Letter to the Editor: Proposal for Th1-Induction Therapy for Atopic Dermatitis: A Possibility for the Use of the Varicella Zoster Virus Vaccine

To the Editor:

Atopic dermatitis (AD) (Kim et al, 2019) is an allergic skin disorder, caused by various environmental factors, such as mite, with a complex pathology, including mainly T helper type (Th)2 dominant conditions. Lower interferon-gamma (IFN-γ) protein production is also significant (Katsunuma et al, 2004). Unfortunately, despite the vast amount of research, the mechanisms of genetically impaired immune response and protective response to infectious pathogens are still not well defined in patients with atopy, and a definitive and reliable treatment has not yet been found (Kim et al, 2019). In humans, an improvement in severe atopic skin lesions after the onset of varicella has been observed (Fujimura et al, 1997).

Fujimura et al (1997) showed that a switch from Th2 to Th1 regulation can affect patients suffering from varicella, thereby supporting the observations of AD symptom amelioration after varicella infection. So far, the potential of the varicella–zoster virus (VZV) vaccine (Levin and Weinberg, 2019) for AD treatment was considered.

Studies investigating the effects of the VZV vaccine have examined live VZV vaccines, inactivated (nonlive) zoster vaccines (ZVI), the attenuated VZV vaccine (Oka/Merck; inactivated by heat or irradiation), and recombinant glycoprotein E-adjuvanted HZ vaccines (RZV) (Levin and Weinberg, 2019). Certain herpes virus components, such as VZV glycoproteins (gpI–V), the immediate early/tegument protein, and the product of gene 62 (IE62) can regulate such Th1 responses by activated CD4⁺ Th1 cells (Zerboni et al, 2014).

Furthermore, the vaccine-induced IFN-γ expression in VZV-specific T cell-mediated responses can be activated and enhanced by the attenuated VZV vaccine (Oka/Merck) by recruiting polyfunctional VZV-specific CD4⁺ and CD8⁺ T cells (Levin and Weinberg, 2019). It has been established that Th1 induction lasts for 4 to 6 months in varicella patients (Fujimura et al, 1997). In addition, the protective immune response against infection by the VZV vaccine lasts for 4–6 months (Levin and Weinberg, 2019). Based on these findings, it may be worthwhile to use the VZV vaccine as a vaccination agent not only to protect against infection but also for immunostimulation with Th1 induction.

For example, the attenuated live vaccine was administered to patients with refractory severe AD and bacterial contact dermatitis to prevent herpes zoster, but no particular improvement was seen. This may not be expected, but it cannot be used to prevent aggravation. The author believes that the VZV vaccine should be considered a basis of immunity to control the Th2 response and to induce and maintain the Th1 response. However, how Th1 responses contribute to the pathogenesis of atopy in Th2 pathology is controversial. It is possible to modify the immune response of atopic diseases in a Th2-dominant state to more Th1 and apply the VZV vaccine as a basis for symptom improvement. There have been few in vitro studies of the regulatory response of the VZV vaccine for atopic conditions.

Based on the findings described so far, the Th1 response evoked by the defense mechanism against VZV infection is useful in controlling the allergic hypersensitivity response (Horiuchi, 2022). If we can find a component that induces and maintains the Th1 state, it may lead to the development of a drug for maintaining Th1 homeostasis while suppressing the activation of Th2 responses.