Production of antibodies to HIV

Details Production of antibodies to HIV Production of antibodies to HIV

1988-01-21

1991-05-07

Moezie, F. T.

Drug, bio-affecting and body treating compositions

Lymphokine

424 855, 424 858, 530324, 530325, 530326, 530327, 530328, 530387, 530388, A61K 3912, A61K 3702

Patent

active

050135481

DESCRIPTION:

BRIEF SUMMARY
e above-described conjugate to a mammal.
In another embodiment, the present invention comprises a method of detecting the presence of anti-gp120 antibodies in biological test samples .


BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Recombinant proteins and relation to synthetic peptides.
FIG. 2. Reactivity of AIDS patient antibodies to synthetic peptides.
FIG. 3. Reactivity to gp120 of antibodies from HIV+ patient purified over synthetic peptide affinity columns. (A) RIP assay of bound antibodies from the Sp-10 (lane 1), SP-10A (lane 2), SP-11 (lane 3), SP-14 (lane 4), SP-15 (lane 5) and SP-22 (lane 6) affinity columns tested with gp120-III. (B) Reactivity to the surface of H-9 cells infected with HTLV-III in indirect immunofluorescence assays.
FIG. 4. Neutralization of HTLV-IIIB by goat anti-SP-10 antisera.
FIG. 5. Isolate specific neutralization of HIV. Ability of ( ) goat anti-SP-10 antiserum, (o) pre-immune goat serum and ( ) AIDS patient serum to neutralize four different HIV isolates (A) HTLV-III.sub.B (B) HTLV-III.sub.RF (C) HTLV-III.sub.MN (D) HTLV-III.sub.SC.
FIG. 6. Binding of goat anti-SP-10 serum to HTLV-III.sub.B - but not to HTLV-III.sub.RF -infected H9 T cells. (A) Goat antiSP-10 serum (1:200) reacted with 40% of HTLV-III.sub.B -infected H9 T cells compared to HTLV-III.sub.B -infected H9 cells incubated with control (prebleed) goat serum (1:200). (B) Neither goat anti-SP-10 nor control (prebled) serum (1:50) reacted with noninfected H9 T cells. (C) Neither control (prebleed) nor anti-SP-10 serum (1:50) bound to H9 T cells infected with the HTLV-III.sub.RF isolate of HIV.


DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to peptides corresponding to immunogenic epitopes of HIV and synthetic vaccines made therefrom. These novel immunogenic agents are prepared by chemically synthesizing peptides sharing antigenic determinants with the envelope protein of HIV. The peptides are linked to carrier molecules (and/or are polymerized) rendering them suitable as vaccines. These vaccines are useful for immunization against AIDS when administered to mammals, for example, by the parenteral route.
It was determined that peptides that should be studied for immunogenic potential included those corresponding to hydrophilic, charged regions of the HIV envelope glycoprotein. It was further deter mined that, of such peptides, those with predicted beta turns would likely be of particular importance. It was recognized that the formation of intrapeptide disulfide bonds would be useful in establishing native configurational determinants. Also, it was recognized that formation of interchain disulfide bonds would be useful in polymerizing peptide molecules so as to form larger, more immunogenic peptide aggregates.
Computer analysis of the predicted amino acid sequence of the envelope protein of the HTLVIII.sub.B and ARV-2 isolates of HIV established the secondary structure and location cf hydrophilic regions. Secondary structure was determined from the computer analysis using the method of Chou and Fasman (Biochemistry 13:211 and 13:222, 1974; Advances in Enzymology 47:45, 1978). Potential areas of beta turns were localized using the method of Rose (Nature 272:586, 1978). Hydrophilic regions of the envelope protein were identified by the technique of Rose and Roy (Proc. Nat'l. Acad. Sci. USA 77:4643, 1980).
The peptides of the instant invention correspond to, or are homologous with, B-cell epitopes present within the central region of the HIV isolate HTLV-III.sub.B envelope protein, or envelope protein of related HIV isolates. The peptides of the present invention are about 35 amino acids (units) or less in length, are hydrophilic, and when conjugated to appropriate carrier molecules, evoke the production in mammals of high titers (that is, advantageously, a reduction in infectivity of 100 infectious units of approximately 80% in vitro at 1:600 dilution of serum) of type (or isolate) specific neutralizing antibodies against HIV. Unlike the intact gp120 molecule, the peptides themselves are not capab

REFERENCES:
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This invention was made with Government support under Grant No. CA 43447 awarded by the National Institutes of Health. The Government may have certain rights in this invention.
This is a continuation of application Ser. No. 093,854 filed Sept. 8, 1987.

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