NATIONAL HARBOR, Md. — Work towards a vaccine against hookworm continued, as a vaccine consisting of dermal application of attenuated hookworm larvae was mostly safe and well-tolerated in healthy volunteers, a researcher said here.
In this human challenge study, patients who received the vaccine developed a sensitized phenotype, with significantly greater areas of swelling after subsequent exposure to hookworm larvae as part of the trial, reported Paul Chapman, MD, of Queensland Institute of Medical Research-Berghofer in Herston, Australia at a presentation at the annual meeting of the American Society of Tropical Medicine & Hygiene.
Hookworm infection is primarily observed in the developing world. It was once widespread in the southern region U.S., according to CDC data, but is now mostly considered eliminated from the country. However, a 2017 report found that more than a third of individuals in rural Alabama had evidence of hookworm in their stool, and in July 2018, there were reports of a teenager contracting the parasite from visiting a beach in Florida.
In this small phase 1b trial, Chapman and colleagues randomized 15 healthy, hookworm-naive volunteers in Australia 2:1 to receive either two doses of attenuated 50 Necator americanus larvae or an unusual placebo — Tabasco sauce. Both were applied to adhesive dressing on participants’ forearms.
All participants were vaccinated on the same day, with their clinical response/dermal reaction assessed 3 days later. On day 28, everyone was given albendazole, an anti-parasitic medication, to clear any vaccine-derived larvae, followed by a 2-week washout period, after which the vaccine procedure was repeated. Two weeks later, all participants were challenged with 30 hookworm larvae — 15 in each arm. They were reviewed over the next 10 weeks, provided three fecal samples and received albendazole at the end of the period. All told, the trial took about 6 months, Chapman said.
The average age of participants was about 40-45, the majority were men, nearly all were white and they were slightly overweight, with a mean BMI of 27.
During the trial, there were 228 adverse events (AEs) reported — the most common being vaccine site itch. There were no serious AEs, no change in hemoglobin or hematocrit and no patients required albendazole rescue for gastrointestinal symptoms. There were also no systemic AEs, and no reports of fever, Chapman noted.
“Sensitization to larvae” occurred after repeated vaccination, with a dermal reaction consisting of “blistering and exudate” that became more pronounced, progressing out to the edge of the forearm after the second vaccine and 3 days following the application of larvae.
“Some participants had to wear long sleeves to cover up really florid, angry lesions during the study,” Chapman said.
Indeed, researchers found that 3 days following application of challenge larvae, the area of erythema, or swelling, was significantly larger in the vaccine group versus placebo (594 mm² vs 225 mm², respectively). Induration, or localized hardening of soft tissue, was universal following challenge larvae in the vaccine group (versus only one in the control group). Dermal symptoms also lasted 7 days compared to 2 days, respectively, following challenge larvae, they noted.
Exploratory analyses examined the number of N. americanus larvae in participants’ stool via quantitative polymerase chain reaction, and found the control group recovered a median of 10 larvae/feces cultured compared to 0.8 in the vaccine group. Chapman also noted lower fecal N. americanus DNA intensity in the vaccine versus control group.
“Significantly fewer larvae recovered at coproculture may be a clinically relevant outcome and correlated with a lower fecal DNA intensity,” Chapman said.
However, he noted the trial was underpowered for efficacy, and if the trial was repeated with 30 participants, it could be powered appropriately.
Chapman disclosed no relevant relationships with industry.
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Source: MedicalNewsToday.com
