Novel Injection Dose and Delivery of Varicella-Zoster Virus Vaccine

syringe and a couple vials
syringe and a couple vials
The immunogenicity of low dose VZV vaccine delivered into the outer layers of skin compared with the standard dose delivered conventionally is investigated.

A one-fifth injection dose of the chickenpox and herpes zoster vaccine delivered into the outer layers of skin resulted in the same or greater cellular immunostimulation of varicella-zoster virus (VZV) vs standard subcutaneous delivery, suggesting this intradermal injection at a greatly reduced dose may be equally efficacious to the established delivery and dose, according to study findings published in the Journal of Dermatological Science

Following primary childhood infection, VZV may remain latent throughout a lifetime, or due to aging and stress, reactivate after decades and produce herpes zoster (HZ), a result attenuated more than 50% by the VZV vaccine. But what about the other 49% of the population? Improved efficacy has been demonstrated in influenza vaccines delivered intradermally vs intramuscular or subcutaneous injections, the researchers acknowledged. They therefore sought to investigate immunogenicity of low dose VZV vaccine delivered into the outer layers of skin compared with the standard dose delivered conventionally.

To accomplish this, they conducted a prospective randomized study of 30 healthy participants (50 to 75 years of age) at the Nara Medical University School of Medicine from May 2015 to January 2019 who displayed superficial reddening less than 10 mm in diameter in the VZV skin test, which is believed to indicate a greater likelihood of contracting HZ. Among the participants, 13 (10 women; median age, 66 years) received the full dose (500 µL) VZV vaccine via standard delivery, and 17 (13 women; median age, 69 years) received low-dose (100 µL) through intradermal vaccine. 

VZV skin test reaction, proliferation of VZV-specific memory T cells, VZV-specific serum antibody levels, and peripheral blood cell cytokine production were used to assess VZV immunogenicity in both cohorts. Time between pre-injection and post-injection skin test was 43 days for all. Skin test reaction in both cohorts was nearly the same, the diameter of the erythema that the VZV skin test caused was significantly larger than caused pre-vaccination (subcutaneous: P =.0001; intradermal: P <.0001). The intradermal cohort showed significant increase in VZV-specific memory T cells, correlating with specific cytokines and cytotoxic molecules. The investigators reported no serious adverse events. 

Researchers concluded that the low-dose intradermal vaccine resulted in superior cellular immunity, while the standard dose and delivery more effectively raised antibodies. They continued, , “Intradermal injection with one-fifth dose VZV vaccine showed a similar or greater effect on VZV-specific cellular immunostimulation than conventional subcutaneous injection.” These findings suggest to the investigators that “one-fifth dose intradermal vaccination may have a comparable preventive effect to conventional subcutaneous injection.” Additional advantages of intradermal vaccine included no site reactions and a reduced cost, they wrote


Nakamura-Nishimura Y, Shinkuma S, Miyagawa F, et al. Immunogenicity of varicella-zoster virus vaccine by different routes of administration: Comparable vaccination efficacy of one-fifth dose intradermal vaccination to conventional subcutaneous vaccination. J Dermatol Sci. Published online April 4, 2022. doi:10.1016/j.jdermsci.2022.04.001