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. 2017 Sep 25;12(9):e0185303.
doi: 10.1371/journal.pone.0185303. eCollection 2017.

Variations in the quality of malaria-specific antibodies with transmission intensity in a seasonal malaria transmission area of Northern Ghana

Kwadwo A Kusi  1   2   3 , Emmanuel A Manu  2   3 , Theresa Manful Gwira  2   3 , Eric Kyei-Baafour  1 , Emmanuel K Dickson  1 , Jones A Amponsah  1 , Edmond J Remarque  4 , Bart W Faber  4 , Clemens H M Kocken  4 , Daniel Dodoo  1 , Ben A Gyan  1 , Gordon A Awandare  2   3 , Frank Atuguba  5 , Abraham R Oduro  5 , Kwadwo A Koram  3   6
Affiliations

Variations in the quality of malaria-specific antibodies with transmission intensity in a seasonal malaria transmission area of Northern Ghana

Kwadwo A Kusi et al. PLoS One. .

Abstract

Introduction: Plasmodium falciparum induced antibodies are key components of anti-malarial immunity in malaria endemic areas, but their antigen targets can be polymorphic. Induction of a high proportion of strain-specific antibodies will limit the recognition of a broad diversity of parasite strains by these responses. There are indications that circulating parasite diversity varies with malaria transmission intensity, and this may affect the specificity of elicited anti-malarial antibodies. This study therefore assessed the effect of varying malaria transmission patterns on the specificity of elicited antibody responses and to identify possible antibody correlates of naturally acquired immunity to malaria in children in an area of Ghana with seasonal malaria transmission.

Methods: This retrospective study utilized plasma samples collected longitudinally at six time points from children aged one to five years. Multiplex assays were used to measure antibody levels against four P. falciparum AMA 1 variants (from the 3D7, FVO, HB3 and CAMP parasite strains) and the 3D7 variant of the EBA 175 region II antigen and the levels compared between symptomatic and asymptomatic children. The relative proportions of cross-reactive and strain-specific antibodies against the four AMA 1 variants per sampling time point were assessed by Bland-Altman plots. The levels of antibodies against allelic AMA1 variants, measured by singleplex and multiplex luminex assays, were also compared.

Results: The data show that increased transmission intensity is associated with higher levels of cross-reactive antibody responses, most likely a result of a greater proportion of multiple parasite clone infections during the high transmission period. Anti-AMA1 antibodies were however associated with a history of infection rather than protection in this age group.

Conclusion: The data contribute to understanding the underlying mechanism of the acquisition of strain-transcending antibody immunity following repeated exposure to diverse parasite strains.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Numbers of symptomatic and asymptomatic children at the six sampling time points.
At each sampling time point (from July 2004 to May 2005), the 126 children were grouped into three categories; children with clinical malaria (blood film parasitaemia, fever and at least one other symptom of malaria and no other obvious cause for the fever, described as Symp), children with blood film parasitaemia but no clinical symptoms (Asymp) and children with no blood film parasites (Uninfected).
Fig 2
Fig 2. Antigen-specific antibody level and parasite density variations over the study period.
Levels of either the antigen specific antibodies (A-E) or parasite density (F) at the six sampling time points were compared by the Kruskal-Wallis test, followed by the Bonferroni post-hoc test to assess pair-wise differences. Results (p values) after post-hoc tests are presented in S2 Table.
Fig 3
Fig 3. Pair-wise comparison of AMA1 allele-specific antibody levels.
Points in a panel represent a plot of the fold difference between paired antibody levels (for example, the 3D7-CAMP panel plots the log-transformed anti-3D7 antibody levels minus anti-CAMP antibody levels) in plasma samples against the geometric mean (antilog) of the same paired allele-specific antibody levels. The bold horizontal line (line of equality) in each panel represents the average of all the differences between antibody levels against the specified antigen pair. The dotted horizontal lines represent the 95% limits of agreement for the distribution. Red open circles represent data from children with symptomatic malaria (Symp) and blue open circles are data from children with asymptomatic infections (Asymp).
Fig 4
Fig 4. Comparison of protein sequences (aa25–545) of the for AMA1 antigen variants.
All antigens were produced in Pichia pastoris and devoid of N-glycosylation sites. These have been replaced with amino acid residues (indicated in red) that occur in AMA1 sequences from other Plasmodium parasites (N162K, T288V, S373D, N422D, S423K, N499Q). Each protein consists of a portion of the prodomain (aa25–96), domain I (aa97–315), domain II (aa316–425) and domain III (aa426–545). All antigens reacted with the reduction-sensitive rat monoclonal antibody 4G2 on western blots (Faber et al 2008), which was taken as a surrogate measure of conformational integrity.
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References

    1. World Health Organization: World Malaria Report 2016. Geneva: 2016.
    1. Doolan DL, Dobano C, Baird JK: Acquired Immunity to Malaria. Clinical Microbiology Reviews 2009, 22: 13–36. doi: 10.1128/CMR.00025-08 - DOI - PMC - PubMed
    1. Cohen S, McGregor IA, Carrington S: Gamma-globulin and acquired immunity to human malaria. Nature 1961, 192: 733–737. - PubMed
    1. McGregor IA: The passive transfer of human malarial immunity. Am J Trop Med Hyg 1964, 13: SUPPL-9. - PubMed
    1. Sabchareon A, Burnouf T, Ouattara D, Attanath P, Bouharoun-Tayoun H, Chantavanich P et al.: Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria. Am J Trop Med Hyg 1991, 45: 297–308. - PubMed

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