Phase 1 Study in Malaria Naïve Adults of BSAM2/Alhydrogel®+CPG 7909, a Blood Stage Vaccine against <em>P. falciparum</em> Malaria

<div><p>A Phase 1 dose escalating study was conducted in malaria naïve adults to assess the safety, reactogenicity, and immunogenicity of the blood stage malaria vaccine BSAM2/Alhydrogel®+ CPG 7909. BSAM2 is a combination of the FVO and 3D7 alleles of recombinant AMA1 and MSP1₄₂, with equal amounts by weight of each of the four proteins mixed, bound to Alhydrogel®, and administered with the adjuvant CPG 7909. Thirty (30) volunteers were enrolled in two dose groups, with 15 volunteers receiving up to three doses of 40 µg total protein at Days 0, 56, and 180, and 15 volunteers receiving up to three doses of 160 µg protein on the same schedule. Most related adverse events were mild or moderate, but 4 volunteers experienced severe systemic reactions and two were withdrawn from vaccinations due to adverse events. Geometric mean antibody levels after two vaccinations with the high dose formulation were 136 µg/ml for AMA1 and 78 µg/ml for MSP1₄₂. Antibody responses were not significantly different in the high dose versus low dose groups and did not further increase after third vaccination. <em>In vitro</em> growth inhibition was demonstrated and was closely correlated with anti-AMA1 antibody responses. A Phase 1b trial in malaria-exposed adults is being conducted.</p> <h3>Trial Registration</h3><p>Clinicaltrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT00889616">NCT00889616</a></p> </div

Antibody responses shown are the arithmetic mean of the FVO and 3D7 responses for each antigen for all volunteers who received all 3 vaccines and were not excluded per protocol (n = 23).

<p>Thicker lines show the geometric mean response; arrows indicate vaccinations. Mann-Whitney tests with Hodges-Lehmann confidence intervals were done to compare responses in low versus high dose groups and 2 weeks after 2^nd and 3^rd vaccinations (days 70 and 194); although the 160 µg group had slightly higher geometric means (AMA1 D70: Fold Change = 1.49 [95% CI 0.78, 2.92] p = 0.28; AMA1 D194: FC = 1.30 [0.68, 2.49] p = 0.61;MSP1 D70: FC = 1.18 [0.57,2.49] p = 0.70; MSP1 D 194: FC = 1.30 [0.85, 1.91]) p = 0.21; differences were not significant at the 0.05 level.</p

Correlation between average anti-AMA1 and -MSP1₄₂ antibody responses at Day 70 and Day 194 (two weeks after second and third vaccinations).

<p>Day 70: Spearman correlation, r = 0.60 [95% CI 0.23, 0.82]; Day 194: Spearman's correlation, r = 0.75 [0.50,0.89].</p

Local (injection site pain, tenderness, erythema, swelling, induration) and related systemic adverse events after first, second and third vaccinations in the low dose group.

<p>The x-axis shows the number of participants experiencing adverse events, with the highest severity event for each participant after each vaccination shown.</p

Local (injection site pain, tenderness, erythema, swelling, induration) and related systemic adverse events after first, second and third vaccinations in the high dose group.

<p>The x-axis shows the number of participants experiencing adverse events, with the highest severity event for each participant after each vaccination shown. Other systemic adverse events in both high and low dose groups were: diarrhea (1 severe, 2 mild), abdominal pain, nausea, and cough (all mild or moderate).</p

In vitro growth inhibition of homologous 3D7 parasites as a function of specific antibody concentration is shown.

<p>Purified IgG from Day 70 samples (two weeks after the second vaccination) were used at a concentration of 10 mg/mL.</p

Participants flow sheet.

<p>Thirty (30) participants were enrolled, 24 participants completed vaccinations, and 24 completed follow-up to Day 360.</p