NIH trial to test safety, efficacy of monoclonal antibody for dengue
Key takeaways:
- A phase 2 human challenge trial will measure time to recovery from dengue and determine effective doses of the monoclonal antibody.
- There are currently no therapeutics for dengue virus infection.
The NIH announced that it is launching a phase 2 human challenge trial of AV-1, an investigational monoclonal antibody to ease dengue virus symptoms when given before and after infection.
“When caring for a patient who is critically ill with dengue, health care providers have few options other than providing supportive care,” National Institute of Allergy and Infectious Diseases Director Jeanne Marrazzo, MD, MPH, said in a press release. “We must find safe and effective therapeutics to provide much-needed relief to people suffering from dengue.”
Dengue virus, which has four serotypes and is spread through the bite of Aedes mosquitoes, is the most common mosquito-borne disease worldwide.
Although infection with one of the four dengue serotypes confers lifelong protection against that serotype, people can still be infected by the other three. In fact, a prior infection caused by one serotype raises a person’s risk for severe dengue disease if they are infected with another serotype, which made developing a vaccine difficult.
Dengue is most commonly found in tropical and subtropical parts of the world, according to the NIH. Although most cases in the United States are related to travel, the NIH noted that in 2024, local U.S. transmission was reported in Arizona, California, Florida, Hawaii and Texas. The virus is endemic in Puerto Rico. In July, the CDC issued a warning about a surge in dengue in the U.S.
Across the Americas, there were more than 13 million dengue cases in 2024, with 22,684 severe cases and 8.186 deaths, according to the Pan American Health Organization (PAHO).
In 2025, PAHO reported 239,659 dengue cases as of Feb. 10, with 263 severe cases and 23 deaths in the Americas. Although cases have been reported across 23 countries and territories so far this year, the vast majority — 87% — have been reported in Brazil.
NIH researchers plan to enroll 84 adult volunteers at two sites in the trial, splitting them randomly into two groups: One group will receive AV-1 a day before being challenged with a mild strain of serotype 3 dengue, while the other group will be treated with AV-1 4 days after being challenged with the mild strain of the virus.
Each of the groups will also be split into three groups, with 12 receiving AV-1 doses of either 100 mg, 300 mg or 900 mg, delivered intravenously, and two given a placebo. Researchers will then follow-up with participants at regular visits for at least 155 days, according to the NIH.
References:
- An evaluation of repeated oral doses of JNJ-64281802 against DENV-3 challenge. https://clinicaltrials.gov/study/NCT05048875. Updated Nov. 13, 2023. Accessed Feb. 13, 2025.
- CDC. Dengue: Current dengue outbreak. https://www.cdc.gov/dengue/outbreaks/2024/index.html. Updated Nov. 24, 2024. Accessed Feb. 13, 2025.
- NIH-funded clinical trial will evaluate new dengue therapeutic. https://www.nih.gov/news-events/news-releases/nih-funded-clinical-trial-will-evaluate-new-dengue-therapeutic. Published Feb. 11, 2025. Accessed Feb. 13, 2025.
- PAHO warns of increased risk of dengue outbreaks due to circulation of DENV-3 in the Americas. https://www.paho.org/en/news/10-2-2025-paho-warns-increased-risk-dengue-outbreaks-due-circulation-denv-3-americas. Published Feb. 10, 2025. Accessed Feb. 13, 2025.
Perspective
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Recent years have seen an explosion of dengue infections in South America, South and Southeast Asia, as well as increased autochthonous transmission in the U.S. and Western Europe. Although there has been some progress in control measures (eg, Wolbachia-infected mosquitoes) and vaccination, albeit incomplete in terms of protection against all four dengue serotypes, we currently have no antiviral drugs active against dengue virus. Given the potential acute and medium-term morbidity and mortality associated with dengue infection, there is an urgent need for therapeutic and prophylactic agents.
Although the monoclonal antibody being tested in human studies is an exciting development, the design of the study will provide initial evidence on its efficacy and safety but will need to be followed by pragmatic studies testing its effectiveness against different serotypes and at different time points after the initial onset of symptoms.
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