Combining different types of multifunctional liposomes loaded with ammonium bicarbonate to fabricate microneedle arrays as a vaginal mucosal vaccine adjuvant-dual delivery system (VADDS)
JOURNAL OF CONTROLLED RELEASE
Authors: Wang, Ning; Zhen, Yuanyuan; Jin, Yiguang; Wang, Xueting; Li, Ning; Jiang, Shaohong; Wang, Ting
Abstract
To develop effective mucosal vaccines, two types of multifunctional liposomes, the mannosylated lipid A-liposomes (MLLs) with a size of 200 nm and the stealth lipid A-liposomes (SLLs) of 50 nm, both loaded with a model antigen and NH4HCO3, were fabricated together into microneedles, forming the proSLL/MLL-constituted microneedle array (proSMMA), which upon rehydration dissolved rapidly recovering the initial MLLs and SLLs. Mice vaccinated with proSMMAs by vaginal mucosa patching other than conventional intradermal administration established robust antigen-specific humoral and cellular immunity at both systemic and mucosal levels, especially, in the reproductive and intestinal ducts. Further exploration demonstrated that the MLLs reconstituted from the administered proSMMAs were mostly taken up by vaginal mucosal dendritic cells, whereas the recovered SLLs trafficked directly to draining lymph nodes wherein to be picked up by macrophages. Moreover, the antigens delivered by either liposomes were also cross-presented for MHC-I displaying by APCs thanks to lysosome escape and ROS (reactive oxygen species) stimulation, both of which occurred when lysosomal acidifying the liposome-released NH4HCO3 into CO2 and NH4+/NH3 to rupture lysosomes by gas expansion and to cause ROS production by excessive ammonia induction, resulting in a mixed Th1/Th2 type response which was also promoted by liposomal lipid A via activation of TLR4. In addition, vaginal vaccination of the engineered HSV2 antigen gD-loaded proSMMAs successfully protected mice from the virus challenge. Thus, the proSMMAs are in fact a vaccine adjuvant-dual delivery system capable of eliciting robust humoral and cellular immunity against the invading pathogens, especially, the sexually transmitted ones. (C) 2016 Elsevier B.V. All rights reserved.
Type-specific detection of herpes simplex virus type 1 and type 2 using the cobas (R) HSV 1 and 2 test on the cobas (R) 4800 platform
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
Authors: Van Der Pol, Barbara
Abstract
Introduction: HSV-1 and HSV-2 are among the most common causes of sexually transmitted infections (stis) globally. these infections are strongly associated with increased risk of hiv acquisition and rare, but devastating, neonatal disease. available treatment options can reduce HSV transmission and improve quality of life. accurate diagnosis early in disease can improve patient management.Areas covered: This paper describes the clinical manifestations of HSV infection often used for clinical diagnostic purposes. The paper then describes the evolution of laboratory diagnostic assays. Serology, culture and molecular diagnostics are described since all are currently in use. The features and performance characteristics of the cobas 4800 HSV1 and HSV2 Test (cobas HSV) on the cobas 4800 (R) system (cobas 4800) are described in detail.Expert commentary: Diagnosis of HSV has historically been unreliable or technically difficult, but the availability of molecular assays such as the cobas HSV test for detection and typing of herpes can improve our ability to correctly manage this disease. Utilization of tools such as the cobas HSV assay may help shorten the time to accurate diagnosis and treatment thus potentially reducing the risk of transmission and the global burden of HSV.