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U.S. health regulators last month authorized injecting the shot intradermally in adults, meaning between layers of the skin rather than below the skin, in an effort to stretch out low vaccine supplies.
This alternative intradermal dosing regime will allow health care providers to administer up to five times the number of vaccine doses per vial of shot.
The NIH trial will enroll 200 people between 18 and 50 years of age, who have not been previously vaccinated across eight U.S. research sites.
Nearly 20,000 cases of monkeypox have been reported in the United States since May when a large global outbreak began in countries where the virus is not endemic, according to government data.
