Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
GENETICALLY ENGINEERED HUMAN IMMUNODEFICIENCY ENVELOPE GLYCOPROTEIN GP120 PRODUCED IN YEAST IS THE TARGET OF NEUTRALIZING ANTIBODIES
Vaccines 87. Modern Approaches to New Vaccines: Prevention of AIDS and Other Viral, Bacterial, and Parasitic Diseases. Chanock RM et al, eds. New York, Cold Spring Harbor Laboratory, p. 236-41, 1987.. Unique Identifier : AIDSLINE ICDB/88647984 Steimer KS; Van Nest G; Dina D; Barr PJ; Luciw PA; Miller ET; Chiron Corp., Emeryville, CA 94608
Abstract:
The development of a vaccine for human immunodeficiency virus (HIV), the etiological agent of acquired immune deficiency syndrome (AIDS), is one of the highest priorities in biomedical research. One approach is to use viral polypeptides produced in genetically engineered microorganisms as subunit vaccine. To obtain such materials, regions of the HIV genome were incorporated into yeast expression vectors. The immunogenicity and antigenicity of these recombinant polypeptides are being evaluated to determine whether they are potential candidates as subunit vaccines for HIV. The viral envelope glycoproteins of HIV are logical candidates as subunit vaccines for AIDS. Results are described evaluating env-2, a recombinant polypeptide from the gp120-coding region of the env gene of HIV-SF2. The objective was to determine whether potentially protective humoral immunity (ie, neutralizing antibodies) recognize this polypeptide. Human sera obtained from HIV-infected individuals have been tested for the presence of neutralizing antibodies that bind to affinity columns of this polypeptide. The ability of env-2 to elicit neutralizing antibodies when injected into experimental animals was also tested. Fractionation of human sera on columns of env-2, a recombinant polypeptide from amino acid 28-491 of the HIV-SF2 env open reading frame (the majority of gp120), bound neutralizing antibodies in sera from nine HIV-seropositive blood donors with high titers of neutralizing activity. A second category of neutralizing antibodies that did not bind to env-2 affinity columns was also found in these sera. When env-2 was injected into mice, antibodies that neutralized the infectivity of HIV-SF2 were elicited. Studies in progress are directed toward identifying the epitopes within env-2 that bind HIV neutralizing antibodies in human sera, identifying the target epitopes of the neutralizing antibodies in human sera that do not bind to env-2, and examining the strain specificity of human HIV-neutralizing antibodies fractionated on env-2 columns. (10 Refs)
Keywords: Acquired Immunodeficiency Syndrome/IMMUNOLOGY Animal Antibodies, Viral/*ANALYSIS AIDS-Related Complex/IMMUNOLOGY Human HIV/IMMUNOLOGY HIV Seropositivity/IMMUNOLOGY Mice *Neutralization Tests Retroviridae Proteins/*IMMUNOLOGY Saccharomyces cerevisiae/GENETICS Vaccines, Synthetic/*IMMUNOLOGY Viral Vaccines/*IMMUNOLOGY MEETING PAPER
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