Sagara I, et al. - Researchers performed a field trial to assess the safety and functional immunogenicity of Pfs25H-EPA/Alhydrogel, a transmission-blocking vaccine against Plasmodium falciparum, in Malian adults. Patients well tolerated Pfs25H-EPA/Alhydrogel. It induced significant serum activity by standard membrane feeding assays but its transmission blocking activity was not established by weekly direct skin feed. Four doses were required for this activity, and rapid decrease in titres was observed after the fourth dose.

Methods

• In Bancoumana, Mali, researchers performed this double-blind, randomised, comparator-controlled, dose-escalation trial; this trial was performed in two staggered phases, an initial pilot safety assessment and a subsequent main phase.
• Eligibility criteria for inclusion was healthy village residents (aged 18–45 years) with normal laboratory results (including HIV, hepatitis B, hepatitis C tests), and no previously received malaria vaccine or recent immunosuppressive drugs, vaccines, or blood products.
• They assigned participants in the pilot safety cohort and the main cohort (1:1) by block randomisation to a study vaccine group.
• Two doses of Pfs25H-EPA/Alhydrogel 16 μg or Euvax B (comparator vaccine) were given to participants in the pilot safety cohort, and Pfs25H-EPA/Alhydrogel 47 μg or comparator vaccine (Euvax B for the first, second, and third vaccinations and Menactra for the fourth vaccination) was given to participants in the main cohort.
• Group assignment, and randomisation codes were masked to participants and investigators in sealed envelopes held by a site pharmacist.
• They covered the vials with study drug for injection with opaque tape and labelled them with a study identification number.
• At final study visit, group assignments were unmasked.
• Safety and tolerability for all vaccinees were included as the primary outcomes.
• Immunogenicity 14 days after vaccination in the per-protocol population, as confirmed by the presence of antibodies against Pfs25H measured by ELISA IgG and antibody functionality assessed by standard membrane feeding assays and by direct skin feeding assays was included as the secondary outcome measure. 

Results

• Researchers screened 230 individuals for eligibility between May 15, and Jun 16, 2013.
• The pilot safety cohort included 20 individuals; they assigned ten participants to receive Pfs25H-EPA/Alhydrogel 16 μg, and rest of the ten participants to receive comparator vaccine.
• The main cohort included 100 individuals; they assigned 50 participants to receive Pfs25H-EPA/Alhydrogel 47 μg, and rest of the 50 participants to receive comparator vaccine.
• Compared with comparator vaccinees, Pfs25H vaccinees experienced more solicited adverse events (137 events vs 86 events; p=0·022) and treatment-related adverse events (191 events vs 126 events, p=0·034), but the groups did not differ regarding the number of other adverse events (792 vs 683).
• With each dose, they observed increase in Pfs25H antibody titres with a peak geometric mean of 422·3 ELISA units (95% CI 290–615) after the fourth dose, but thereafter the antibody titres decreased relatively rapidly, with a half-life of 42 days for anti-Pfs25H and 59 days for anti-EPA (median ratio of titres at day 600 to peak, 0·19 for anti-Pfs25H vs 0·29 for anti-EPA; p=0·009).
• After the fourth vaccine dose, Pfs25H vs comparator vaccine showed greater serum transmission-reducing activity (p<0·001) but this was not noted after the third dose (p=0·09).
• Participants well tolerated repeated direct skin feeds, but after the fourth dose, the number of participants who infected at least one mosquito did not differ between Pfs25H and comparator vaccinees (p=1, conditional exact).