The following summary article describes recent research by IMNR personel on the production processs for Remune. The search was obtained through the Bio-medical Library. I have not seen any press releases describing this research. It is important, because quality control in the production process would be the next logical concern of FDA if Phase III data indicate efficacy.
Accession Number
YL616-0002
Authors
Richieri SP
Bartholomew R
Aloia RC
Savary J
Gore R
Holt J
Ferre F
Musil R
Tian HR
Trauger R
Lowry P
Jensen F
Carlo DJ
Maigetter RZ
Prior CP
Title
CHARACTERIZATION OF HIGHLY PURIFIED, INACTIVATED HIV-1 PARTICLES ISOLATED
BY ANION EXCHANGE CHROMATOGRAPHY
Source
Vaccine. 16(2-3):119-129, 1998 Jan-Feb.
Author Keywords
Human immunodeficiency virus (hiv-1). Gp120 depleted. Anion exchange
purified. Protein, lipid, carbohydrate and rna composition.
KeyWords Plus
Human-immunodeficiency-virus. Lipid-composition. Proteins.
Purification. Pathogenesis. Infection. Fluidity. Type-1. Gag.
Abstract
This report characterizes inactivated, gp120 depleted, HIV-1 particles
purified by an anion exchange chromatography production process. This
antigen formulated with incomplete Freund's adjuvant constitutes
Remune(TM), which is being evaluated in a phase III clinical endpoint
trial to determine the effect of this immune-based therapy on clinical
progression of HIV-1 seropositive patients. Multiple production lots of
the inactivated HN-I antigen strain HZ321, isolated by anion exchange
chromatography, exhibit purity of > 95% by gel filtration. These findings
are corroborated by thin section electron microscopy showing a homogenous
field of intact particles. Analyses of the purified virus par-tides for
protein, lipid, carbohydrate and RNA show structural retention of the
envelope proteins, lipid bilayer and core components after large scale
processing. The qualitative identification of at least 85% of total HIV-1
protein is determined by ELISA, Western blot HPLC and amino acid
sequencing analyses. Quantitative values are assigned to 50% of these
proteins. The data confirm the presence of virally encoded proteins p6,
p7, p(1)15, p17, p24, p32, p(1)39(Gag), gp41, p(p)55(Gag), p66/51, Vpr;
Vif and Nef: Excellent consistency between production lots and equivalency
to HN-I preparations purified by sucrose density gradient sedimentation
has been established for protein and lipid composition, and overall
purity. These findings further establish that non-viral encoded proteins
and lipids are integral structural components of the intact virion and are
not contaminants unique to a particular isolation method. The data confirm
the presence of multicomponent antigens in the viral particles for
stimulating a broad HIV-1 specific immune response. Finally, the work
demonstrates that the two inactivation procedures (beta-propiolactone and
gamma irradiation), which achieve efficient viral inactivation meeting US
FDA guidelines, do not damage the protein antigens of the viral particles.
(C) 1997 Elsevier Science Ltd. All rights reserved. [References: 26] |
