Immunoglobulin E (IgE) Responses to Paramyosin Predict Resistance to Reinfection withSchistosoma japonicumand Are Attenuated by IgG4

Abstract

Schistosomiasis remains a public health concern in developing countries, and rapid reinfection fostered by continued exposure to contaminated water sources necessitates a vaccine to augment current mass treatmentbased control strategies. We report isotype-specific (immunoglobulin A [IgA], IgE, IgG1, IgG4, and IgG) antibody responses to soluble worm antigen preparation and the recombinant vaccine candidates rSj97, rSj67, and rSj22 from a Schistosoma japonicum-infected cohort in Leyte, the Philippines, where schistosomiasis is endemic. Sera were collected from infected individuals 1 month posttreatment with praziquantel, and antibody responses were measured using a bead-based multiplex platform. Reinfection was monitored by stool sampling every 3 months, and data up to 1 year were included in the analysis (n ‫؍‬ 553). In repeated-measures models, individuals with detectible IgE responses to rSj97 had a 26% lower intensity of reinfection at 12 months posttreatment compared to nonresponders after adjusting for age, gender, village, exposure, pretreatment infection intensity, and clustering by household (P ‫؍‬ 0.018). In contrast, IgG4 responses to rSj97 as well as rSj67 and rSj22 were associated with markedly increased reinfection intensity. When stratified by IgG4 and IgE responder status, individuals with IgE but not IgG4 responses to rSj97 (n ‫؍‬ 16) had a 77% lower intensity of reinfection at 12 months compared to individuals with IgG4 responses but not IgE responses (n ‫؍‬ 274), even after adjusting for potential confounders (P ‫؍‬ 0.016). Together with our previously described protective cytokine responses, these data further support paramyosin as a leading vaccine candidate for human schistosomiasis japonica and underscore the importance of careful adjuvant selection to avoid the generation of blocking IgG4 antibody responses.

Efficacy and Safety of Arachidonic Acid for Treatment of Schistosoma mansoni-Infected Children in Menoufiya, Egypt

“…50 More importantly, ARA-associated significant decreases of the levels of the immunosuppressive IL-10 and the Th1 cytokine IFN-γ may enhance development and polarization of Th2-related immune responses to parasite antigens, which could lead to a prognosis of resistance to reinfection with schistosomes. 51,52 The results taken together urge additional validating studies, because if ARA effectiveness against light S. mansoni infections is confirmed, then it may be used instead of PZQ for travelers coming from endemic regions who show signs of infection and poor, malnourished children in areas with low endemicity. For moderate and heavy infections, it might be recommended to use ARA in conjunction with PZQ to decrease to a minimum the percentage of children still harboring worms and living usually unaware of the danger of persisting infection.…”

CD23-Bound IgE Augments and Dominates Recall Responses through Human Naive B Cells

“…This is best illustrated in age-acquired immunity where young children demonstrate susceptibility to infection/reinfection, heavy parasite burden, and low levels of schistosome-specific IgE (32). Resistance begins to develop around the time of puberty onset when schistosome-specific IgE is apparent (33,34), but the mechanisms remain unclear and are the subject of debate (35,36).…”

Effects of Treatment on IgE Responses against Parasite Allergen-Like Proteins and Immunity to Reinfection in Childhood Schistosome and Hookworm Coinfections

“…In both helminth infections, IgE responses to a number of defined antigens are strongly associated with immunity (5,15,16), and many of these antigens share structural homology with allergens (17). For example, IgE to Schistosoma mansoni tegumental-allergen-like 1 protein (SmTAL1-IgE) is a marker for human immunity in schistosomiasis mansoni (5,16); SmTAL1 is a member of the TAL family, a group of proteins sharing structural homology with the EF hand allergens, one of the most common groups of clinical allergens (9).…”