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Plasmodium falciparum Gametocyte-Specific Antibody Profiling Reveals Boosting through Natural Infection and Identifies Potential Markers of Gametocyte Exposure.

Skinner J, Huang CY, Waisberg M, Felgner PL, Doumbo OK, Ongoiba A, Kayentao K, Traore B, Crompton PD, Williamson KC - Infect. Immun. (2015)

Bottom Line: Malaria elimination efforts would benefit from vaccines that block transmission of Plasmodium falciparum gametocytes from humans to mosquitoes.Using publicly available proteomic data, we classified 91 proteins as gametocyte specific and 69 as proteins not expressed by gametocytes.In addition, IgGs specific for the gametocyte proteins Pfmdv1, Pfs16, PF3D7_1346400, and PF3D7_1024800 were detected in nearly all subjects, suggesting that seroconversion to these proteins may be a sensitive indicator of gametocyte exposure, although further studies are needed to determine the specificity and kinetics of these potential serologic markers.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.

No MeSH data available.


Related in: MedlinePlus

IgG reactivity to TBV candidates Pfs25, Pfs48/45 and Pfs230 before the malaria season. (A) Schematic of Pfs230 indicating the location of the peptides (s1 to s4) used on the microarray in relation to the secretory signal sequence (S), the glutamate repeat regions (E), the proteolytic processing site (arrow), and the seven 6-cysteine domains (CM1 to CM7). The amino acids (aa) and base pairs (bp) corresponding to the start and end of peptides s1 to s4 are indicated. (B to F) Symbols represent the level of IgG reactivity against Pfs25 (B), Pfs48/45 (C), Pfs16 (D), Pfmdv1 (E), and Pfs230 (F) s1 to s4 in individual plasma samples (n = 223 subjects before season; n = 195 subjects after season). Lines and whiskers represent means and standard deviations, respectively. FDR-adjusted P values determined by eBayes moderated t tests of 2,221 antigen fragments recognized in at least 20% of all samples.
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Figure 2: IgG reactivity to TBV candidates Pfs25, Pfs48/45 and Pfs230 before the malaria season. (A) Schematic of Pfs230 indicating the location of the peptides (s1 to s4) used on the microarray in relation to the secretory signal sequence (S), the glutamate repeat regions (E), the proteolytic processing site (arrow), and the seven 6-cysteine domains (CM1 to CM7). The amino acids (aa) and base pairs (bp) corresponding to the start and end of peptides s1 to s4 are indicated. (B to F) Symbols represent the level of IgG reactivity against Pfs25 (B), Pfs48/45 (C), Pfs16 (D), Pfmdv1 (E), and Pfs230 (F) s1 to s4 in individual plasma samples (n = 223 subjects before season; n = 195 subjects after season). Lines and whiskers represent means and standard deviations, respectively. FDR-adjusted P values determined by eBayes moderated t tests of 2,221 antigen fragments recognized in at least 20% of all samples.

Mentions: Although the overall GS IgG response clearly increased with malaria transmission, it remained possible that antigens constituting current TBV candidates do not elicit IgG responses in the context of natural P. falciparum infection. The protein microarray included peptides corresponding to the TBV candidates Pfs25, Pfs48/45, and Pfs230. Due to its large size, Pfs230 was represented on the microarray as four peptides (s1 to s4), the amino-terminal peptide of which (s1) contains the site reported to be a target for transmission-blocking antibodies (Fig. 2A) (41, 42). For each of these proteins/peptides, we determined the seroprevalence as well as average IgG reactivity before and after the 6-month malaria season.


Plasmodium falciparum Gametocyte-Specific Antibody Profiling Reveals Boosting through Natural Infection and Identifies Potential Markers of Gametocyte Exposure.

Skinner J, Huang CY, Waisberg M, Felgner PL, Doumbo OK, Ongoiba A, Kayentao K, Traore B, Crompton PD, Williamson KC - Infect. Immun. (2015)

IgG reactivity to TBV candidates Pfs25, Pfs48/45 and Pfs230 before the malaria season. (A) Schematic of Pfs230 indicating the location of the peptides (s1 to s4) used on the microarray in relation to the secretory signal sequence (S), the glutamate repeat regions (E), the proteolytic processing site (arrow), and the seven 6-cysteine domains (CM1 to CM7). The amino acids (aa) and base pairs (bp) corresponding to the start and end of peptides s1 to s4 are indicated. (B to F) Symbols represent the level of IgG reactivity against Pfs25 (B), Pfs48/45 (C), Pfs16 (D), Pfmdv1 (E), and Pfs230 (F) s1 to s4 in individual plasma samples (n = 223 subjects before season; n = 195 subjects after season). Lines and whiskers represent means and standard deviations, respectively. FDR-adjusted P values determined by eBayes moderated t tests of 2,221 antigen fragments recognized in at least 20% of all samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4598406&req=5

Figure 2: IgG reactivity to TBV candidates Pfs25, Pfs48/45 and Pfs230 before the malaria season. (A) Schematic of Pfs230 indicating the location of the peptides (s1 to s4) used on the microarray in relation to the secretory signal sequence (S), the glutamate repeat regions (E), the proteolytic processing site (arrow), and the seven 6-cysteine domains (CM1 to CM7). The amino acids (aa) and base pairs (bp) corresponding to the start and end of peptides s1 to s4 are indicated. (B to F) Symbols represent the level of IgG reactivity against Pfs25 (B), Pfs48/45 (C), Pfs16 (D), Pfmdv1 (E), and Pfs230 (F) s1 to s4 in individual plasma samples (n = 223 subjects before season; n = 195 subjects after season). Lines and whiskers represent means and standard deviations, respectively. FDR-adjusted P values determined by eBayes moderated t tests of 2,221 antigen fragments recognized in at least 20% of all samples.
Mentions: Although the overall GS IgG response clearly increased with malaria transmission, it remained possible that antigens constituting current TBV candidates do not elicit IgG responses in the context of natural P. falciparum infection. The protein microarray included peptides corresponding to the TBV candidates Pfs25, Pfs48/45, and Pfs230. Due to its large size, Pfs230 was represented on the microarray as four peptides (s1 to s4), the amino-terminal peptide of which (s1) contains the site reported to be a target for transmission-blocking antibodies (Fig. 2A) (41, 42). For each of these proteins/peptides, we determined the seroprevalence as well as average IgG reactivity before and after the 6-month malaria season.

Bottom Line: Malaria elimination efforts would benefit from vaccines that block transmission of Plasmodium falciparum gametocytes from humans to mosquitoes.Using publicly available proteomic data, we classified 91 proteins as gametocyte specific and 69 as proteins not expressed by gametocytes.In addition, IgGs specific for the gametocyte proteins Pfmdv1, Pfs16, PF3D7_1346400, and PF3D7_1024800 were detected in nearly all subjects, suggesting that seroconversion to these proteins may be a sensitive indicator of gametocyte exposure, although further studies are needed to determine the specificity and kinetics of these potential serologic markers.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.

No MeSH data available.


Related in: MedlinePlus