Invited Speaker Australian Society for Microbiology Annual Scientific Meeting 2021

A phase 1b clinical trial to assess safety and efficacy of an attenuated hookworm larvae vaccine (#108)

Alex Loukas 1 , Paul Chapman 2 , Paul Giacomin 1 , Peter O'Rourke 2 , Stacey Llewellyn 2 , Christian Engwerda 2 , Luke Becker 1 , James S McCarthy 2
  1. Australian Institute of Tropical Health and Medicine, James Cook University , Queensland, Australia
  2. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

Control of human hookworm infection through mass drug administration is impeded by high rates of reinfection, leading to the proposal for a human hookworm vaccine. We hypothesised that percutaneous exposure to Necator americanus larvae (L3) attenuated with ultraviolet C (UVC) light would result in protective immunity. We conducted a phase 1b clinical trial using an attenuated L3 vaccine delivered via dermal application to healthy human volunteers. Immune response and protective efficacy were secondary endpoints. Fifteen healthy, hookworm-naive volunteers were randomised (1:2) to receive placebo (tabasco sauce) or vaccine (50 attenuated L3) via dermal application. L3 were attenuated by exposure to 700mJ of UVC. Two cycles of placebo or vaccine were administered 6 weeks apart, followed 6 weeks later by challenge with 30 unattenuated L3. Significantly more adverse events (AEs) were observed following vaccination with attenuated larvae compared with placebo (p=0∙003), but there was no difference between groups in the frequency of AEs following challenge. The majority of AEs were mild in severity, with only one severe AE (erythematous and indurated pruritic rash greater than 100 mm in a vaccinated participant post-challenge). The eosinophil count increased in all participants after challenge, with a significantly greater increase among vaccinated participants compared to placebo participants (p=0·014). Vaccinated participants mounted a robust humoral and cellular response to the vaccine. Significantly fewer larvae per gram of faeces were recovered in the vaccinated group than in the placebo group after challenge (p=0∙014). Vaccination with UVC-attenuated Necator americanus larvae is well tolerated, induces humoral and cellular responses to hookworm antigens, and reduces larval output after challenge with unattenuated larvae. Larger studies are required to confirm protective efficacy. Immunomics-based studies are underway to identify the specific antigen targets of protective immunity with a view to ultimate development of a multivalent subunit vaccine that targets different developmental stages of the parasite.