Mapping evidence on cryptococcal antigen infection among HIV-infected persons in sub-Saharan Africa- A scoping review protocol.

INTRODUCTION: Infections of the central nervous system are a considerable basis of mortality in people living with HIV, with progression to cryptococcal meningitis documented at around 15% of HIV-associated mortality globally, with nearly three-quarters occurring in the sub-Saharan Africa. Discoveries from previous studies prelude to the mortality of cryptococcal antigen positive, which persisted to be elevated than in cryptococcal antigen negative persons. One feasible interpretation of this could be due to undiagnosed cryptococcus. Laboratory investigations identify cryptococcal disease prior to cryptococcal meningitis progression. Point-of-care testing has high sensitivity and specificity as seen with the cryptococcal antigen lateral flow assay screening to expedite treatment. The aim of the study is to map and translate evidence on cryptococcal antigen infection among HIV-infected persons in sub-Saharan Africa. METHODOLOGY: The proposed scoping review will be conducted using guidelines proposed by Arksey and O'Malley methodological framework and Levac et al. advanced method. It will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews. A comprehensive literature search of studies published from the first relevant publication to 2022 will be conducted on multiple electronic databases. Additional sources (grey literature) will also be searched. The search strategy will be generated and implemented by the principal investigator with assistance from a subject specialist, and an information specialist. Two reviewers will screen eligible studies. The screening will be guided by an inclusion and exclusion criteria. The mixed methods appraisal tool version 2018 will be used to appraise the quality of the empirical studies. DISCUSSION: The proposed scoping review will map and translate evidence on cryptococcal antigen infection among HIV-infected persons in sub-Saharan Africa. Synthesising and sharing recent evidence in this area has potential to help guide future research and interventions aimed at improving the management of cryptococcal antigen infection among HIV-infected persons in sub-Saharan Africa and other high HIV- burdened settings.

Plant-produced Bluetongue chimaeric VLP vaccine candidates elicit serotype-specific immunity in sheep.

Bluetongue (BT) is a hemorrhagic non-contagious, biting midge-transmitted disease of wild and domestic ruminants that is caused by bluetongue virus (BTV). Annual vaccination plays a pivotal role in BT disease control in endemic regions. Due to safety concerns of the current BTV multivalent live attenuated vaccine (LAV), a safe efficacious new generation subunit vaccine such as a plant-produced BT virus-like particle (VLP) vaccine is imperative. Previously, homogenous BTV serotype 8 (BTV-8) VLPs were successfully produced in Nicotiana benthamiana plants and provided protective immunity in sheep. In this study, combinations of BTV capsid proteins from more than one serotype were expressed and assembled to form chimaeric BTV-3 and BTV-4 VLPs in N. benthamiana plants. The assembled homogenous BTV-8, as well as chimaeric BTV-3 and chimaeric BTV-4 VLP serotypes, were confirmed by SDS-PAGE, Transmission Electron microscopy (TEM) and protein confirmation using liquid chromatography-mass spectrometry (LC-MS/MS) based peptide sequencing. As VP2 is the major determinant eliciting protective immunity, the percentage coverage and number of unique VP2 peptides detected in assembled chimaeric BT VLPs were used as a guide to assemble the most appropriate chimaeric combinations. Both plant-produced chimaeric BTV-3 and BTV-4 VLPs were able to induce long-lasting serotype-specific neutralizing antibodies equivalent to the monovalent LAV controls. Antibody levels remained high to the end of the trial. Combinations of homogenous and chimaeric BT VLPs have great potential as a safe, effective multivalent vaccine with the ability to distinguish between vaccinated and infected individuals (DIVA) due to the absence of non-structural proteins.