News Release 

Zika vaccine candidate shows promise in phase I trial

Embargoed news from Annals of Internal Medicine

American College of Physicians

Research News

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.

1. Zika vaccine candidate shows promise in phase I trial Abstract: https://www.acpjournals.org/doi/10.7326/M20-5306

Editorial: https://www.acpjournals.org/doi/10.7326/M21-0397

URL goes live when the embargo lifts

The Zika virus candidate, Ad26.ZIKV.001, a replication-incompetent human adenovirus serotype 26 (ad26) vector showed promising safety and immunogenicity in a phase I clinical trial. Researchers say the vaccine warrants further development should the need reemerge. The findings are published in Annals of Internal Medicine.

Zika virus (ZIKV) infection is transmitted via mosquito or sexually and may cause severe congenital disease after maternal-fetal transmission. The incidence of Zika virus has declined since the 2015-2016 outbreak, but geographic expansion of the Aedes aegypti mosquito to areas where population-level immunity is low poses a substantial risk for future epidemics. Currently, no vaccine is available.

Researchers from Janssen Vaccines and Prevention and Beth Israel Deaconess Medical Center randomly assigned 100 healthy participants to either a 1- or 2-dose regimen of Ad26.ZIKV.001 or placebo to assess the safety and immunogenicity of the Zika vaccine candidate. They found that 2 doses of Ad26.ZIKV.001 were safe, caused mild to moderate reactogenicity, and induced persistent neutralizing antibody responses. Transferred antibodies were found to be protective in a mouse Zika challenge model. Antibody responses up to 1 year after vaccination were observed in at least 80% of participants in both 2-dose (high and low) groups, indicating that a low dose would be sufficient. A single-dose vaccine had lower peak neutralizing antibody responses than the 2-dose strategies but nevertheless showed durable antibody titers at 1 year, and thus may be a useful tool in curbing future Zika epidemics.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. The corresponding authors, Nadine C. Salisch, PhD, and Dan H. Barouch, MD, PhD, can be reached at NSalisch@its.jnj.com.

2. Study suggests Zika blood screening policy may not be necessary or cost effective

Abstract: https://www.acpjournals.org/doi/10.7326/M20-6879

Editorial: https://www.acpjournals.org/doi/10.7326/M21-0397

URL goes live when the embargo lifts

A modeling study finds that universal screening of blood donations for Zika virus may not be necessary or cost effective, as the risk of serious adverse events from transfusion-transmitted Zika virus is exceedingly low. A resurgence of Zika that is even larger than the 2016-17 pandemic (which the author says is not likely) would be needed for the expected rate of serious adverse events from transfusion-transmitted Zika to exceed once-per-decade levels. The findings are published in Annals of Internal Medicine.

A 2019 simulation study found that screening the blood supply for Zika, which began in 2016, was not cost-effective in the 50 states during the first year. Despite these findings, the Blood Products Advisory Committee recommended continuing universal screening, which costs blood centers a collective $8 to $13 million each month. Discussions on this policy have been tabled due to the coronavirus pandemic, but the modeler suggests that this data could help to inform regulatory decisions.

A researcher from Stanford University used a simulation model to estimate the relationship between the rate of Zika-infectious donations and the rate of adverse outcomes due to transfusion-transmitted Zika in the 50 states without screening and estimate the 2018 cost-effectiveness of universal screening. At the rate of Zika-infectious donations from 2018, the report estimates that the rate of serious adverse events from transfusion-transmitted Zika would be below 1 congenital Zika syndrome case every 1,484 years and 1 Guillain-Barre syndrome case every 1,035 years. The report also estimates that universal screening with mini-pooled nucleic acid testing (the current standard) costs $5.1 billion per quality-adjusted life year gained (98% Credible Interval $0.77 - $16 billion). According to the study author, collaboration between modelers and policy-makers could enhance the policy relevance of modeling studies.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. The corresponding author, W. Alton Russell, can be reached directly at altonr@stanford.edu.

3. Immune checkpoint inhibitors may not cause serious flare ups in patients with preexisting autoimmune diseases

Abstract: https://www.acpjournals.org/doi/10.7326/M20-3419

URL goes live when the embargo lifts

Immune checkpoint inhibitors (ICI) may not trigger serious flare ups in patients with melanoma and preexisting autoimmune diseases. However, adverse events may be more likely in patients with inflammatory bowel disease (IBD). Findings from a nationwide cohort study are published in Annals of Internal Medicine.

ICI can increase survival and lead to long-lasting responses in patients with melanoma. But because ICIs have been shown to cause immune-related adverse events mimicking immunologic diseases, patients with preexisting autoimmune disease have been excluded from clinical trials.

Researchers from Leiden University Medical Center, the Netherlands studied over 4,000 patients enrolled in the Dutch Melanoma Treatment Registry to test the hypothesis that serious immune-related adverse events would occur more frequently in patients treated with ICI with advanced melanoma and autoimmune diseases than in patients without autoimmune diseases. They also compared baseline characteristics, treatment choices, response, and survival after ICI.

The researchers found that tumor response to ICI treatment and incidence of immune-related adverse events of grade 3 or higher were similar in patients with and without preexisting autoimmune disease of rheumatologic or endocrine origin in daily clinical practice. For patients with IBD, the researchers noted higher incidence of severe colitis and early discontinuation of treatment due to toxicity. These findings suggest that physicians do not need to withhold ICI in patients with the most common autoimmune diseases. However, close monitoring in patients with IBD is advised.

Media contacts: For an embargoed PDF, please contact Angela Collom at acollom@acponline.org. The corresponding author, Ellen Kapiteijn, MD, PhD, can be reached directly at h.w.kapiteijn@lumc.nl.

Also in this issue:

Perioperative Management of Patients on Glucocorticoids
Caputo
Consult Guys
https://www.acpjournals.org/doi/10.7326/W20-0018

Trends in Endocarditis Associated with Injection of Illicit Drugs
Centor
Annals On Call
https://www.acpjournals.org/doi/10.7326/A20-0007

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