Virosome-Formulated Plasmodium falciparum AMA-1 & CSP Derived Peptides as Malaria Vaccine: Randomized Phase 1b Trial in Semi-Immune Adults & Children

Abstract

BackgroundThis trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children.MethodsThe design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations. 10 adults and 40 children (aged 5–9 years) living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal®V on day 0 and 90.ResultsNo serious or severe adverse events (AEs) related to the vaccines were observed. The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal®V group compared to the PEV3B group (p = 0.014). In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal®V control group. Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children. As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (0.0035 episodes per day at risk for PEV3B vs. 0.0069 for Inflexal®V; RR = 0.50 [95%-CI: 0.29–0.88], p = 0.02).ConclusionThese findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines.Trial RegistrationClinicalTrials.gov NCT00513669

Antibody and T‐cell responses associated with experimental human malaria infection or vaccination show limited relationships

“…PEV3 malaria vaccine 9 ) to generate high-titre antibodies, the magnitude of which is associated with protection both in malaria-naive vaccinees 9 and in the field. 10 Furthermore, these vaccine-generated antibodies inhibit invasion of hepatocytes by sporozoites in vitro. The role of anti-influenza T cells as cognate help for antibody production in the latter has been suggested, 11 but not thoroughly explored.…”

“…Previous power calculations using Fisher's 'arctanh' transformation, and based on numerous previous studies, [6][7][8][9][10][11]28,29 suggested that data from 12 individuals would sufficiently power statistical analysis when moderate to large effect sizes (r of at least 0Á50) were observed. Spearman's test was used for correlation analysis while the Student's t-test or Mann-Whitney U-test was used to compare means of log-transformed data.…”

Passive Immunoprotection of Plasmodium falciparum-Infected Mice Designates the CyRPA as Candidate Malaria Vaccine Antigen

“…Unfortunately, the most advanced blood-stage vaccine Ags, AMA-1 and MSP-1, have not demonstrated efficacy in African children to date (14,34,35). However, a multistage vaccine comprising an AMA-1 component showed a 50% reduced incidence rate of clinical malaria episodes in child vaccinees compared with that of control children (36). But whether protection is associated with AMA-1-specific responses remains to be shown.…”

Virosome, a hybrid vehicle for efficient and safe drug delivery and its emerging application in cancer treatment

“…So far, virosomes have successfully delivered anti-cancer, anti-malarial, anti-bacterial, and anti-fungal agents in vitro and in vivo (60)(61)(62)(63)(64). However, because of our research interests, in the current review, we will mostly focus on the application of virosomes in cancer treatment.…”