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This is a plain English summary of an original research article. The views expressed are those of the author(s) and reviewer(s) at the time of publication.

A non-live vaccine against herpes zoster provides good, though partial protection for adults undergoing autologous (using the patient’s own) stem cell transplant for treatment of blood cancers. These people cannot use the usual live vaccine, because of their suppressed immune system.

An industry-funded trial of the vaccine involved 1,846 patients from 28 countries, including the UK. Two doses of the vaccine resulted in a 68% reduction in cases of shingles over 21 months of follow-up. Shingles is a frequent and painful occurrence after stem cell transplant. This is a similar effect to another non-live vaccine that is given in four doses, but less than the 91% reduction expected for these vaccines given to people who are not immunosuppressed.

The vaccine was administered 50 to 70 days after transplantation, and the second dose two months after the first. The main side effects were injection site reactions, primarily pain, but these passed within days.

Why was this study needed?

People with lowered immune systems are at risk of developing shingles, which is caused by the same herpes zoster virus that causes chickenpox. People having autologous stem cell transplants as part of treatment for blood or bone marrow cancer such as myeloma are at an increased risk of shingles because of their compromised immune systems.

However, they cannot be given the usual herpes zoster vaccine offered to older people to prevent shingles, because that contains live virus. Doctors have now tested at least two forms of inactivated herpes zoster vaccine for use in people with lowered immune systems due to stem cell transplant.

The aim is to find a vaccine that can be safely administered to this population, which cuts the risk of shingles and complications such as post-herpetic neuralgia.

What did this study do?

This randomised controlled trial compared recombinant zoster vaccine with placebo in 1,846 adults from 167 centres, including the UK. All had undergone recent autologous haemopoietic stem cell transplantation for blood cancers, most commonly multiple myeloma (53%).

The first dose was administered 50 to 70 days after transplantation and the second dose one to two months after the first. Vaccines were injected into the upper arm. Participants were followed for up to two years (median follow up 21 months, measured from the second dose).

The researchers recorded adverse events, cases of herpes zoster and pain related to herpes zoster.

What did it find?

  • Most participants received both doses of vaccine (94.7% in the vaccine group and 93.3% in the placebo group), with only 9 or 10 patients in each group not receiving the first vaccine.
  • Fewer people, 5.6% (49/870) who received the vaccine had at least one episode of shingles compared with those who received the placebo injection, 15.8% (135/851). This translated to an incidence of 30 per 1,000 person-years for vaccinated people and 94 per 1,000 person-years for unvaccinated people.
  • The vaccine was 68.2% effective (incident rate ratio [IRR] 0.32, 95% confidence interval [CI] 0.22 to 0.44) after two doses.
  • Injection site reactions including pain were much more common in the vaccine group (83.9%) than the placebo group (9.3%), but there was no difference in serious adverse events (28.5% vaccine group compared to 26.1% placebo group) which were mainly relapses of malignancy and unrelated to the vaccination.

What does current guidance say on this issue?

The American Society for Blood and Marrow Transplantation published guidelines in 2009 on reducing infection risk among hematopoietic cell transplantation recipients.

The guidelines stated that the live herpes zoster vaccine available at the time was contraindicated. They recommend instead 12-month prophylactic use of the antiviral agent acyclovir, as well as general infection control measures.

What are the implications?

The risk of shingles is about 10% per year in adults after autologous stem cell transplant. These results indicate that two doses of deactivated herpes zoster vaccine could be a safe and effective way to reduce that risk by about two thirds.

This effect is similar to another, heat-treated, non-live vaccine. Either vaccine could reduce the pain and need for medical treatment associated with shingles, and long-lasting complications such as post-herpetic neuralgia. We don’t yet know if people need to continue taking acyclovir as well.

Citation and Funding

Bastidas A, de la Serna J, El Idrissi M, et al. Effect of recombinant zoster vaccine on incidence of herpes zoster after autologous stem cell transplantation: a randomized clinical trial. JAMA. 2019;322(2):123–33.

This study was funded by GlaxoSmithKline Biologicals SA.



American Society for Blood and Marrow Transplantation, Tomblyn M, Chiller T, Einsele H et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15: 1143-238.

Winston DJ, Mullane KM, Cornely OA et al. Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2018;391:2116–27.

Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre


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