Abstract
Plasmodium vivax remains an important cause of malaria in South America and the Asia-Pacific. Naturally acquired antibody responses against multiple P. vivax proteins have been described in numerous countries, however, direct comparison of these responses has been difficult with different methodologies employed. We measured antibody responses against 307 P. vivax proteins at the time of P. vivax infection, and at 2–3 later time-points in three countries. We observed that seropositivity rates at the time of infection were highest in Thailand, followed by Brazil then PNG, reflecting the level of antigenic input. The majority of sero-reactive antigens in all sites induced short-lived antibody responses with estimated half-lives of less than 6 months, although there was a trend towards longer-lived responses in PNG children. Despite these differences, IgG seropositivity rates, magnitude and longevity were highly and significantly rank-correlated between the different regions, suggesting such features are reflective of the individual protein.
Highlights
Plasmodium vivax is the most geographically widespread of the Plasmodium spp. causing malaria in humans, and accounts for the majority of cases outside Africa [1]
All Thai and Brazilian volunteers were enrolled following symptomatic infection, whilst all included Papua New Guinea (PNG) children had asymptomatic infections. This resulted in significantly higher antigenic inputs in the Thai and Brazilian volunteers compared to PNG children (p
At the time of P. vivax infection we observed that a high proportion of the 307 P. vivax proteins were reactive (77–98%)
Summary
Plasmodium vivax is the most geographically widespread of the Plasmodium spp. causing malaria in humans, and accounts for the majority of cases outside Africa [1]. Interrupting P. vivax transmission may require the development of an effective vaccine and improved surveillance systems (due to the high proportion of sub-microscopic P. vivax infections [4] and the presence of currently undetectable hypnozoites) [5] Both objectives require a better understanding of naturally induced immune responses, in particular antibody responses, following infection. The parasite expresses more than 5000 proteins throughout its lifecycle [15], and through the use of large-scale screening platforms such as protein microarrays [16], an increasing number of these proteins have been assessed for their immunogenicity in naturally exposed populations These studies, assessing antibody responses to over 1900 P. vivax proteins, have indicated that up to 50% of such proteins are sero-reactive in individuals from malaria endemic areas [11]. They have demonstrated that asymptomatic individuals have a greater breadth of response [11], that reactive proteins are more likely to be encoded by genes with high single nucleotide polymorphism diversity (potentially signifying positive immune selection) [17], and that the majority of highly reactive proteins have predicted transmembrane domains and signal peptides (SP) (signifying secreted or membrane-bound proteins) [18]
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