Naturally acquired IgG antibodies to thrombospondin-related anonymous protein of P. vivax in Thailand predominantly elicit immunological cross-reactivity

BACKGROUND

Thrombospondin-related anonymous protein (TRAP) is a prime candidate for a malaria vaccine. Antibodies to Plasmodium vivax TRAP (PvTRAP) occur upon natural infection while specific antigenic domains remain to be addressed.

METHODS

The PvTRAP sequences were determined from 73 P. vivax isolates from Tak and Ubon Ratchathani provinces collected in 2013. The recombinant proteins representing four variants each for domain II (A domain) and domain IV (thrombospondin repeat region) of PvTRAP circulating in these areas were used as antigens in enzyme-linked immunosorbent assay against 246 serum samples from P. vivax-infected patients in both provinces collected during 2013 and 2014.

RESULTS

The prevalence of total IgG antibodies to at least one variant antigen of domain II and domain IV was 63.8% and 71.5%, respectively. Differential IgG antibody responses to these variant antigens of each domain were observed. Total IgG antibody responses to the variant antigens of each domain upon pairwise comparisons were highly correlated, suggesting immunological cross-reactivity in the majority of serum samples. A smaller proportion of serum samples contained non-cross-reactive antibodies to variants of each domain; particularly domain II in which amino acid differences significantly influenced antibody recognition. Previous malaria exposure positively affected antibody responses to domain IV. Positive seroconversion and rising antibody titres occurred within a few weeks after resolution of infections.

CONCLUSIONS

Both domains II and IV are targets of naturally acquired IgG antibodies. Despite sequence variation in these domains, most antibody responses were cross-reactive. A cross-sectional evaluation of antibodies to PvTRAP during acute infection could underestimate the seroprevalence.