Comparison of prepatent and incubation periods.

<p>Kaplan-Meier survival curve showing the percentage of subjects without patent parasitemia by blood smear (blue line) or without symptoms (dashed red line) following challenge.</p

Time from anti-malarial treatment to clearance of peripheral parasitemia.

<p>*Data not available. Subjects were qRT-PCR positive and peripheral blood smear negative at the time of discharge from the hotel. No further daily sampling was performed after discharge until Day 28, at which point all subjects in the study were blood smear and qRT-PCR negative.</p><p>Time from anti-malarial treatment to clearance of peripheral parasitemia.</p

qRT-PCR-based course of parasitemia.

<p>Parasite density based on qRT-PCR measurements are presented individually for each participant.</p

Subject infectivity summary.

1<p>Number of rounds of mosquito feeding exposures required to achieve a total of 5 infective bites, as demonstrated by evidence of a blood meal in the mosquito abdomen and a post-feed sporozoite salivary gland score of +2 or higher. Subject D received a total of 6 infective bites while all other subjects received 5 bites.</p>2<p>Number of days from CHMI to qRT-PCR-positive.</p>3<p>Number of days from CHMI to peripheral blood smear-positive.</p>4<p>Number of days from CHMI to symptomatic.</p>5<p>BS, blood smear.</p><p>Subject infectivity summary.</p

Study flow diagram.

<p>Eighteen subjects were screened for eligibility to participate in the trial and 7 healthy volunteers were considered eligible and willing to participate. On the day of enrollment, 6 subjects were enrolled and one backup subject was discharged from the study. The six subjects underwent CHMI and completed the 56 day study. Five subjects returned for optional long term safety and immunology follow up assessments at 3 and 6 months post-challenge.</p

Humoral immune responses to <i>P. falciparum</i> antigens.

<p>ELISAs were performed on the indicated days post-CHMI to test for responses against the indicated <i>P. falciparum</i> antigens. The positivity cut-off (dotted line) was calculated per ELISA plate as three standard deviations above the mean of the two negative control wells. All samples with an OD higher than the calculated cut-off were deemed positive. Data are presented for the five subjects completing the follow up at 3 and 6 months. Data to Day 56 for the sixth subject did not differ considerably from the five subjects in the graph.</p

Incidence of adverse events during the 28 days following CHMI.

1<p>A single subject accounted for all severe AEs which appeared on the day of positive blood smear, and all of which decreased in severity within 24 hours of treatment.</p>2<p>Per episode (number of episodes/subjects reporting episodes).</p>3<p>Only symptoms reported from day 0 through day 5 are included.</p>4<p>Only symptoms reported from day 6 through day 28 and determined by the Investigator to be malaria-related are included.</p>5<p>Collected throughout the 56 day study.</p><p>Incidence of adverse events during the 28 days following CHMI.</p

Cellular immune response to CSP and LSA-1.

<p>IFNγ ELISpot assays were performed using the indicated CSP and LSA-1 peptide pools on the indicated days post-CHMI. Spot forming units (SFU) per million PBMC are shown per individual subject for all six subjects.</p

Safety and Immunogenicity of Pfs25-EPA/Alhydrogel^®, a Transmission Blocking Vaccine against <i>Plasmodium falciparum</i>: An Open Label Study in Malaria Naïve Adults

<div><p>Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from <i>Pseudomonas aeruginosa</i>. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel^®. Thirty malaria-naïve healthy adults received up to four doses of the conjugate vaccine, with 8, 16, or 47 μg of conjugated Pfs25 mass, at 0, 2, 4, and 10 months. Vaccinations were generally well tolerated. The majority of solicited adverse events were mild in severity with pain at the injection site the most common complaint. Anemia was the most common laboratory abnormality, but was considered possibly related to the study in only a minority of cases. No vaccine-related serious adverse events occurred. The peak geometric mean anti-Pfs25 antibody level in the highest dose group was 88 (95% CI 53, 147) μg/mL two weeks after the 4^th vaccination, and declined to near baseline one year later. Antibody avidity increased over successive vaccinations. Transmission blocking activity demonstrated in a standard membrane feeding assay (SMFA) also increased from the second to the third dose, and correlated with antibody titer and, after the final dose, with antibody avidity. These results support the further evaluation of Pfs25-EPA/Alhydrogel^® in a malaria-endemic population.</p></div

Immunofluorescence assays with immune sera.

<p>A. Surface labeling of zygotes with sera from one volunteer (#20) collected on days 0, 314 and 356, with Pfs25 specific mouse mAbs 1G2 and 4B7. B. Recognition of parasite protein in fixed ookinetes with sera from one volunteer (#20) collected on days 0, 314 and 356, with Pfs25 specific mouse mAb 4B7. Magnification 1000X.</p