New Metabolizable Immunologic Adjuvant for Human Use. 4. Development of Highly Purified Influenza Virus Vaccine in Adjuvant 65

Antibody Response in Man to Hong Kong Influenza Following 1967 Formula Influenza Vaccine in Adjuvant 65

“…Previous reports by our group (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) described the development and clinical evaluation of a new immunologic adjuvant, called adjuvant 65, which has been applied extensively to killed influenza virus vaccine. The adjuvant preparation consists of a water-inpeanut oil emulsion of the aqueous vaccine, employing mannide monooleate ( Arlacel A) as emulsifier and aluminum monostearate as stabilizer.…”

Hyperpotentiation by Synthetic Double-Stranded RNA of Antibody Responses to Influenza Virus Vaccine in Adjuvant 65

“…The previous reports by our group (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) described the development and evaluation of a new immunologic adjuvant named adjuvant 65, which was applied to killed influenza vaccine. The adjuvant preparation consisted of a water-in-peanut oil emulsion of the aqueous vaccine employing mannide monooleate (Arlacel A) as emulsifier and aluminum monostearate as stabilizer.…”

Personal historical chronicle of six decades of basic and applied research in virology, immunology, and vaccinology

“…Virus SV4(, became a prime model for DNA virus oncogenesis and tumor prevention (81), for the discovery of P53 oncogene(82), and for elucidating molecular mechanisms in viral and eukaryotic cell processes (see (83)),Virai influenza vaccineThe toxigenicity of early influenza virus vaccities was remarkably diminished in our laboratories (unpubhshed) by combined microfiltration and density gradient procednres to remove bacteria and otber impurities. Purified virus vaccines(84) were hcensed in 1969 and 1970, The immunizing potency of the killed vaccine was vastly enhanced by formulation in our new water-in-oil preparation of metabolizable peanut oil (adjuvant 65) (84-87), A license for the vaccine was granted in ! 973 hy the licensing authority in the United Kingdom, Subsequent requirement by the U S. regulatory control authority that we develop and use purified mannide monooleate and aluminum monostearate in the adjtivant formulation resulted in loss of adjuvant activity and enhancing potency (ttnpubhshed) and the product was abandoned, Piasma-derived hepatitis B vaccine (see Table 2) Bluniberg's discovery ofthe surface antigen of hepatitis B virus in the blood of human carriers, together with the observation that antibody against this antigen devekjps following natural hepatitis B infection, provided a hasis (see Tahle I) for helief that a vaccine prepared using the viral surface antigen might protect against the infection in nature, Basic research studies that would lead to a plasma-derived hepatitis B vaccine was initiated by us in 1968, The produ ct was licensed in 1981, after 13 years of pioneering and complex laboratory studies to develop a safe and effective vaccine (88-92), The hepatitis B virus does not grow in cell culture and the problem of assuring freedom from live hepatitis B virus and from other undetectable agents that might be present in human blood was formidable, A process was developed for purification and inactivation of surface antigen that involved three steps, viz, pepsin digestion, 8-molar urea denaturation-renaturation, and treatment with formaldehyde.…”