Multi-epitope chimeric antigen used as a serological marker to estimate Plasmodium falciparum transmission intensity in the border area of China-Myanmar

Abstract

BackgroundFollowing the decline of malaria transmission in many countries and regions, serological parameters have become particularly useful for estimating malaria transmission in low-intensity areas. This study evaluated a novel serological marker, Malaria Random Constructed Antigen-1 (M.RCAg-1), which contains 11 epitopes from eight Plasmodium falciparum antigens, as a tool for assessing malaria transmission intensity along the border area of China-Myanmar.MethodSerum from Plasmodium falciparum and P. vivax patients was used to detect the properties of M.RCAg-1 and antibody responses. Cross-sectional surveys were conducted at the China-Myanmar border and in Hainan province in 2012 and 2013 using cluster sampling. Filter blood spot papers were collected from all participants. Antibodies against M.RCAg-1 were detected using indirect ELISA. The Mann–Whitney test and Spearman’s rank correlation test were performed to analyze antibody data. P. falciparum malaria transmission intensity was estimated using a catalytic conversion model based on the maximum likelihood of generating a community seroconversion rate (SCR).ResultsM.RCAg-1 was well-recognized by the naturally acquired anti-malaria antibodies in P. falciparum patients and had very limited cross-reactivity with P. vivax infection. The total amount of IgG antibodies was decreased with the decrease in parasitemia after taking medication and lasted several weeks. In a population survey, the antibody levels were higher in residents living close to the China-Myanmar border than those living in non-epidemic areas (P < 0.0001), but no significant difference was observed between residents from Hainan and non-epidemic areas. The calculated SCR was 0.0128 for Jieyangka, 0.004 for Susuzhai, 0.0047 for Qiushan, and 0.043 for Kayahe. The estimated exposure rate obtained from the anti-M.RCAg-1 antibody level correlated with traditional measures of transmission intensity derived from altitude.ConclusionOur study demonstrates that M.RCAg-1 is potentially useful as a serological indicator of exposure to P. falciparum malaria, especially for malaria surveillance in low transmission areas.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-016-0194-x) contains supplementary material, which is available to authorized users.

Natural Infections With Different Plasmodium Species Induce Antibodies Reactive to A Chimeric Plasmodium Vivax Recombinant Protein

“…For malaria serological studies, tailoring the sensitivity of the assay using a highly antigenic protein has previously been suggested as a method to improve serological testing and the estimates generated by this data (8). A recent assessment of a multi-epitope chimeric protein for use as a serological marker in P. falciparum elimination settings in Southeast Asia demonstrated the potential of chimeric proteins in serological studies (25). Another protein chimera based on the fusion of the P. falciparum MSP1 and MSP8 antigens has shown e cacy for the induction of growth-inhibitory antibodies in animal models (36,37), but has been yet to be assayed against human plasma from naturally-exposed populations.…”

“…The addition of pan-malaria antigens for IgG detection could improve malaria exposure estimates to aid in malaria elimination campaigns, which aim to eliminate all malaria transmission within a region, not just an individual species. Recently, the use of designed chimeric Plasmodium proteins as serosurveillance tools has been explored, including a multi-epitope chimeric antigen that contained epitopes from eight P. falciparum antigens (25,26). While this antigen was wellrecognized by P. falciparum-infected individuals in endemic regions along the China-Myanmar border, it displayed limited cross-reactivity with P. vivax-infected individuals (25).…”

Comparative Analysis of the Serological Reactivity of Individuals with Clinical History of Malaria using Two Different ELISA Tests

“…It is important to remember that many antigens present in the pre-erythrocyte and erythrocyte stages play important roles in the protection against malaria [3,27,28]. Several studies have been carried out on the functionality of P. falciparum antigens in diagnosis and it has been found, for example, that MRCAg1 chimeric antigen, containing eight epitopes of P. falciparum, is a potential marker for the detection of malaria caused by P. falciparum [29][30][31]. In addition, some studies have been conducted to understand the antibody response against malaria infection using ELISA [2,3], suggesting that ELISA is a good method for evaluating the humoral immune response.…”

malERA: An updated research agenda for characterising the reservoir and measuring transmission in malaria elimination and eradication

“…vivax [ 88 ], serological signatures of hypnozoite carriage [ 92 ], and vector-specific antigenic targets in mosquito saliva [ 93 , 94 ]. The programmatic applications of serology have yet to be fully tested, though various approaches are being evaluated, including serological markers of incident infections [ 89 , 95 – 109 ]. Research is currently underway to identify a variety of biomarkers indicative of recent infection that are detectable for different durations following parasite infection, allowing finer-scale estimation of time since infection.…”