Anti-HSV type 2 Polyclonal antibody

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.

Langerhans cells (LC) are dendritic : cells of normal squamous epithelia including skin, oral and genital mucosa. They play a crucial role in immune reactions, especially after viral infections such as human Immune deficiency virus (HIV), papillomaviruses (HPV) and herpes simplex viruses (HSV1 and HSV2). LC are usually identified by their expression of CD1a antigen; they are mainly localized within basal and spinous epithelial layers. Normal mucosa differ from skin by the lack of horney layer and the presence of a high number of T lymphocytes in the epithelium. In human, skin is the preferential site of infection by HSV and by benign HPV types whereas oral and genital mucosa are very sensitive to HIV, HSV and oncogenic HPV types 16 and 18. It is now admitted that HSV and HPV penetrate into the skin through microtrauma whereas the virus route of entry is direct in mucosa. Target cells are epithelial cells for HPV and HSV and T cells for HIV. Epithelial LC can be infected by PIN and HSV and they further transport the complete virus or the virus genome to lymph nodes. Viral infections are responsible of drastic modifications of LC phenotype due to the changes in microenvironment and local production of cytokines fi om epithelial and/or inflammatory cells. For HIV, HSV I-and HPV, memory T cells are essential in controlling persisting infection in the host. LC contribute to the local immune reactions against the infected cells or tumor al cells derived from the infection. Their depletion and their migration into the stroma are common features to HIV, HPV and HSV infections; which may account for a defect of the host immune response to the viruses. Vaccination with LC carrying specific antigens could be an appropriate approach to eliminate infected or tumoral cells derived from these three infections.