Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
DEVELOPMENT OF AN ADJUVANT FORMULATION THAT CAN ELICIT PROTECTIVE IMMUNITY AGAINST RETROVIRUSES
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. 56-9, 1987.. Unique Identifier : AIDSLINE ICDB/88647963 Allison AC; Byars NE; Inst. of Biological Sciences, Syntex Res., Palo Alto, CA 94304
Abstract:
Traditional virus vaccines have included attenuated live viruses, which elicit both humoral and cell-mediated immunity (CMI), and inactivated viruses or their components, which elicit circulating IgG antibodies in sufficient concentration to protect humans from disease. The cloning and expression of the genes for the hepatitis-B virus surface (HBsAg) and core (HBcAg) antigens in yeast and Escherichia coli, and the licensing by the Food and Drug Administration of the former in a vaccine, open up a new chapter in the history of immunization. The full promise of this approach requires the development of an adjuvant formulation that, with virus and other subunit antigens, elicits the production of antibodies of protective isotypes, CMI, and memory in both T- and B-lymphocyte populations. The development of an adjuvant formulation is reported that meets these requirements and appears to be free from unacceptable side effects. A nontoxic small molecule that would be the equivalent of the mycobacterial cell-wall component of Freund's complete adjuvant was identified: the threonyl analog of muramyl dipeptide (MDP). A nonionic detergent with unusual properties--Pluronic L121 triblock polymer--was formulated. Both the MDP analog and Pluronic formulation are required for optimal adjuvant activity: the combination is termed Syntex Adjuvant Formulation-1 or SAF-1. This formulation does not produce tissue damage or elicit an inflammatory reaction at injection sites, and no systemic reaction is demonstrable. A variety of viral subunits, monoclonal immunoglobulins, and other antigens have, when administered im or sc in SAF-1, elicited high titers of antibodies and CMI. Examples of the use of SAF-1 to elicit immunity to viruses include the development of an efficacious vaccine against feline leukemia virus, protection of rhesus monkeys against simian acquired immune deficiency syndrome virus (unsuccessful), and evoking high titers of antibodies using HBsAg in laboratory animals. Collaborative studies have also shown primary and secondary responses to recombinant HBsAg and HBcAg in SAF-1, comparable to those in Freund's complete adjuvant. (6 Refs)
Keywords: Acetylmuramyl-Alanyl-Isoglutamine/ANALOGS & DERIVATIVES/ IMMUNOLOGY Acquired Immunodeficiency Syndrome/IMMUNOLOGY/PREVENTION & CONTROL *Adjuvants, Immunologic Animal Antibody Formation Cats HIV/IMMUNOLOGY Leukemia Virus, Feline/IMMUNOLOGY Macaca mulatta Retroviridae/*IMMUNOLOGY Vaccination Viral Vaccines/ADMINISTRATION & DOSAGE/*IMMUNOLOGY MEETING PAPER
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Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
