Plasmodium falciparum Cysteine-Rich Protective Antigen (CyRPA) Elicits Detectable Levels of Invasion-Inhibitory Antibodies during Natural Infection in Humans.

Plasmodium falciparum cysteine-rich protective antigen (CyRPA) is a conserved component of an essential erythrocyte invasion complex (RH5/Ripr/CyRPA) and a target of potent cross-strain parasite-neutralizing antibodies. While naturally acquired human RH5 antibodies have been functionally characterized, there are no similar reports on CyRPA. Thus, we analyzed the parasite-neutralizing activity of naturally acquired human CyRPA antibodies. In this regard, CyRPA human antibodies were measured and purified from malaria-infected plasma obtained from patients in central India and analyzed for their parasite neutralizing activity via in vitro growth inhibition assays (GIA). We report that, despite being susceptible to antibodies, CyRPA is a highly conserved antigen that does not appear to be under substantial immune selection pressure, as a very low acquisition rate for anti-CyRPA antibodies was reported in malaria-exposed Indians. We demonstrate for the first time that the small amounts of natural CyRPA antibodies exhibited functional parasite-neutralizing activity and that a CyRPA-based vaccine formulation induces highly potent antibodies in rabbits. Importantly, the vaccine-induced CyRPA antibodies exhibited a robust 50% inhibitory concentration (IC50) of 21.96 µg/ml, which is comparable to the IC50 of antibodies against the leading blood-stage vaccine candidate, reticulocyte-binding-like homologous protein 5 (RH5). Our data support CyRPA as a unique vaccine target that is highly susceptible to immune attack but is highly conserved compared to other leading candidates such as MSP-1 and AMA-1, further substantiating its promise as a leading blood-stage vaccine candidate.

Systemic Associations of Childhood Glaucoma: A Review.

PURPOSE: To review systemic associations of childhood glaucoma. METHODS: Patients younger than 15 years and diagnosed as having glaucoma were divided into four groups: isolated primary congenital glaucoma, glaucoma with other congenital ocular anomalies, congenital glaucoma with known systemic diseases, and secondary glaucoma. Prevalence and type of systemic associations in each group were studied. RESULTS: A retrospective analysis of 371 patients diagnosed as having glaucoma was done. In the primary congenital glaucoma group, 13 of 218 (5.9%) patients had an associated systemic illness: congenital heart disease and global developmental delay were the most common systemic manifestations. In the congenital ocular anomalies group, 10 of 63 (15.8%) patients had an associated systemic illness. Axenfeld-Reiger syndrome, aniridia, and Peters' anomaly frequently had systemic comorbidities with congenital heart disease. In the known systemic diseases group, all 18 (100%) patients had systemic manifestations of an associated syndrome: Sturge-Weber and Down syndrome were the most frequent. In the secondary glaucoma group, 9 of 72 (12.5%) patients had systemic involvement, which was often seen as the most common cause after congenital cataract surgery. These children had congenital heart disease and global developmental delay as a consequence of congenital rubella and congenital cytomegalovirus infection. CONCLUSIONS: The study found that 12.9% of patients with childhood glaucoma had an associated systemic abnormality. Patients with congenital glaucoma and other ocular anomalies have a three times higher risk of an underlying systemic anomaly than patients with isolated primary congenital glaucoma. A team comprising an ophthalmologist, pediatrician, and anesthesiologist is recommended to treat these cases. [J Pediatr Ophthalmol Strabismus. 2018;55(6):397-402.].