AIDSWEEKLY Plus, 11 March 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

Nature has provided an answer to a key question in vaccinology: how to stimulate killer T cells with small- peptide-based vaccines.

The answer may be of immediate use in the development of HIV vaccines, as cell-mediated immunity appears crucial to control of the AIDS virus. But the finding may apply to other viral and parasitic diseases as well.

Although vaccines based on synthetic peptides are safe and relatively easy to produce, they generally fail to elicit cytotoxic lymphocytes (CTL) because exogenous peptides are processed by the major histocompatibility complex type II (MHC-II) pathway - leading to CD4(+) T-lymphocyte-mediated immune responses and antibody production - rather than the MHC-I pathway, leading to CD8(+) T-lymphocyte-mediated immune responses and CTL activation.

"Nature potentially left the window open a little bit where one could get a protein into the MHC-I pathway," said Kenneth L. Rock of the Dana-Farber Cancer Institute, Boston, Massachusetts.

Rock announced his discovery at the Eighth Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS (NCVDG), held February 11-15, 1996, in Bethesda, Maryland.

During in vitro studies of the segregation of the MHC-I and MHC-II pathways, Rock observed that in some situations proteins were able to elicit MHC-I responses.

He found that phagocytes - cells capable of ingesting and degrading bacteria, foreign particles, and other cells - can present exogenous protein antigens on their class I molecules.

"This pathway may have evolved to deal with infections of phagocytes or pathogens that infect some somatic cells," Rock hypothesized.

By targeting peptides to phagocytes, Rock suggested, vaccine developers could take advantage of this natural pathway.

Indeed, in preliminary experiments he found that microscopic beads - one to four microns appeared to be the optimal size - could be coated with peptides and used to stimulate CTL in mice lacking CD4 cells.

"Priming of CTL with HIV gp120 [envelope glycoprotein]- coated beads generated gp120-specific CTL in mice," Rock reported.

Rock and co-workers continue to experiment on the optimal design of the peptide-carrying beads. They began with beads made of iron oxide or latex, but have more recently been experimenting with polylactide-based technology.

"We haven't fully resolved all problems," Rock noted.

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.