By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

SYNOPSIS: The adjuvanted recombinant herpes zoster vaccine is highly effective in practice, but it is vastly underused.

SOURCES: Sun Y, Kim E, Kong CL, et al. Effectiveness of the recombinant zoster vaccine in adults aged 50 and older in the United States: A claims-based cohort study. Clin Infect Dis 2021; Feb 13:ciab121. doi: 10.1093/cid/ciab121. [Online ahead of print].

Izurieta HS, Wu X, Forshee R, et al. Recombinant zoster vaccine (Shingrix) real-world effectiveness in the first two years post-licensure. Clin Infect Dis 2021; Feb 13:ciab125. doi: 10.1093/cid/ciab125. [Online ahead of print].

Sun and colleagues used a large administrative claims database to examine the real-world protective efficacy of Shingrix, an adjuvanted recombinant vaccine that was approved in the United States in 2017 for prevention of herpes zoster. Of the almost 5 million vaccine-eligible individuals in the database, only 173,745 (3.6%) received two doses of the vaccine, with the second dose received 30-210 days after the first dose. The median duration of follow-up after the second dose was 7.0 months. The incidence of herpes zoster in those who were vaccinated was 258.8 per 100,000 person-years, a significant reduction from the rate of 893.1 per 100,000 person-years in those who remained unvaccinated. The effectiveness was 86.8% in those 50-79 years of age and 80.3% in those  80 years of age. The overall effectiveness was 85.5% (95% confidence interval [CI], 84.6% to 88.7%) and was 84.8% in those who had received the live vaccine in the five years prior to receipt of the recombinant material. 

Using Medicare claims and enrollment databases, Izurieta and colleagues examined a cohort whose mean age was 74 years, approximately 10 years older than that examined by Sun et al. Of those who received the recombinant vaccine, 78% completed the second dose by six months and 86% completed it by 12 months. A delay in second dosing did not significantly affect outcomes. The overall adjusted vaccine efficacy was 70.1%, with little difference between those 65-79 years of age and those older. Those who received only a single vaccine dose had reduced protection: 56.9%. In those who had previously received the attenuated zoster vaccine (Zostavax), the efficacy was 63.0%, but this result presumably was artifactually diminished by residual effectiveness in the control group in this study. Receipt of both vaccine doses resulted in a protective efficacy of 76.0% against the development of post-herpetic neuralgia.  


Shingrix was approved for the prevention of herpes zoster in 2017 in adults 50 years of age. The vaccine requires two intramuscular doses given two to six months apart.

After its Food and Drug Administration approval, Shingrix supplanted Zostavax, which proved to be a less effective vaccine and, furthermore, as a live attenuated viral vaccine, was not recommended for use in immunocompromised patients. Although it requires two doses rather than one, the absence of replicative virus in this recombinant vaccine makes it potentially safer. On the other hand, the not insignificant incidence of non-severe adverse reactions (possibly related to the presence of an adjuvant) after receipt of Shingrix raised concern about whether, outside the cloak of a clinical trial, many patients might not return for a second dose. In fact, although the effectiveness of the vaccine was high in these studies, including when compared to Zostavax, effectiveness was lower than in the two clinical trials leading to the approval. The reasons for this are discussed further in an excellent comprehensive commentary by Harpaz.1

Perhaps the most startling result in these analyses was that only 3.6% of potential vaccine candidates in the United States had received the two vaccine doses. Given the efficacy and cost savings associated with its use, this is shameful. This also is a reflection of the inadequate support of public health measures, including vaccination, in the United States — an issue discussed by Harpaz and one which, if seized upon, could be affected favorably by lessons learned in the COVID-19 pandemic.1 In this regard, once again we have much to learn from our Canadian compatriots. Martins and colleagues reported that the introduction of a publicly funded herpes zoster immunization program in 2019 was associated with significant reductions in medically attended visits, emergency department visits, and hospitalization related to zoster and this was with the use of the less effective live virus vaccine.2 


  1. Harpaz R. The effectiveness of recombinant zoster vaccine: Observations in the wild. Clin Infect Dis 2021; Feb 13:ciab130. doi: 10.1093/cid/ciab130. [Online ahead of print].
  2. Martins D, McCormack D, Tadrous M, et al. Impact of a publicly funded herpes zoster immunization program on the burden of disease in Ontario, Canada: A population-based study. Clin Infect Dis 2021;72:279-284.