Adjuvant Activity of a Novel Metabolizable Lipid Emulsion with Inactivated Viral Vaccines

Infect Immun. 1980 June; 28(3): 937–943.

PMCID: PMC551041

J. A. Reynolds,^† D. G. Harrington,¹ C. L. Crabbs,¹ C. J. Peters,¹ and N. R. Di Luzio²

¹United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21701

²Tulane University School of Medicine, Department of Physiology, New Orleans, Louisiana 20112

^†Present address: Pfizer Central Research, Groton, CT 06340.

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Abstract

Studies were conducted in mice, hamsters, sheep, and two species of nonhuman primates which demonstrate the adjuvant activity of a new metabolizable lipid emulsion with marginally immunogenic doses of Formalin-inactivated viral vaccines. The lipid base consists of highly refined peanut oil emulsified in aqueous vaccines with glycerol and lecithin. Hamsters and mice inoculated with lipid emulsion plus western or Venezuelan equine encephalitis vaccine were significantly more resistant than vaccinated controls to lethal homologous virus challenge. Sheep given one dose of lipid emulsion plus Rift Valley fever vaccine developed significantly higher antibody titers than control sheep receiving only vaccine. Cynomolgous monkeys inoculated with lipid emulsion plus Rift Valley fever vaccine developed 16-fold greater peak primary and 20-fold greater secondary antibody titers than those of vaccine controls. Similar lipid emulsion-Rift Valley fever studies in rhesus monkeys resulted in 37- and 300-fold increases in primary and secondary titers, respectively, compared with monkeys given vaccine alone. Neither the sequence of combining antigen with lipid nor the exact ratio of aqueous phase to lipid phase affected the survival of Venezuelan equine encephalitis-vaccinated mice challenged with homologous lethal virus. This lipid formulation has several advantages over other water-in-oil adjuvants for potential use in humans. The components are metabolizable or normal host constituents, it is easily emulsified with aqueous vaccines by gentle agitation, and it is relatively nonreactogenic in recipients.

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