[Memorandum to Presidential Advisory Council on HIV and AIDS Research Committee Members from Bruce G. Weniger]

FROM ' OPRAqGEN

PHONE NO.: 01483 560074

JTan. 06 199"? 11:21PM PO4

2. The Vaccines
There are potentially four approaches to a vaccine protective against the disease of AIDS
based on our current knowledge of what constitutes a successful virus vaccine. These
are: the whole or part of a killed pathogenic virus; a live attenuated virus; virus-like
particles and, if the DNA based influenza vaccine works, plasmid DNA. Each such
vaccine type may be manifested in a multitude of actual forms.
3. The Components of a Vaccine Discovery and Development System.
The development, production and evaluation of a virus vaccine requires a suite of
facilities into which the various vaccine options can be plugged. Such a suite may
consist of the following elements:
* an epidemiology unit
* a virus identification unit
* a virus assay unit (by several methods to give viability as well as quantity)
* a virus production unit at the laboratory scale (requires an associated utility
which can produce the cell culture systems in which the virus can be
grown)
* a virus production facility at the pilot plant scale (c. 1001itrc reactors) for
the production of test lots of vaccine at putative commercial scales of
operation)
* a virus purification unil
* a vaccine formulation unit
* n vaccine assay unit using;
physicochemical assays for mass, antigenicity, heterogeneity
cell culture assays for in vitro neutralisation on more than one cell
line
immune cell assays in vitro (antibody and/or CTL response)
small animal assays which for HIV can be sensitised mice (SCID)
small primate assays
large primate assays
target animal assays (humans who are infected; humans who are not
infected)
* a biochemical unit to provide characterization data based on now and
innovative assay systems; this unit may also generate putative vaccine
materials, provide understanding on the way inactivation mechanisms
work, examine the stability of the virus and the way it is modified
immunogenically when formulated as a vaccine and examine at the
biochemical level aspects of virus pathogenesis
* a pathogenesis unit to examine at the organismal and cellular level the life
history of the virus and the way it causes disease
* a genetics unit to provide information on genetic changes to the virus and
their implications for the production of an effective vaccine

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