NIH trials seek answers on monkeypox vaccine delivery, antiviral
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The NIH this month began enrolling participants in a clinical trial to investigate the efficacy of fractional doses of monkeypox vaccine, and another trial evaluating the antiviral tecovirimat in adults and children with monkeypox.
“Experience from prior studies and the thousands of doses that have been administered in the past few months in response to the outbreak indicate that the vaccine has a good safety profile and produces antibodies that should neutralize the monkeypox virus to prevent infection,” David Diemert, MD, professor of medicine and of microbiology, immunology and tropical medicine at George Washington University and head of one of the eight sites for the NIH-sponsored vaccine trial, told Healio in an email.
“It is often the case that the antibody response to a vaccine can ‘max out’ so that giving higher doses doesn’t give higher antibody responses — that is, a plateau is reached. Therefore, giving smaller doses may not in fact lead to lower antibody responses if the dose is still on the plateau part of the dose-response curve,” Diemert said.
The trials, according to National Institute of Allergy and Infectious Diseases Director Anthony S. Fauci, MD, will test three methods of inoculation: the already licensed standard two-dose subcutaneous regimen; an intradermal regimen using one-fifth the standard dose; and an intradermal regimen using one-tenth the standard dose. The one-fifth-sized dosing regimen was authorized by the FDA in August, and thousands of vaccinations have since been distributed.
“We’re going to determine whether the peak responses induced in the recipients intradermally are at least as good as the responses introduced with regard to the licensed subcutaneous regimen,” in addition to collecting data on tolerability and relative safety of the regimens, Fauci said last week during a briefing by the White House National Monkeypox Response team.
The fractional dose concept is based on data from a 2015 clinical study evaluating the vaccine when delivered intradermally, rather than subcutaneously. Participants in the study receiving the intradermal vaccination were given one-fifth the dose of those receiving it subcutaneously.
Data from that study showed additional side effects at the injection site among intradermal recipients — redness, firmness, itchiness and swelling — but a similar immune response in both sets of participants, according to the FDA.
“Broadly, I would say we don’t have strong real-world efficacy data yet on how well the Jynneos vaccine works, so other measures like developing rapid tests and understanding spillover into non-[men who have sex with men] communities will be important until we know how durable the vaccine response is,” Abraar Karan, MD, MPHDTM&H, an infectious disease fellow and post-doctoral researcher in the division of infectious diseases at Stanford University, told Healio in an email.
As of Sept. 14, the CDC reported a total 24,203 cases of monkeypox and one death in the United States, and 63,117 cases globally.
Robert Fenton, the White House’s national monkeypox response coordinator, reported that new cases have dropped 50% since a peak in August. Federal officials pegged some of this decline to successes in its large event outreach program, which made up to 50,000 doses available for large LGBTQ events, leading to the announcement of a small-event version of the program last week.
A preprint study uploaded to medRxiv on Sept. 1 suggested that fractional doses may not provide enough protection to make the effort worth it. That study, however, has not been peer reviewed and used data from several studies. Additionally, individual labs in the studies developed their own method for measuring neutralizing antibodies, “which can be tricky,” Diemert said.
“For this reason, the study we’re currently doing is using the more accepted neutralizing antibody test against the vaccinia — similar to cowpox — virus that has been used for decades to measure the immune response to smallpox vaccines as the primary antibody endpoint,” Diemert said.
The NIH said the trial will take 15 months to complete, although initial data are expected to be available early next year.
The NIH also began enrolling adults and children with monkeypox infection in a phase 3 clinical trial to evaluate the antiviral tecovirimat, which is being led by the AIDS Clinical Trials Group. The vaccine and antiviral trials are both sponsored by the NIAID.
The NIH said the trial of tecovirimat — which is approved in the U.S. for smallpox and being used under expanded access for monkeypox — will gather data to determine if participants in the treatment group heal more quickly compared with those taking placebo, and what impact the antiviral has on pain scores, rates of progression to severe disease and clearance of monkeypox virus, in addition to its safety. It also will provide data on optimal dosing and safety in children and people who are pregnant, the NIH said.
Fauci, at the briefing last week, also said that data from the NIH studies on the vaccine and tecovirimat will be used to develop other measures for future studies, in addition to gathering efficacy data.
References:
- CDC. Monkeypox: 2022 outbreak cases and data. https://www.cdc.gov/poxvirus/monkeypox/response/2022/index.html. Accessed Sept. 21, 2022.
- Clinical trial evaluating monkeypox vaccine begins. https://www.nih.gov/news-events/news-releases/clinical-trial-evaluating-monkeypox-vaccine-begins. Published Sept. 8, 2022. Accessed Sept. 21, 2022.
- Fact sheet: U.S. Department of Health and Human Services response to the monkeypox outbreak. https://www.hhs.gov/about/news/2022/07/21/fact-sheet-us-department-of-health-and-human-services-response-to-the-monkeypox-outbreak.html. Published July 21, 2022. Accessed Sept. 21, 2022.
- Monkeypox update: FDA authorizes emergency use of Jynneos vaccine to increase vaccine supply. https://www.fda.gov/news-events/press-announcements/monkeypox-update-fda-authorizes-emergency-use-jynneos-vaccine-increase-vaccine-supply. Published Aug. 9, 2022. Accessed Sept. 21, 2022.
- U.S. clinical trial evaluating antiviral for monkeypox begins. https://www.nih.gov/news-events/news-releases/us-clinical-trial-evaluating-antiviral-monkeypox-begins. Published Sept. 9, 2022. Accessed Sept. 21, 2022.
- Zaeck LM, et al. medRxiv. 2022;doi:10.1101/2022.08.31.22279414
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