Cochleate Delivery Vehicles: Applications in Vaccine Delivery

Abstract

Cochleates represent a powerful subunit vaccine delivery system, uniquely suited to meeting the challenges of modern vaccine development. The intrinsic properties of cochleates lead to advantages in the important areas of safety, stability, efficacy, immune response targeting, combining vaccines to multiple infectious agents, alternate routes of administration (including oral and intranasal), and the generation of mucosal immunity. Cochleates are alternating layers of cations and negatively charged lipids, in stacked sheets 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 current study investigated the relative amounts of the different classes and subtypes of antibodies generated in mice in response to the oral administration of influenza glycoprotein cochleates. Analysis of circulating antibody revealed significant levels of flu glycoprotein-specific IgG, IgM, and IgA class, and IgGI and IgG2a subtype, antibodies. Oral administration of influenza glycoprotein cochleates also induced antigen-specific salivary IgA levels. The immune responses induced were protective against infection in the respiratory tract following intranasal challenge with live influenza virus. DNA plasmids and oligonucleotides can also be formulated into cochleates. Cochleates containing a plasmid that expresses the human immunodeficiency virus, (HIV-1), proteins env (gp160), rev, and tat, in mammalian cells, was given to mice orally or by intramuscular injection. Two oral administrations yielded strong splenocyte cytolytic and proliferative responses. These cellular responses were essentially the same as those obtained by analogous intramuscular injection of DNA cochleates. Very small quantities of encochleated DNA were required to induce these responses, whereas a higher dose of naked DNA given orally induced no cytotoxic or proliferative responses. Cochleates containing pathogen proteins or DNA, formulated, adjuvanted, and delivered in a variety of ways, represent powerful tools for dissecting and directing the immune response to complex pathogens. The ability of cochleates to induce antibody and cell mediated responses, systemically and on mucosal surfaces, makes them desirable candidates for development of preventive and therapeutic vaccines.

Keywords::

• Cochleate
• DNA vaccines
• Influenza
• Oral administration
• Mucosal immunity