Dynavax’s Z-1018 Shingles Vaccine Candidate Shows Promising Immune Response and Safety in Early Trial

In part 1 of the randomized, observer-blinded, and active-controlled phase 1/2 clinical trial, Z-1018 (Dynavax Technologies Corporation), a novel shingles vaccine candidate, demonstrated positive topline results of antibody and CD4⁺ T cell vaccine responses, such as those found in the comparator arm receiving the zoster vaccine recombinant, adjuvanted (Shingrix; GSK).¹

Man with shingles disease, skin infected with Herpes zoster, virus, Healthcare and medical - Image credit: Suriyawut | stock.adobe.com

"These positive data mark an important inflection point for our novel shingles vaccine program as we strive to develop a product with a potential best-in-class profile with the aim to disrupt the multibillion-dollar shingles vaccine market, which is currently dominated by one product," Ryan Spencer, chief executive officer of Dynavax, said in a news release.¹

Understanding the Development of Shingles

Shingles, also known as herpes zoster, is a viral infection that causes a painful rash on any area of the body, presenting as a single stripe of blisters that commonly wraps around the left side or the right side of the torso. The infection is caused by a reactivation of the varicella-zoster virus that remains dormant in the body after experiencing chickenpox. The virus impacts 1 in 3 people in their lifetime and permanently stays in the body.^1,2

While shingles is not life-threatening, it causes significant pain and other symptoms, such as burning or tingling, sensitivity to touch, a red rash, fluid-filled blisters that break open and crust over, and itching. However, some individuals could experience fever, headache, sensitivity to light, and fatigue.²

Vaccines for shingles lower an individual’s risk of reactivating the varicella-zoster virus, and early treatment often shortens the duration of a shingles infection and lessens the risk of complications, including postherpetic neuralgia.²

“Shingles is a painful disease driven by cellular immune decline with age,” Robert Janssen, MD, chief medical officer of Dynavax, said in the news release. “A vaccine that provides a strong immune response alongside favorable tolerability, compared to the current standard of care, could provide an important new option for protection against this debilitating disease."¹

Z-1018 Prevention for Shingles Injection

As an investigational nonlive, recombinant subunit vaccine, Z-1018 is in development for the prevention of shingles among adults aged 50 years and older. The vaccine combines an antigen, glycoprotein E, with CpG 1018—a proprietary adjuvant system from Dynavax—and alum. This combination is designed to help boost the immune response, aiming to overcome the natural age-related decline in immunity that makes it difficult to protect older adults from shingles.¹

To assess the safety, tolerability, and immunogenicity of the vaccine, researchers compared Z-1018 with the zoster vaccine recombinant, adjuvanted, which received FDA approval in 2017 for preventing shingles in adults aged 50 years and older and was later expanded in July 2021 to include adults aged 18 years and older who are at increased risk of shingles. The study included healthy adult patients aged 50 to 69 years.^1,3

The key objective of part 1 of the phase 1/2 trial was to evaluate 3 different gE antigen dose levels—50 mcg, 100 mcg, and 200 mcg—in combination with 2 adjuvant formulations, either CpG 1018 alone or with alum, and to assess 2 different dosing schedules, an 8-week and a 12-week regimen. The main safety end point was solicited local and systemic post-injection reactions, which were measured for 7 days after each dose. Immunogenicity was measured by vaccine response rates (VRRs) for both anti-gE IgG antibodies and gE-specific CD4+ T-cells 4 weeks after the second injection. The study authors noted that VRRs were defined as a greater than 4-fold increase in anti-gE IgG concentration and a greater than 2-fold increase in CD4+ T-cell frequency from baseline, with a composite VRR for those meeting both criteria.¹

The results demonstrated that at 1 month after the second vaccine dose, Z-1018 had similar antibody and CD4+ T cell vaccine responses to those in the zoster vaccine recombinant adjuvanted group.¹

"We are very encouraged by the magnitude and consistency of the immune responses observed, particularly the robust CD4⁺ T cell activity for Z-1018 compared to Shingrix," Janssen said in the news release.¹

For the dose chosen to advance to part 2 of the trial, Z-1018 achieved a 100% humoral vaccine response rate compared with the zoster vaccine recombinant at 96.9%. Its cellular immune response rate was 89.7% compared with 93.5% in the comparator groups, resulting in a composite vaccine response rate of 89.7% for Z-1018 versus 90.3% for the zoster vaccine recombinant.¹

Further results found that Z-1018 also demonstrated a favorable safety profile, with low rates of local and systemic postinjection reactions. Specifically, only 12.5% of Z-1018 recipients reported grade 2 or 3 local reactions, and 27.5% reported systemic reactions, which was significantly lower than the zoster vaccine recombinant, which had rates of 52.6% and 63.2%, respectively. Additionally, the study authors noted that the ongoing trial has not identified any safety concerns.¹

"We met our goal for this study, as the results show immune responses comparable to [zoster vaccine recombinant], along with a favorable tolerability profile, and provide the basis for selecting the dose and regimen to advance into further development. Based on these findings, plans are underway to initiate part 2 of the phase 1/2 trial in the 70 and older population, an opportunity to further de-risk this program ahead of Phase 3 development,” Spencer said in the news release.¹

REFERENCES

1. Dynavax Announces Positive Topline Phase 1/2 Results Supporting Potential Best-in-Class Shingles Vaccine Profile. Dynavax. News release. August 21, 2025. Accessed August 26, 2025. https://investors.dynavax.com/news-releases/news-release-details/dynavax-announces-positive-topline-phase-12-results-supporting

2. Shingles. Mayo Clinic. News release. August 20, 2022. Accessed August 26, 2025. https://www.mayoclinic.org/diseases-conditions/shingles/symptoms-causes/syc-20353054

3. U.S. Food and Drug Administration. Updated July 17, 2025. SHINGRIX. Accessed August 26, 2025. https://www.fda.gov/vaccines-blood-biologics/vaccines/shingrix