Two-dose recombinant shingles vaccine is effective even accounting for prior receipt of live shingles vaccine

Embargoed for release until 5:00 p.m. ET on Monday 13 October 2025   

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Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information. This information is under strict embargo and by taking it into possession, media representatives are committing to the terms of the embargo not only on their own behalf, but also on behalf of the organization they represent.   
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1. Two-dose recombinant shingles vaccine is effective even accounting for prior receipt of live shingles vaccine 

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-24-02409

URL goes live when the embargo lifts             

A target trial emulation was conducted to assess the effectiveness of recombinant zoster vaccine (RZV) accounting for prior receipt of live zoster vaccine (ZVL) and immunocompetence. The study found that RZV achieved over 50% vaccine effectiveness (VE) against any herpes zoster (HZ), or shingles, outcome in both older and immunocompromised adults. The results suggest individuals vaccinated with ZVL should be revaccinated with two doses of RZV. The study is published in Annals of Internal Medicine.

Researchers from University of North Carolina, Chapel Hill conducted two analyses of a random sample of adults aged 65 years or older enrolled in Medicare Parts A, B, and D with fee-for-service coverage between 2007 and 2019. Participants had to have six months of continuous coverage before trial enrollment, no claims for HZ since 2007, and no prior RZV vaccination. The first analysis measured the effectiveness of one or more RZV doses versus none, and the second analysis measured the effectiveness of two RZV doses versus one dose. Among 3,456,555 unique individuals evaluated across 12 emulated trials in analysis 1, the 1-year VE of at least 1 RZV dose as 56.1% (95% CI, 53.1% to 59.0%) against any HZ outcome. VE was similar among individuals aged 65 to 80 years and among immunocompromised and immunocompetent individuals. VE was 51.8% (CI, 44.7% to 57.9%) among individuals who had previously received ZVL vaccination compared with 57.7% (CI, 54.2% to 60.9%) among those who had not. In analysis 2, 146,296 individuals were evaluated across 10 emulated trials to determine the effectiveness of two doses of RZV versus one. The analysis found that receipt of two RZV doses yielded a relative VE of 67.9% (CI, 64.2% to 71.3%) against any HZ outcome compared with one dose. Additionally, the analysis found that the second dose is similarly effective whether it is administered within the CDC-recommended window or within an extended window after the first dose. These findings can be used to inform the CDC’s recommendations on RZV in immunocompromised populations and populations who previously received ZVL.

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact corresponding author Nadja A. Vielot, PhD please email Reid Johnson at reid_johnson@med.unc.edu. 

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2. Experts debate recommendations for breast cancer screening for a 39-year-old woman

This ‘Beyond the Guidelines’ feature is based on a discussion held at the annual American College of Physicians Internal Medicine Meeting held on 5 April 2025.

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-03548

URL goes live when the embargo lifts             

In a new Annals “Beyond the Guidelines” feature, two physicians debate the 2024 U.S. Preventative Services Task Force recommendations of biennial screening mammography for women aged 40 to 74 years in the context of Ms. R, a 39-year-old woman. Currently, an American woman has a 1 in 47 chance of developing invasive breast cancer from birth to 49 years of age, and 1 in 8 from birth to death. In 2016, the USPSTF recommended screening for women starting at age 50, but after a recent evidence review and commissioned study, they updated their statement in 2024 to recommend biennial screening starting at age 40. As such, asking “When would you screen this 39-year-old woman for breast cancer?” is an important clinical question.   

The authors reviewed the case of Ms. R, a 39-year-old-woman with illness-induced asthma, gastroesophageal reflux disease, and a borderline cholesterol level. She has had no prior breast masses or biopsies and no family history of breast or ovarian cancer. She has a fear of being diagnosed with a chronic health issue and expressed interest in starting breast cancer screening at 40, however, she also has anxiety over receiving false-positive or false-negative results.  

The first discussant, John B. Wong, MD, is a Vice-Chair of the U.S. Preventive Services Task Force, a member of the Division of General Internal Medicine at Tufts Medical Center, and a Professor of Medicine at Tufts University School of Medicine, Boston, Massachusetts. Dr. Wong notes that although Ms. R is at average risk without any signs of breast cancer, she is still at higher risk than prior eras of average-risk women in their 40s given epidemiologic trends for U.S. women in the 40s. He cites data that showed breast cancer incidence increased by 2% per year from 2015 to 2019 in 40- to 49- year-old-women. Dr. Wong also emphasizes how mammography can detect breast cancer at earlier and more treatable stages. In line with the USPSTF recommendation, he suggests that Mr. R begin mammographic screening every other year at 40 to reduce her chances of breast cancer.  

The second discussant, Mette Kalager, MD, PhD, is a Professor and the Head of the Clinical Effectiveness Research Group in the Department of Transplantation Medicine at Oslo University Hospital and Department of Health and Society, Medical Faculty, University of Oslo, Oslo, Norway. Dr. Kalager finds faults in the USPSTF recommendation, citing that the decision is based on low-quality modeling data. She says that the frequency of unnecessary follow-up imaging and biopsies, resultant anxiety, false-positives, false-negatives, and interval cancers are important drawbacks of routine mammography. Dr. Kalager does not recommend routine mammography for any woman at average risk, including Ms. R, and says that improvements in breast cancer therapy over several decades improve breast cancer outcomes and therefore lower the potential benefits of early detection through screening.  

All “Beyond the Guidelines” features are based on selected clinical conferences at Beth Israel Deaconess Medical Center (BIDMC) and include multimedia components published in the Annals of Internal Medicine.  

Media contacts: For an embargoed PDF, please contact Gabby Macrina at gmacrina@acponline.org. To contact series coordinator Kendra McKinnon please email Kmckinn1@bidmc.harvard.edu. 

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Also new this issue:

Chronic Coronary Artery Disease

Michelle M. Kittleson, MD, PhD

In the Clinic

Abstract: https://www.acpjournals.org/doi/10.7326/ANNALS-25-03512