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Exclusion criteria: Studies showing incomplete protection in immunized subjects, or incomplete control infectivity, were excluded.
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Similar to HIV women, CVL from HIV women showed limited enhancement of HIV infectivity beyond control infections (3 of 75 assays).
Immunization studies showing complete protection of all immunized subjects and infectivity in all control infections (in any part of the study), were included in a final dataset for analysis (Defined in Figure 1; listed in Table S1).
Many glycoconjugate compounds are present on the entire cell surface of Trypanosoma brucei to control the infectivity and survival of this pathogen.
Western Blotting against the viral protein IE63 was also performed to control cell infectivity.
Ad.CMV.GFP served as a control for infectivity.
In the genome of the produced HIV viral particles, a firefly luciferase gene (fLuc) is also encoded as an internal control for infectivity of the viruses.
One of the 15 non-vaccinated controls was enrolled as an extra volunteer to replace any infectivity control drop-outs, one was enrolled as a source of malaria-naïve peripheral blood mononuclear cells (PBMC) for cohort 4 (immunological control) and 13 were enrolled as infectivity controls or as both infectivity controls and immunological controls.
The challenge model traditionally used to assess efficacy of pre-erythrocytic vaccine candidates is robust: at WRAIR, a 100% infection rate has been obtained in the last 100 infectivity control volunteers fed upon by 5 Anopheline mosquitoes which were each highly infected with P. falciparum sporozoites.
To assess the efficacy of the vaccines the 24 vaccinated subjects and 6 unvaccinated infectivity control subjects underwent experimental challenge with Plasmodium falciparum, fourteen days after the final vaccination.
Among the three groups (two full dose vaccine groups and infectivity control group), there was a strong, statistically significant difference in longitudinal measurement of peripheral parasitemia on Days 7 9, the days in which peripheral parasitemia was detected and measured by qPCR and no treatment with chloroquine had yet been initiated (p = 0.0002, repeated measures ANOVA, data not shown).
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