AIDSWEEKLY Plus, 01 April 1996 issue; Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588
Daniel J. DeNoon, Senior Editor

The versatile virus-like particle (VLP) produced by the yeast transposon promises to vastly improve particulate antigen vaccines.

Simple monomeric proteins are by themselves only poorly immunogenic. But the creation of particulate, polyvalent antigens permits the elicitation of immune responses without the risks posed by live attenuated pathogens.

In a presentation to the Cambridge Healthtech Institute's Vaccines: New Technologies and Applications conference, held March 18-20, 1996, in McLean, Virginia, researcher Guy Layton of British Biotech Pharmaceuticals Ltd., Oxford, England, summarized the advantages of particulate antigen presentation:

* There is the potential for generic purification instead of the product-specific purification limit of monomeric proteins.

* Polyvalent antigens can be constructed.

* Particulate antigens have a high molecular weight, leading to improved immunogenicity.

* Antigen can be concentrated locally.

* Product-specific purification is possible.

There are many particulate systems currently in development. These include recombinant viral particles; chemical systems such as ISCOMS, liposomes, and microspheres; and yeast transposons (Ty).

Layton provided an overview of research using hybrid yeast transposons to create the Ty-VLPs currently under development by British Biotech.

Thus far the firm has demonstrated that:

* The transposons offer both an external (C-terminal) and internal (Ty p1) cloning site to which antigen-encoding genes can be fused.

* Ty-VLPs prime antibody, T-helper, and cytotoxic lymphocyte (CTL) responses.

* There have been no toxicology issues in Phase I human trials of the HIV p24 Ty-VLP and two hepatitis B VLPs.

* Yields of 1-6 grams of Ty-VLPs can be obtained from a 150- liter fermentation.

* Phase I clinical trials of the p24-VLPs showed them to be safe in humans.

Layton reported the development of a Ty-VLP expressing the highly immunogenic gE envelope glycoprotein of varicella zoster virus, the enveloped alpha herpesvirus that causes chicken pox and herpes zoster.

Mouse studies identified a highly immunogenic fragment of VZV that contains amino acids 101-161 of the gE peptide. Work is underway to further enhance the immunogenicity of this fragment for Phase I clinical trials.

Human trials of the HIV p24 Ty-VLP showed that the vaccine was safe, but it elicited poor CTL responses.

"We are seeing a very different situation in humans than in [preclinical studies] with mice," Layton said. "When I've looked through the primate data, primate responses tend to be weak and transient."

Layton hypothesized that because VLPs quickly migrate to the spleen, measures of CTL responses in the peripheral blood - used in human and non-human primate studies - may have misrepresented the actual effect of the vaccine.

In developing a malaria Ty-VLP, researchers are targeting the sporozoic, pre-erythrocytic stage of the malaria parasite. Five cassettes encoding CTL epitopes are expressed in these Ty-VLPs.

Layton noted that his firm has now made more than 250 Ty- VLP constructions and that both large- and small-scale production is possible.

Copyright (c) 1995 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.

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Copyright © 1996 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.