Cochleate delivery vehicles: Applications in vaccine delivery

Cochleates represent a powerful subunit vaccine delivery system, uniquely s uited to meeting the challenges of modern vaccine development. The intrinsi c properties of cochleates lead to advantages in the important areas of saf ety, stability, efficacy, immune response targeting, combining vaccines to multiple infectious agents, alternate routes of administration (including o ral and intranasal), and the generation of mucosal immunity. Cochleates are alternating layers of cations and negatively charged lipids, in stacked sh eets or rolled scrolls, with little or no internal aqueous space. Bacterial membrane proteins or the surface glycoproteins of enveloped viruses can be efficiently integrated into the lipid bilayers of the cochleates. The curr ent study investigated the relative amounts of the different classes and su btypes of antibodies generated in mice in response to the oral administrati on of influenza glycoprotein cochleates. Analysis of circulating antibody r evealed significant levels of flu glycoprotein-specific IgG, IgM, and IgA c lass, and IgG1 and IgG2a subtype, antibodies. Oral-administration of influe nza glycoprotein cochleates also induced antigen-specific salivary IgA leve ls. The immune responses induced were protective against infection in the r espiratory tract following intranasal challenge with live influenza virus. DNA plasmids and oligonucleotides can also be formulated into cochleates. C ochleates containing a plasmid that expresses the human immunodeficiency vi rus, (HIV-1), proteins env (gp160), rev, and tat, in mammalian cells, was g iven to mice orally or by intramuscular injection. Two oral administrations yielded strong splenocyte cytolytic and proliferative responses. These cel lular responses were essentially the same as those obtained by analogous in tramuscular injection of DNA cochleates. Very small quantities of encochlea ted DNA were required to induce these responses, whereas a higher dose of n aked DNA given orally induced no cytotoxic or proliferative responses. Coch leates containing pathogen proteins or DNA, formulated, adjuvanted, and del ivered in a variety of ways, represent powerful tools for dissecting and di recting the immune response to complex pathogens. The ability of cochleates to induce antibody and cell mediated responses, systemically and on mucosa l surfaces, makes them desirable candidates for development of preventive a nd therapeutic vaccines.