Optical coherence microscopy for the evaluation of a tissue-engineered artificial cornea

A transparent artificial cornea derived from biological material is the ultimate goal of corneal research. Attempts at artificial corneal constructs produced from synthetic polymers have proved unsuccessful due to lack of biocompatibility and ability to integrate into the tissue. We have designed a corneal model derived from collagenous biological materials that has several advantages: it has low antigenicity and therefore small chance of eliciting an immune reaction, it can be broken down by the body’s own cells and gradually replaced over time by natural materials, and it may contain signaling information for native cells, thereby inducing normal phenotype and behavior. In addition, a transparent corneal model has the potential to be used for testing of novel ophthalmic drugs or gene therapy approaches, eliminating the need for animal testing. We have used an optical coherence microscope (OCM) to evaluate both the structure of our tissue constructs over time in culture and the optical properties of the tissue itself. This imaging technique promises to be an important diagnostic tool in our efforts to understand the influence of mechanical forces, cell phenotype, and soluble factors on the transparency of corneal tissue. From the 26th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society [September 01-05, 2004, San Francisco, CA] IEEE Engn Med & Biol Soc, Whitaker Fdn, Cyberonics, NIH, NIBIB, NIDOCD, NINDS ISBN: 0-7803-8439-

Inhibition of HIV virus by neutralizing Vhh attached to dual functional liposomes encapsulating dapivirine

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high efficacy in reducing viral replication in vitro. Thus, dual function liposomes may lead to a novel strategy for the prophylaxis of HIV/AIDS by combining the neutralizing activity of Vhh with antiviral effects of high drug concentrations

A Neutralizing Monoclonal Antibody Against Poliovirus And Its Reaction With Related Antigens

A neutralizing monoclonal antibody against type 1 poliovirus reacted, not only with native virions (N-antigen) as expected, but also with naturally occurring RNA-free proteins shells (70 S) and with 14 S assembly subunits previously thought to lack N-antigenic sites. The latter finding has important implications for development of subunit vaccines for poliovirus and probably for other picornaviruses as well