir B, Flanagan KL, Steinbrück L, Dickinson P, Ghazal P, Adu B, Viemann D, Prinz I.Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18649-18660. doi: 10.1073/pnas.1922588117. Epub 2020 Jul 20. PMID: 32690687; PMCID: PMC7414158.

RNase 7 Promotes Sensing of Self-DNA by Human Keratinocytes and Activates an Antiviral Immune Response. Kopfnagel V, Dreyer S, Baumert K, Stark M, Harder J, Hofmann K, Kleine M, Buch A, Sodeik B, Werfel T. J Invest Dermatol. 2020 Aug;140(8):1589-1598.e3. doi: 10.1016/j.jid.2019.09.029. Epub 2020 Jan 21. PMID: 31978413.

Publication 2019

Single-Cell Transcriptomics Identifies the Adaptation of Scart1(+) Vγ6(+) T Cells to Skin Residency as Activated Effector Cells. Tan L*, Sandrock I*, Odak I, Aizenbud Y, Wilharm A, Barros-Martins J, Tabib Y, Borchers A, Amado T, Gangoda L, Herold MJ, Schmidt-Supprian M, Kisielow J, Silva-Santos B, Koenecke C, Hovav AH, Krebs C, Prinz I**, Ravens S**. Cell Rep. 2019 Jun 18;27(12):3657-3671.e4.

Publications of the Project B5