Antibodies from dengue patients with prior exposure to Japanese encephalitis virus are broadly neutralizing against Zika virus.

Exposure to multiple mosquito-borne flaviviruses within a lifetime is not uncommon; however, how sequential exposures to different flaviviruses shape the cross-reactive humoral response against an antigen from a different serocomplex has yet to be explored. Here, we report that dengue-infected individuals initially primed with the Japanese encephalitis virus (JEV) showed broad, highly neutralizing potencies against Zika virus (ZIKV). We also identified a rare class of ZIKV-cross-reactive human monoclonal antibodies with increased somatic hypermutation and broad neutralization against multiple flaviviruses. One huMAb, K8b, binds quaternary epitopes with heavy and light chains separately interacting with overlapping envelope protein dimer units spanning domains I, II, and III through cryo-electron microscopy and structure-based mutagenesis. JEV virus-like particle immunization in mice further confirmed that such cross-reactive antibodies, mainly IgG3 isotype, can be induced and proliferate through heterologous dengue virus (DENV) serotype 2 virus-like particle stimulation. Our findings highlight the role of prior immunity in JEV and DENV in shaping the breadth of humoral response and provide insights for future vaccination strategies in flavivirus-endemic countries.

Evaluation of loop-mediated isothermal amplification assay and enzyme-linked immunosorbent assay in detecting Schistosoma japonicum in Siargao Island, Surigao del Norte, the Philippines.

OBJECTIVES: This study aimed to describe the prevalence and seroprevalence of schistosomiasis in Siargao Island, Surigao del Norte and to compare the performance of enzyme-linked immunosorbent assay antibody test (ELISA Ab) and loop-mediated isothermal amplification assay (LAMP) for diagnosis of schistosomiasis. METHODS: The study was conducted in selected barangays (villages) in five municipalities in Siargao Island, Surigao del Norte and included school-age children (SAC) who submitted stool and blood samples. Stool samples were examined using the Kato-Katz technique. Blood samples were collected through venipuncture. The stool samples and the blood samples collected were tested using LAMP assay and polymerase chain reaction (PCR). The blood samples were examined using ELISA Ab. Diagnostic performance of LAMP assay using stool specimen was evaluated using Kato-Katz technique and PCR assay as the composite reference standard, while PCR assay was used as the reference standard to evaluate LAMP assay and ELISA Ab using blood specimens. RESULTS: A total of 417 stool samples from SAC were examined. The prevalence of schistosomiasis and moderate-heavy intensity (MHI) schistosomiasis were 3.8% and 1.4%, respectively. Schistosomiasis and soil-transmitted helminthiases (STH) coinfection prevalence were 2.6%. A total of 425 blood samples were examined using ELISA Ab. Seroprevalence was 61.6%. The municipality of San Isidro had the highest seroprevalence at 84.8%, while Burgos had the lowest seroprevalence at 48.5%.LAMP assay had higher sensitivity and positive predictive value but lower specificity when using stool than when using blood samples. Its negative predictive value was similar regardless of the specimen used. ELISA Ab has higher sensitivity and negative predictive value than LAMP assay although it has lower specificity and positive predictive value. This may be due to ELISA Ab measuring Schistosoma exposure and is thus unable to distinguish past from active infection. CONCLUSIONS: Schistosomiasis remains a public health concern in Siargao Island, Surigao del Norte. The locally developed LAMP assay offers a simpler diagnostic test for schistosomiasis compared with PCR, while minimizing the risk of misdiagnosis compared with Kato-Katz technique. It could serve as a point of care diagnostics for schistosomiasis. ELISA Ab is more useful in surveillance particularly in low-endemicity areas where determination of exposure is more important than differentiating past from active infection. ELISA Ab may be helpful in the clinical setting when coupled with the expertise of a physician who is familiar with schistosomiasis.