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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

Breadth and magnitude of IgG responses to GS and NGS peptides before and after the malaria season. (A) Each symbol represents the percentage of peptides with IgG reactivity (breadth) in an individual plasma sample (n = 223 subjects before season; n = 195 subjects after season). (B) Each symbol represents the average IgG reactivity (magnitude) against 194 GS peptides or 126 NGS peptides in individual plasma samples. Symbol color indicates the subject's age group. Lines and whiskers represent means and standard deviations, respectively. P values determined by a linear mixed model with Bonferroni-adjusted contrasts. ***, P < 0.001.
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Figure 1: Breadth and magnitude of IgG responses to GS and NGS peptides before and after the malaria season. (A) Each symbol represents the percentage of peptides with IgG reactivity (breadth) in an individual plasma sample (n = 223 subjects before season; n = 195 subjects after season). (B) Each symbol represents the average IgG reactivity (magnitude) against 194 GS peptides or 126 NGS peptides in individual plasma samples. Symbol color indicates the subject's age group. Lines and whiskers represent means and standard deviations, respectively. P values determined by a linear mixed model with Bonferroni-adjusted contrasts. ***, P < 0.001.

Mentions: We first sought to understand the relative immunogenicity of GS and NGS proteins by examining both the breadth and magnitude of GS and NGS IgG responses at two time points: after the 6-month dry season (a period of negligible P. falciparum transmission) and after the 6-month malaria season (a period during which nearly all study subjects are infected with P. falciparum in this area of Mali) (40). We defined the “breadth” for each plasma sample as the number of proteins to which the level of IgG reactivity exceeded 2 SD above the negative (no DNA) control. Because the numbers of GS and NGS proteins differed, we present the data as the percentages of GS and NGS proteins that were reactive in each plasma sample. We found that the average percentage of reactive GS proteins increased from before to after the malaria season (Fig. 1A; GS mean before: 21.7% [SD 15.6%]; GS mean after: 30.0% [SD 16.7%]; P < 0.001), and likewise, the average percentage of reactive NGS proteins increased from before to after the malaria season (Fig. 1A; NGS mean before: 30.2% [SD = 17.8%]; NGS mean after: 41.2% [SD 18.2%]; P < 0.001). On average, the percentage of GS proteins that were reactive before the malaria season was significantly lower than the percentage of NGS proteins that were reactive at the same time point (P < 0.001) (Fig. 1A). Similarly, the average percentage of GS proteins that were reactive after the malaria season was significantly lower than the percentage of NGS proteins that were reactive at the same time point (P < 0.001) (Fig. 1A).


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)

Breadth and magnitude of IgG responses to GS and NGS peptides before and after the malaria season. (A) Each symbol represents the percentage of peptides with IgG reactivity (breadth) in an individual plasma sample (n = 223 subjects before season; n = 195 subjects after season). (B) Each symbol represents the average IgG reactivity (magnitude) against 194 GS peptides or 126 NGS peptides in individual plasma samples. Symbol color indicates the subject's age group. Lines and whiskers represent means and standard deviations, respectively. P values determined by a linear mixed model with Bonferroni-adjusted contrasts. ***, P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Breadth and magnitude of IgG responses to GS and NGS peptides before and after the malaria season. (A) Each symbol represents the percentage of peptides with IgG reactivity (breadth) in an individual plasma sample (n = 223 subjects before season; n = 195 subjects after season). (B) Each symbol represents the average IgG reactivity (magnitude) against 194 GS peptides or 126 NGS peptides in individual plasma samples. Symbol color indicates the subject's age group. Lines and whiskers represent means and standard deviations, respectively. P values determined by a linear mixed model with Bonferroni-adjusted contrasts. ***, P < 0.001.
Mentions: We first sought to understand the relative immunogenicity of GS and NGS proteins by examining both the breadth and magnitude of GS and NGS IgG responses at two time points: after the 6-month dry season (a period of negligible P. falciparum transmission) and after the 6-month malaria season (a period during which nearly all study subjects are infected with P. falciparum in this area of Mali) (40). We defined the “breadth” for each plasma sample as the number of proteins to which the level of IgG reactivity exceeded 2 SD above the negative (no DNA) control. Because the numbers of GS and NGS proteins differed, we present the data as the percentages of GS and NGS proteins that were reactive in each plasma sample. We found that the average percentage of reactive GS proteins increased from before to after the malaria season (Fig. 1A; GS mean before: 21.7% [SD 15.6%]; GS mean after: 30.0% [SD 16.7%]; P < 0.001), and likewise, the average percentage of reactive NGS proteins increased from before to after the malaria season (Fig. 1A; NGS mean before: 30.2% [SD = 17.8%]; NGS mean after: 41.2% [SD 18.2%]; P < 0.001). On average, the percentage of GS proteins that were reactive before the malaria season was significantly lower than the percentage of NGS proteins that were reactive at the same time point (P < 0.001) (Fig. 1A). Similarly, the average percentage of GS proteins that were reactive after the malaria season was significantly lower than the percentage of NGS proteins that were reactive at the same time point (P < 0.001) (Fig. 1A).

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