Subjects: Healthy, HIV-1 uninfected adult volunteers with lower-risk behavior for HIV-1 infection.
Schema: Double-blind, randomized placebo-controlled evaluation, 7 treatment arms, 15 subjects per arm; 5 subjects in placebo arm. [Number of Subjects = 110]
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Adjuvants: |
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Schedule (Months) |
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15 |
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15 |
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15 |
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15 |
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15 |
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15 |
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15 |
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5 |
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ACCRUAL, IMMUNIZATIONS AND FOLLOW-UP COMPLETED
Product Description: CHO cell-derived HIV-1 SF-2 rgp120 [Chiron/BIOCINE]; adjuvants described on following page.
Time Period: First volunteer entered on 06/07/93 and the last on 10/26/93; original follow-up of 18 months extended to 27 months for those volunteers receiving fourth immunization, and an additional follow-up of 2 months after special DTH study
Clinical Sites: Saint Louis University, University of Rochester, University of Washington, Vanderbilt University
Study Chair: Julie McElrath, University of Washington
INCLUSION CRITERIA
Standard inclusion criteria.
EXCLUSION CRITERIA
Standard exclusion criteria.
STUDY GOALS
To determine the relative safety and immunogenicity of rgp120 when administered individually in combination with of a panel of adjuvants.
ADJUVANT DESCRIPTIONS
Manufacturer - Superfos a/s: Alum, denoting aluminum salts which may include aluminum phosphate or aluminum hydroxide, has been used as an adjuvant since the 1920s, and is the only adjuvant approved by the FDA for use in licensed human vaccines. Bacterial toxoid vaccines are formulated with alum and have been in use for decades in infants, children and adults. The adjuvant has proven safety when administered intramuscularly and has been formulated with candidate HIV-1 vaccines in previous AVEG trials. Alum used in these studies will be aluminum hydroxide (Alhydrogel).
Manufacturer - RIBI: Monophosphoryl Lipid A (MPL). Bacterial lipopolysaccharide endotoxin (LPS), and specifically its active moiety, lipid A, has been shown to be a potent immunologic adjuvant. Native dephosphorylated lipid A (DPL) is reactogenic and pyrogenic; however, simple chemical modifications to DPL result in nontoxic preparations which retain the adjuvant activity of DPL. The adjuvant to be employed in these studies is lipid A purified from Salmonella minnesota R595. Purified native lipid A is detoxified by removal of the phosphate group from the reducing end of the disaccharide back-bone of DPL by acid hydrolysis, producing MPL. Mono-phosphoryl lipid A is further detoxified by 3-O-deacylation with mild alkaline hydrolysis. Liposomes composed of phospholipids and cholesterol and also containing MPL will be formulated under GMP conditions. Monophosphoryl lipid A at 50 µg per dose will be formulated with antigen in a 0.25% squalene emulsion.
Manufacturer - WRAIR: Alum-adsorbed liposomes containing monophosphoryl lipid A. This adjuvant preparation consists of liposomes made of phospholipids and cholesterol and contains monophosphoryl lipid A (MPL). A histologic assessment of the reactivity of alum-adsorbed liposomes containing lipid A administered either IM or IV was performed in mice. At 72 hours, an inflammatory response was noted with a predominance of macrophages containing phagocytized lipid material. Liposomes have been administered to over 200 individuals primarily for diagnostic, biodistribution, and therapeutic studies since the mid-1970s with no major difficulties.
Manufacturer - Chiron/BIOCINE: SAF-m Adjuvant with and without MDP. The Syntex adjuvant formulation (SAF-m) is an emulsion consisting of squalene, Pluronic L121 block polymer and Tween 80 in phosphate-buffered saline. Various preparations of the SAF-m adjuvant with and without threonyl muramyl dipeptide (Termutide; N-acetylmuramyl-L-threonyl-D-Isoglutamine; MDP) have been tested in humans, guinea pigs, mice, rabbits, goats, baboons, and monkeys. In these studies, the SAF-m adjuvant, in combination with influenza, HSV gD2, and HIV-1 immunogens, has shown superior immunogenicity to that of alum and in some cases to that of MF59.
Manufacturer - Ciba/Geigy: MF59 ± MTP-PE. The adjuvant emulsion, MTP-PE/MF59, contains a muramyl tripeptide (MTP) linked covalently with dipalmitoyl phosphatidylethanolamine (PE) and MF59, a microfluidized emulsifier system consisting of polysorbate 80 and sorbitan trioleate. The concentration of MTP-PE used in this study was 50 µg. In one study arm, the preparation used contained MF59 without MTP-PE.