A malaria transmission-blocking vaccine was well tolerated and safe in in Malian adults, according to study results recently published in The Lancet Infectious Diseases.
“We tested the safety of Pfs25H-EPA/Alhydrogel and whether functional antibody induced in Malian adults who receive Pfs25H-EPA/Alhydrogel reduced parasite transmission to Anopheles stephensi mosquitoes in laboratory assays and to Angopheles coluzzii in direct skin feed assays,” the researchers wrote.
Pfs25H-EPA is a protein-protein conjugate transmission blocking vaccine against Plasmodium falciparum, the deadliest of human malaria parasite species, the researchers noted.
They conducted a double-blind, comparator-controlled, dose-escalation study in Bancoumana, Mali, in two phases, including an initiation pilot safety assessment and main phase. Study eligibility included being a healthy village resident aged 18 to 45 years willing to participate in mosquito direct skin feeding (DSF) assays. Exclusion criteria included abnormal laboratory test results for HIV, hepatitis B and hepatitis C or having received a previous malaria vaccine or recent immunosuppressive drugs, vaccines or blood products.
Patients were randomly assigned in both the pilot safety study and main cohort. Researchers administered two doses of Pfs25H-EPA/Alhydrogel 16 g or the comparator vaccine, Euvax B (LG Chem Life Sciences Company), a recombinant hepatitis B vaccine, in the pilot study, and Pfs25H-EPA/Alhydrogel 47 g or the compactor vaccine of Euvax B for the first, second and third vaccinations and Menactra (Sanofi Pasteur) for the fourth vaccination.
Participants and investigators were masked to group assignments until the final study visit. The study drugs also were masked.
Safety and tolerability for all vaccines were the primary outcomes, whereas immunogenicity 14 days after vaccination was the secondary outcome.
The researchers screened 230 individuals from May 15 to June 16, 2013. Twenty were enrolled in the pilot study, with 10 participants assigned Pfs25H-EPA/Alhydrogel 16 g and 10 assigned the comparator vaccine. One hundred participants were enrolled in the main cohort study, with 50 assigned Pfs25H-EPA/Alhydrogel 47 g and 50 assigned the comparator vaccine.
The Pfs25H-EPA vaccines had 137 solicited adverse events compared with 86 solicited adverse events for the comparator vaccines (P = .022) and 191 treatment-related adverse events compared with 126 for the comparator vaccines (P = .034). There was not a significant difference in other adverse events between the two cohorts.
There was an increase in Pfs25H antibody titers with each dose, and a peak geometric mean of 422.3 ELISA units after the fourth dose, followed by a rapid decrease. PfS25H-EPA had greater serum transmission-reducing activity than the comparator vaccine after the fourth vaccine dose (P < .001) but not after the third dose (P = .09).
The researchers reported that DSFs were well tolerated. The two cohorts did not differ in the number of patients who infected at least one mosquito after the fourth dose.
“The Pfs25H-EPA/Alhydrogel vaccine candidate was safe and immunogenic in Malian adults and induced significant serum activity after four doses that reduced parasite transmission to mosquitoes in a laboratory assay,” the researchers concluded. “In this first field trial of a transmission-blocking vaccine against malaria, functional immunogenicity in the target population was achieved despite lifetime exposure to P. falciparium; however, transmission-blocking activity was incomplete, and Pfs25H antibody titers decreased rapidly. Future studies should seek to increase and prolong functional antibody activity, possibly by combining Pfs25 with another antigen such as Pfs230, and to measure vaccine activity against naturally circulating infections.”
In a related editorial, Tomoko Ishino and Takafumi Tsuboi of the Proteo-Science Center, Ehime University, Japan, noted that Pfs25 has been extensively studied for nearly 30 years in the development of a transmission-blocking vaccine.
“The data will strengthen the momentum toward developing a robust transmission-blocking vaccine that is essential for malaria elimination,” they wrote.
“Although the results of the DSF assays showed no significant differences in the proportions of infective participants in the Pfs25 and comparator vaccine groups, the successful application of the approach marks an important milestone in determination of actual transmission-blocking activity in humans.” – by Bruce Thiel
The researchers report no relevant financial disclosures.