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Controlled Clinical Trial
. 2008 Jul 1;198(1):134-42.
doi: 10.1086/588711.

Antibodies to Plasmodium falciparum and Plasmodium vivax merozoite surface protein 5 in Indonesia: species-specific and cross-reactive responses

Tonia Woodberry  1 , Gabriela Minigo, Kim A Piera, Jennifer C Hanley, Harini D de Silva, Ervi Salwati, Enny Kenangalem, Emiliana Tjitra, Ross L Coppel, Ric N Price, Nicholas M Anstey, Magdalena Plebanski
Affiliations
Controlled Clinical Trial

Antibodies to Plasmodium falciparum and Plasmodium vivax merozoite surface protein 5 in Indonesia: species-specific and cross-reactive responses

Tonia Woodberry et al. J Infect Dis. .

Abstract

Background: Merozoite surface protein (MSP) 5 is a candidate antigen for a malaria vaccine. In cross-sectional and longitudinal studies, we measured MSP5 antibody responses in Papuans with acute Plasmodium falciparum malaria, Plasmodium vivax malaria, and mixed P. falciparum and P. vivax malaria and in those with past exposure.

Methods: Enzyme-linked immunosorbant assay (ELISA) was used to quantitate antibody responses to P. falciparum MSP5 (PfMSP5) and P. vivax MSP5 (PvMSP5) in 82 subjects with P. falciparum infection, 86 subjects with P. vivax infection, 85 subjects with mixed infection, and 87 asymptomatic individuals. Longitudinal responses through day 28 were tested in 20 persons. Cross-reactivity was tested by competition ELISA.

Results: PfMSP5 or PvMSP5 immunoglobulin (Ig)Gwas detected in 39%-52% of subjects, and IgM was detected in 44%-72%. IgG responses were distributed equally between IgG3 and IgG1 for PfMSP5 but were predominantly IgG3 for PvMSP5. Although IgG responses were generally specific for PfMSP5 or PvMSP5, cross-species reactivity was found in 7 of 107 dual-positive responders. No significant difference was seen in the magnitude, frequency, or subclass of PfMSP5 or PvMSP5 IgG antibodies between groups. There was no significant association between antibody responses and therapeutic response.

Conclusion: PfMSP5 and PvMSP5 were frequently recognized by short-lived, species-specific antibodies. Although infrequent, the cross-reactive MSP5 antibodies indicate that an appropriately formulated vaccine may elicit and/or enhance cross-species recognition, which may be very useful in areas where both parasites are endemic.

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Figures

Figure 1
Figure 1
Total plasma IgG specific for merozoite surface protein (MSP) 5 of Plasmodium falciparum (PfMSP5) (A) or MSP5 of Plasmodium vivax (PvMSP5) (B) and IgM specific for PfMSP5 (C) and PvMSP5 (D) in asymptomatic subjects exposed to Plasmodium species (n = 87) and in subjects with acute P. falciparum (Pf; n = 82), acute P. vivax (Pv; n = 86), or acute mixed (Pf & Pv; n = 85) infection. Solid horizontal lines indicate geometric means, and dotted lines indicate cutoffs for positive responses (mean optical density plus 3 SDs for 36 unexposed blood donors).
Figure 2
Figure 2
IgG cross-reactivity between merozoite surface protein (MSP) 5 of Plasmodium falciparum (PfMSP5) and MSP5 of Plasmodium vivax (PvMSP5). Plasma samples were preincubated with titrating concentrations of PfMSP5 or PvMSP5 before being tested for remaining IgG specific for PfMSP5 (triangles) or PvMSP5 (squares) by ELISA. Black symbols represent preincubation with the same protein as tested in the ELISA, and white symbols represent preincubation with MSP5 from the other species. Results for 4 representative donors are shown: PvMSP5 IgG only (A), PfMSP5 IgG only (B), IgG to both PfMSP5 and PvMSP5 with no cross-reactivity (C), and IgG to both PfMSP5 and PvMSP5 with some cross-reactivity (D).
Figure 3
Figure 3
Longitudinal merozoite surface protein 5 (MSP) 5 responses. Shown are IgM and IgG antibody responses to Plasmodium falciparum (Pf) MSP5 (PfMSP5) (left panels) and Plasmodium vivax (Pv) MSP5 (PvMSP5) (right panels) in plasma collected on the day of treatment (day 0) and 7 and 28 days later. Subjects had MSP5-specific IgM but no IgG responses (A) or both IgM and IgG responses (B) (4 representative donors are shown). Horizontal dotted lines indicate the thresholds for positive IgM (lower line) and IgG (upper line) responses.
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