Novel Malaria Vaccine Shows Activity Only at Peak Titers
Pfs25H-EPA vaccine was well tolerated and induced significant serum activity by standard assays but transmission-blocking activity was not confirmed by weekly direct skin feed.
A malaria transmission-blocking vaccine, Pfs25H-EPA in Alhydrogel®, was well tolerated and safe and induced significant blockage of parasite transmission, but this activity was only seen at peak titers after 4 vaccine doses, according to a report published in The Lancet Infectious Diseases.
Pfs25H-EPA is a protein-protein conjugate transmission-blocking vaccine against Plasmodium falciparum and has demonstrated safety and the ability to induce antibodies in malaria-naïve individuals. This study assessed the vaccine for safety and functional immunogenicity in malaria-exposed adults residing in Mali. An initial pilot safety assessment was conducted, followed by a main phase. Participants (10 in each arm) in the pilot cohort received 2 doses of Pfs25H-EPA/Alhydrogel 16 µg or Euvax B as a comparator, while participants in the main phase (50 in each arm) received Pfs25H-EPA/Alhydrogel 47 µg or comparator vaccine (Euvax B for vaccines 1-3 and Menactra® for vaccine 4).
Pfs25H antibody titers increased with each vaccine dose and reached a peak geometric mean of 422.3 enzyme-linked immunosorbent assay (ELISA) units (95% CI, 290-615) after the fourth dose. However, the mean declined relatively rapidly; investigators report a half-life of 42 days for anti-Pfs25H and 59 days for anti-EPA (median ratio of titers at day 600 to peak, 0.19 for anti-Pfs25H vs 0.29 for anti-EPA; P =.009). Following the fourth dose, serum transmission-reducing activity was greater for Pfs25H vs the comparator (P <.001) but not after the third dose (P =.09).
“The findings from our study in Mali are the first to show that functional transmission-blocking antibodies can be induced in the target population, and they lay the foundation for further development of this class of vaccine that can contribute to malaria elimination and eradication,” concluded the investigators.
Sagara I, Healy SA, Assadou MH, et al. Safety and immunogenicity of Pfs25H-EPA/Alhydrogel, a transmission-blocking vaccine against Plasmodium falciparum: a randomised, double-blind, comparator-controlled, dose-escalation study in healthy Malian adults. [published online Jul 27, 2018] Lancet Infect Dis. doi:10.1016/S1473-3099(18)30344-X