The Use of Adjuvants in Studies on Influenza Immunization

Abstract

Rather early in studies on influenza immunization in animals as well as in man, it was realized that immunizing effect, as reflected in antibody response induced by the vaccines employed, was limited and of relatively short duration. For these reasons (1) a variety of methods were explored for enhancing and prolonging the protective effect induced by vaccination (2-7). None, however, provided such striking results as those obtained in studies in animals reported by Friedewald (6), and in studies in man reported by Henle and Henle (7). These investigators used vaccines consisting of virus in water-in-oil emulsions in the manner developed in recent years by Freund (8).Although the immunologic data derived by Friedewald and the Henles were outstanding, in comparison to the effects induced by vaccines consisting of virus in an aqueous medium alone, the immunologic success was blighted by the occurrence of undesirable reactions at the site of inoculation. The problem remaining after these experiences seemed merely to be one of reducing or eliminating the untoward local reaction while retaining the immunologic advantage. That this could be accomplished was evident from observations made, in the course of certain other studies (9), when it was found that rather large doses of water-in-oil emulsions without acid-fast bacilli could be inoculated into monkeys without untoward local reactions. In the studies referred to reagents were used which were different from those employed by Friedewald and the Henles and the inoculum was introduced intramuscularly rather than subcutaneously.When influenza virus vaccine was prepared in this particular water-in-oil emulsion and administered to monkeys intramuscularly, it too could be given without producing undesirable effects at the inoculation site.

Studies on the chemical basis of the antigenicity of proteins. 1. Antigenicity of polypeptidyl gelatins

“…Immunization procedure. The antigens used were incorporated in a water in oil-adjuvant mixture, according to Salk & Laurent (1952). Ten parts of 5% gelatin-derivative solution, 1 part of Arlacel A (Atlas Powder Co., Wilmington, Del., U.S.A.) and 9 parts of Bayol F (Stanco Distributors, New York, U.S.A.) were homogenized by repeated filling and forcible ejection from a syringe.…”

Old and new adjuvants

“…Muramyl dipeptide expressed by MTb in CFA activates NOD2 receptors [67,68]. Incomplete Freund’s adjuvant (IFA) composed of just the mineral oil component of CFA, was used in influenza vaccines in the 1950s to enhance antibody responses [69], and due to significant side effects [70] has only been studied in clinical trials of HIV and some cancer vaccines [71]. It enhances accumulation of APCs, antigen uptake and cytokine production and a non-polarized TH1/TH2 response with enhanced IgG1/IgG2a antibody responses [72–76].…”

The use of nonhuman primates in research on seasonal, pandemic and avian influenza, 1893–2014

“…However, the failure of the same vaccine to have any impact on the 1947 epidemic led both to the recognition of antigenic variation, implying that new vaccines would be needed each flu season, and to efforts to increase vaccine potency. In the first study of influenza vaccines employing NHPs, Jonas Salk and his colleagues reported in 1951 and 1952 that the standard vaccine prepared in a water-in-oil emulsion and delivered intramuscularly to rhesus macaques elicited a much stronger antibody response than the vaccine without adjuvant (Salk and Laurent, 1952;Salk et al, 1951) (Table S6). The animals were not subsequently challenged with influenza virus.…”