Enterovirus specific anti-peptide antibodies

Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically. The high cost of manufacturing and supply problems may limit practical implementations in developing countries. Synthetic peptides representing the native primary structure of the viral immunogen which is able to elicit neutralizing antibodies can be made readily and is cost effective. However, it is necessary to conjugate short synthetic peptides to carrier proteins to enhance their immunogenicity. This review describes the production of cross-neutralizing anti-peptide antibodies in response to immunization with synthetic peptides selected from in silico analysis, generation of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from Poliovirus, and evaluation of the neutralizing activities of the anti-peptide antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and ECHO13

The P2X1 receptor and platelet function

Extracellular nucleotides are ubiquitous signalling molecules, acting via the P2 class of surface receptors. Platelets express three P2 receptor subtypes, ADP-dependent P2Y1 and P2Y12 G-protein-coupled receptors and the ATP-gated P2X1 non-selective cation channel. Platelet P2X1 receptors can generate significant increases in intracellular Ca2+, leading to shape change, movement of secretory granules and low levels of αIIbβ3 integrin activation. P2X1 can also synergise with several other receptors to amplify signalling and functional events in the platelet. In particular, activation of P2X1 receptors by ATP released from dense granules amplifies the aggregation responses to low levels of the major agonists, collagen and thrombin. In vivo studies using transgenic murine models show that P2X1 receptors amplify localised thrombosis following damage of small arteries and arterioles and also contribute to thromboembolism induced by intravenous co-injection of collagen and adrenaline. In vitro, under flow conditions, P2X1 receptors contribute more to aggregate formation on collagen-coated surfaces as the shear rate is increased, which may explain their greater contribution to localised thrombosis in arterioles compared to venules within in vivo models. Since shear increases substantially near sites of stenosis, anti-P2X1 therapy represents a potential means of reducing thrombotic events at atherosclerotic plaques

Treatment options for the eradication of intestinal protozoa

Pathogenic intestinal protozoa are responsible for clinically important infections in both the developed and the developing world. These organisms are responsible for both acute and chronic diarrhea, and Entamoeba histolytica, which affects the colon, can spread to involve the liver. Many of these pathogens, particularly the intracellular protozoa that predominantly affect the small intestine, produce their most devastating effects in patients with HIV/AIDS and other forms of immune deficiency. There are also various intestinal protozoa that do not seem to have any adverse effects on humans and can, therefore, be regarded as harmless commensal organisms. Although treatment has been available for several decades for giardiasis, isosporiasis and amoebiasis, until recently there have been no effective remedies for infection with intestinal coccidia—Cryptosporidium, Microsporidium and Cyclospora species. Cyclospora respond well to co-trimoxazole, microsporidia respond variably to albendazole, and cryptosporidia can often be eradicated by nitazoxanide. In chronically infected HIV-positive patients, treatment with multidrug regimens usually results in rapid resolution of the diarrhea and, in many instances, eradication of the parasite