AIDSWEEKLY Plus, April 29, 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

Can a single administration of a peptide-based HIV vaccine induce long-lasting immunity?

Genentech Inc., South San Francisco, California, is betting that the answer is yes.

Chimpanzee studies show that a single shot of the firm's gp120 HIV vaccine can protect chimpanzees against challenge with infectious, heterologous challenge: but only when the challenge is performed just after the animal achieves peak anti-gp120 antibody titers.

"Is it possible to make an AIDS vaccine that elicits high, long-lasting titers so that sterilizing immunity may be achieved several years after immunization?" asked Genentech researcher Michael F. Powell.

Powell described the firm's efforts to answer this question in an address to the International Business Communications (IBC) conference Vaccines: New Technologies and Applications, held February 26-27, 1996, in Rockville, Maryland.

Powell noted that the human immune response to several existing vaccines can indeed be long lasting. In the case of hepatitis B and meningococcal C vaccines, significant residual antibody titers can persist for at least 100 to 120 months after the final vaccination.

In guinea-pig experiments, animals received a single 30 (micro)g dose of gp120 formulated in adjuvant. Anti-gp120 antibody titers initially declined but then persisted at a plateau level for all adjuvants tested (complete Freund's adjuvant, QS-21, MF-59, and alum). The highest plateaus were seen with QS-21 and MF-59.

Similar results were seen when the animals received multiple immunizations, although the plateau levels of persistent antibody were much higher.

This led Powell and colleagues to explore the possibility that encapsulation of gp120 in polymers could provide an "autoboost" that would lead to higher plateau levels of persistent antibody after single-dose immunization.

Guinea-pig experiments showed this response varied according to the formulation of the polylactic coglycolic acid (PLGA) microspheres used for encapsulation. Microspheres formulated to provide a six-month autoboost induced higher plateau antibody levels than microspheres formulated to provide two- or three-month autoboosts.

Subsequent studies showed that the addition of QS-21 adjuvant further increased the anti-gp120 response of guinea pigs to a gp120/polylactic acid (PLA) single-shot vaccine.

In an extension of these studies to a nonhuman primate model, baboons were immunized once with gp120 using different adjuvants.

"Dramatic alteration of antibody decay kinetics with different adjuvants or immunization schedule was observed in baboons, but not in humans," Powell said.

But an approach using a 75:25 ratio of PLA/PLGA gp120 microspheres formulated with QS-21 showed great promise in the baboon model. Animals receiving a single shot of this vaccine had far greater and longer-lasting anti-gp120 responses (about 2.5 log[10] mean antibody titer at 150 days) that animals receiving multiple injections of gp120 in alum (about 1.5 log[10] mean antibody titer at 150 days).

"We found that long-lasting, high antibody titers may be achieved by the sustained release of antigen from PLGA microspheres, especially when combined with added soluble adjuvants in the primary immunization," Powell said.

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.