Anti-Pfs25 antibody titer of EPA, TT or CRM conjugates of Pfs25 synthesized by thioether (TE) chemistry formulated in either Alhydrogel (AH) or AdjuPhos (AP).

<p>Immune sera were collected from Day 42 after two vaccinations were analyzed. Dose: 0.5 μg/mouse.</p

Anti-Pfs25 or Pfs230D1 antibody titer of EPA conjugates of Pfs25 and Pfs230D1 synthesized by thioether (TE) and Amide (Am) conjugation chemistry.

<p>Mice were immunized with conjugates formulated in saline or Alhydrogel. Sera were analyzed on Day 42 after vaccination on Day 0 and 28. Dose: 0.5 μg/mouse.</p

Physico-chemical parameters of Pfs25 -EPA conjugates with different molecular weight and particle size used in the mice study evaluating the effect of size on the immunogenicity (Fig 5).

<p>Physico-chemical parameters of Pfs25 -EPA conjugates with different molecular weight and particle size used in the mice study evaluating the effect of size on the immunogenicity (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0190312#pone.0190312.g005" target="_blank">Fig 5</a>).</p

Le Courrier

31 mars 18261826/03/31 (A0,N90)

Physico-chemical parameters of various conjugates of PfCSP, Pfs25 and Pfs230D1 with EPA, TT or CRM197.

<p>Physico-chemical parameters of various conjugates of PfCSP, Pfs25 and Pfs230D1 with EPA, TT or CRM197.</p

Anti-Pfs25 antibody titer of EPA conjugates of Pfs25 with varying average molecular weight and particle size, synthesized by thioether (TE) chemistry, formulated in either saline or Alhydrogel (AH).

<p>Immune sera collected on Day 42 (left panel) or 70 (right panel) were analyzed by ELISA. Vaccinations on Days 0 and 28. Doses: 0.5 μg or 0.1 μg/mouse/injection as indicated.</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

Summary of adverse events after each vaccination.

<p>Clinical solicited (A-C) and Laboratory (D-F) adverse events after each vaccination with each dose group are reported in individual graphs: Group 1a (A and D), 1b (B and E) and Group 2 (C and F). All adverse events were mild except when indicated as moderate.</p

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

Study flow chart.

<p>Thirty (30) participants were enrolled, 23 completed the study per protocol.</p