Sustained Efficacy Over 11 Years Without Waning: Breakthrough and Challenges of the Recombinant Zoster Vaccine

Herpes zoster is caused by varicella- Painful rash caused by the varicella-zoster virus (VZV). Statistics show that about one-third of the global population will suffer from shingles in their lifetime, of which approximately 10%-30% of patients will develop postherpetic neuralgia (PHN). The pain can last for months or even years, severely affecting the quality of life.

Published on May 9 in The Lancet Sub-JournaleClinicalMedicineThe latest research shows that GSK's adjuvanted recombinant zoster vaccine (RZV) still provides up to 79.8% protection efficacy within 11 years after vaccination, with significant preventive effects on complications!

RZV "Ultra-long Standby" 11-year Protective Efficacy

This study isThe long-term follow-up extension of the two Phase III clinical trials, ZOE-50 and ZOE-70, included a total of 7,273 participants who received RZV, with follow-up lasting up to 11 years. The main findings of the study include:

Overall Protective Efficacy:InIn individuals aged ≥50 years, the efficacy of RZV against herpes zoster is 79.8% (95% CI: 73.7, 84.6); in those aged ≥70 years, it is 73.2%.

Long-term protection:After vaccinationFrom 1 month to the 11th year, the overall protective efficacy was 87.7%, and it remained as high as 82% in the 11th year. The protective efficacy against postherpetic neuralgia (PHN) was 87.5%, and the protective efficacy against other complications (such as disseminated infections, ocular or neurological diseases) was 91.7%.

Long-lasting Immunogenicity:Anti-The gE antibody level remained 5.8 times higher than the pre-vaccination level 12 years after vaccination, and the frequency of gE-specific CD4+ T cells was still significantly higher than the baseline level 12 years after vaccination.

Good safety profile:The ZOE-LTFU study showed that RZV did not present any vaccine-related serious adverse events (SAEs) during long-term follow-up, with common adverse reactions being only transient injection site pain or fever, indicating controllable safety.

WhyCan RZV become a global blockbuster later on?

The heavy disease burden of herpes zoster also indicates a huge market potential.In 2006, the FDA approved MSD's quadrivalent HPV vaccine and also approved another blockbuster vaccine that year — the attenuated zoster vaccine (ZVL, trade name: Zostavax).

Although it filled the gap in herpes zoster prevention at the time, its high price came with a notable decline in protective efficacy: dropping to 51.3% after 5 years. A real-world study published in the BMJ last year showed that the protective efficacy of the ZVL vaccine was only 15% ten years after vaccination. Additionally, the attenuated process further limits the application of this vaccine in immunocompromised individuals, who are also a high-risk group for herpes zoster.

In 2017, the FDA approved another adjuvanted recombinant zoster vaccine (RZV) for marketing in the U.S. And in less than a year, RZV was included in the first list of clinically urgent overseas new drugs needed in China.

Another product that broke conventions even more and entered China in the same year was MSD’s 9-valent HPV vaccine, which completed the entire process from application to approval for marketing in less than 10 days. This also clearly demonstrates the urgency of China's demand for the shingles vaccine and the market expectations for this vaccine.

ThereafterIn 2020, less than three years after its U.S. launch, this vaccine was approved for use in China, making it the fifth country to market after the United States, Canada, Germany, and Japan. The priority and importance GSK places on access to the Chinese market is evident. According to GSK's financial report, in 2022, RZV's global sales exceeded $3 billion, becoming the second-largest vaccine product after MSD's Gardasil/Gardasil9.

It was not until 2023 that the attenuated shingles vaccine developed in China began to be approved for marketing, applicable to people aged ≥40. Although the protective effect is slightly discounted, the overall price is more affordable.

Why Does the Shingles Vaccine "Fizzle Out" in China?

Despite the excellent data on vaccine efficacy and high hopes from a group of investors and ZF Bio,RZV has consistently struggled to gain traction in China, lagging far behind MSD's nine-valent HPV vaccine.

This is because the active health consumption power of the target elderly population is too weak, and China's aging has come too fast—unlike developed countries, China is a typical case of "getting old before getting rich."

Unlike the economic transformation and change in consumption habits over hundreds of years in foreign countries, China has leapfrogged from a poor agricultural society to a modern information-based society within just a few decades. The vast majorityElderly people over 60 were born in an era of turmoil and extreme material scarcity, and compared to the hardships of life, the pain caused by herpes zoster may not even be worth mentioning.

Compared to the strong health consumption power of young women regarding HPV vaccines (not just strong consumption power for HPV vaccines) and their advanced consumption concepts, the shingles vaccine can only wait anxiously.

A 2023 study showed that 42.67% of respondents were willing to receive the shingles vaccine, while 57% refused or were hesitant. The results of another in-depth qualitative interview study were even more discouraging – only 16 out of 59 participants (27.1%) expressed willingness to get the shingles vaccine.

Other factors are the first barrier to vaccination, while price is the last portcullis preventing vaccination!

A 2020 study in Shanghai showed that among participants aged 50-69, 16.57% expressed willingness to get vaccinated themselves, while 13.88% and 8.49% were willing to vaccinate their spouses and parents, respectively. However, if the vaccine were covered by insurance, these figures would increase to 72.25%, 62.50%, and 29.96%, respectively. A 2022 survey across multiple cities in China revealed that lack of awareness about shingles and high costs were the main barriers.

As the top-ranking province or city in China's economy, if people in Shanghai consider the shingles vaccine expensive, then the initial positioning or pricing of this vaccine may have significant issues, and other obstructing factors will become negligible by comparison.

A recent survey research at the national level in China can also serve as supporting evidence:Among respondents aged over 40, 0.79% received the herpes zoster vaccine, with a higher proportion receiving the live attenuated herpes zoster vaccine compared to the recombinant herpes zoster vaccine (35.96% vs. 29.82%, ~¥1400 vs. ¥3200).

Core Competitiveness: Long-lasting Effectiveness, Effective Recommendations, and Additional Benefits

The total cost of the recombinant shingles vaccine is approximately 3200 yuan, while the total cost of the attenuated shingles vaccine is about 1400 yuan. Therefore, the data on long-lasting protective efficacy is extremely critical evidence for a preventive vaccine priced at approximately 1600 yuan per dose (two doses in total). No one wants to spend 3200 yuan only to miss the effective protection period before the prevention of the disease kicks in!

The current institutional design of integrating medical prevention and adult vaccine prescriptions may also be an important way to counteract vaccine hesitancy: a foreign study shows that the willingness to get vaccinated without healthcare worker recommendations is approximately49.4%, while the willingness to vaccinate can increase to 75.2% if recommended by healthcare professionals.

For manufacturing companies, adding extra benefits to this vaccine could be a crucial way to offset its high price. In recent years, studies suggesting a potential link between the shingles vaccine and a lower incidence of Alzheimer's disease in the elderly have begun to emerge in large numbers.

This year, GSK's executives have ambitiously announced plans to launch a clinical study involving millions of people in an effort to establish a causal relationship between it and a lower incidence of Alzheimer's disease.

Who Should Get Vaccinated? When to Get Vaccinated?

Healthy adults aged ≥40 years, regardless of whether they have had chickenpox or shingles, are recommended to be vaccinated. Patients with diabetes, chronic kidney disease, or cardiovascular disease are advised to be vaccinated, and immunocompromised individuals (such as cancer patients) can receive the RZV vaccine.

In addition, there are two common misconceptions about the herpes zoster vaccine: one is"Patients who have had shingles do not need to be vaccinated." In fact, the virus can be reactivated multiple times, and vaccination can still prevent recurrence. Secondly, "the vaccine is too expensive and not worth getting vaccinated." Compared with treatment costs (e.g., annual treatment costs for PHN exceed ten thousand yuan), vaccination is more cost-effective.

References:

https://doi.org/10. 1016/j.eclinm.2025. 103241

BMJ 2023;383:e076321.

BMJ Open. 2023 Dec 7;13(12):e079115.

Glob Health Res Policy. 2025 Apr 18;10(1):19.

Hum Vaccin Immunother. 2021 Nov 2;17(11):4163-4170.

Vaccine. 2025 Apr 19;56:127122. 

JMIR Public Health Surveill. 2023 Mar 9;9:e43893.

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