As a silent but necessary partner, adjuvants can't be ignored by biotech vaccine developers who have to choose among competing candidates to provide the immune stimulant required to make the vaccines work.

Adjuvant developers Cambridge Biotech Corp. (CBCX), CytRx Corp. (CYTR) and Ribi ImmunoChem Research Inc. (RIBI) are adding proprietary products to the short list of non-proprietary compounds, which they hope become the adjuvants of choice for as many vaccines as possible.

But competition is complicated by the fact that many vaccine companies also are working on their own adjuvants for in-house use. Companies in that category include Chiron Corp. (CHIR), MedImmune Inc. (MEDI) and Genelabs Technologies Inc. (GNLB).

In addition, compounds such as liposomes also have potential as adjuvants. The Liposome Co.'s TLC A-60 is being tested as part of a research collaboration with Merck in an HIV vaccine being developed with Repligen Corp. (RGEN). Wyeth-Ayerst has licensed it for use in an influenza vaccine, which is in advanced preclinical development.

Companies such as Genentech Inc. (GNE) are ranging widely in the search for the best antigen. "We've looked at about a dozen different adjuvants, including QS-21, alum, some polymer-based adjuvants, Freund's and incomplete Freund's," said GNE senior scientist Mike Powell.

(Alum, Freund's water-in-oil emulsion with killed mycobacteria, and incompete Freund's water-in-oil emulsion are in the non-proprietary group.)

GNE is in Phase II trials of its gp120 AIDS vaccine with alum and CBCX's QS-21. Mouse data presented by GNE at the Berlin AIDS conference indicated that QS-21 promoted a better cytotoxic T lymphocyte response than alum. Guinea pig data showed that to produce the same amount of antibody titers, 500- to 1,000-fold less gp120 was needed when using QS-21 versus alum.

Learning from guinea pigs

Other companies have gone inside to produce an effective adjuvant. CHIR developed MF59, an oil and water emulsion (microfluidized squalene), for its own