Antibody responses to the full-length VAR2CSA and its DBL domains in Cameroonian children and teenagers

Abstract

BackgroundAntigenic variation of Plasmodium falciparum erythrocyte membrane protein 1 is a key parasite mechanism for immune evasion and parasite survival. It is assumed that the number of parasites expressing the same var gene must reach high enough numbers before the host can produce detectable levels of antibodies (Ab) to the variant. VAR2CSA is a protein coded for by one of 60 var genes that is expressed on the surface of infected erythrocytes (IE) and mediates IE binding to the placenta. The idea that Ab to VAR2CSA are pregnancy-associated was challenged when VAR2CSA-specific Ab were reported in children and men. However, the frequency and conditions under which Ab to VAR2CSA are produced outside pregnancy is unclear. This study sought to determine frequency, specificity and level of Ab to VAR2CSA produced in children and whether children with hyperparasitaemia and severe malaria are more likely to produce Ab to VAR2CSA compared to healthy children.MethodsAntibody responses to a panel of recombinant proteins consisting of multiple VAR2CSA Duffy-binding-like domains (DBL) and full-length VAR2CSA (FV2) were characterized in 193 1–15 year old children from rural Cameroonian villages and 160 children with severe malaria from the city.ResultsLow Ab levels to VAR2CSA were detected in children; however, Ab levels to FV2 in teenagers were rare. Children preferentially recognized DBL2 (56–70%) and DBL4 (50–60%), while multigravidae produced high levels of IgG to DBL3, DBL5 and FV2. Sixty-seven percent of teenage girls (n = 16/24) recognized ID1–ID2a region of VAR2CSA. Children with severe forms of malaria had significantly higher IgG to merozoite antigens (all p < 0.05), but not to VAR2CSA (all p > 0.05) when compared to the healthy children.ConclusionThe study suggests that children, including teenage girls acquire Ab to VAR2CSA domains and FV2, but Ab levels are much lower than those needed to protect women from placental infections and repertoire of Ab responses to DBL domains is different from those in pregnant women. Interestingly, children with severe malaria did not have higher Ab levels to VAR2CSA compared to healthy children.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1585-y) contains supplementary material, which is available to authorized users.

Comparative analysis of IgG and IgG subclasses against Plasmodium falciparum MSP-119 in children from five contrasting bioecological zones of Cameroon

“…This is also evident from the finding of only P. falciparum as the cause of clinical malaria in the target population. In this study, the levels of all the IgG subclasses increased with age overall, which corroborates the findings of other studies performed in Cameroon [39, 40]. This could be attributed to the increasing number of exposure to malaria parasite infection with age.…”

PRIMVAC vaccine adjuvanted with Alhydrogel or GLA-SE to prevent placental malaria: a first-in-human, randomised, double-blind, placebo-controlled study

“…Field studies have previously reported low levels of anti-VAR2CSA antibodies in children, men and teenage girls. [25][26][27] Therefore, antibodies to VAR2CSA seems to be acquired, to some extent, outside of the pregnancy context. This could be the consequence of prior exposure to VAR2CSA or to malaria antigens sharing common epitopes with VAR2CSA such as other PfEMP1 or P. vivax Duffy Binding Protein (PvDBP).…”

“…A total of 338 AE and 186 adverse events following immunization (AEFI) related to the vaccine were documented (Table 2 and Table S3; appendix pp 12-13). For the cohort A (n=6), 54 AE were reported, 45 related to the vaccine: 25 Table 3).…”

IgG Responses to the Plasmodium falciparum Antigen VAR2CSA in Colombia Are Restricted to Pregnancy and Are Not Induced by Exposure to Plasmodium vivax

“…The expression of VAR2CSA is generally assumed to be incompatible with parasite survival in nonpregnant individuals ( 6 , 8 ). Therefore, the acquisition of VAR2CSA-specific IgG is normally regarded as being pregnancy restricted, despite a few reports of sporadic, low levels of VAR2CSA-specific IgG among P. falciparum -exposed men, children, and nulligravidae ( 9 – 12 ).…”