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N E Byars

Publications and source records attributed to N E Byars.

7 recordsLinked to original sources

Immunological adjuvants: desirable properties and side-effects.

Adjuvants can be used with recombinant antigens to elicit cell-mediated immunity and antibodies of protective isotypes (IgG2a in the mouse and IgG1 in primates). Adjuvants should not produce reactions at injection sites, be pyrogenic or induce anterior uveitis or arthritis. Among 130 analogs of muramyl dipeptides tested, N-acetylmuramyl-L-threonyl-D-isoglutamine showed the greatest separation of potency as an adjuvant from potency in the production of side-effects. A stable emulsion of squalane and the Pluronic polymer L-121 provides a versatile vehicle for targeting of antigens to antigen-presenting cells. The combination of this emulsion with the threonyl analog of MDP is termed Syntex Adjuvant Formulation. This formulation increases the efficacy of influenza, hepatitis B virus, herpes simplex virus, lentivirus and tumor vaccines in experimental animals.

Adjuvants, Immunologic

Improvement of hepatitis B vaccine by the use of a new adjuvant.

Humoral and cellular immune responses of mice and guinea-pigs to hepatitis B virus surface antigen when alum-precipitated or administered with Syntex Adjuvant Formulation (SAF) were compared. Two doses of HBsAg in SAF were sufficient to elicit antibody responses, and using SAF the dose of antigen could be reduced to one-tenth of that required to elicit antibody responses by alum-adjuvanted HBsAg. The use of SAF increased and made more consistent the antibody responses in young mice and in strains of mice with inherited low responses to HBsAg. Cellular responses to HBsAg were more consistently observed when SAF was used than when alum was used. SAF increased the formation of IgG2a antibodies in mice except in the B10.M strain; antibodies of this isotype activate complement and act synergistically with antibody-dependent effector cells more efficiently than antibodies of other isotypes. If SAF proves acceptable for human use it could improve vaccines against hepatitis B virus.

Adjuvants, Immunologic

Adjuvant formulations and their mode of action.

We have developed an adjuvant formulation (SAF) consisting of a synthetic muramyl dipeptide analogue (N-acetylmuramyl-L-threonyl-D-isoglutamine) in a squalane-Pluronic polymer emulsion. Used with a variety of antigens SAF elicits cell-mediated immunity and antibodies of protective isotypes (IgG2a in the mouse). SAF augments responses to influenza virus haemagglutinin and hepatitis B virus surface antigen. Vaccines using SAF have protected guinea pigs against genital herpes simplex virus infections and subhuman primates against Epstein-Barr virus and simian immunodeficiency virus infections. Properties of SAF are compared with those of other adjuvants, including lipopolysaccharide analogs, ISCOMs and liposomes.

Acetylmuramyl-Alanyl-Isoglutamine

Intestinal anaphylaxis in the rat as a model of food allergy.

An animal model of food allergy has been developed in which some aspects of the allergic response could be quantified and the effects of various drugs evaluated. The change in permeability of the intestinal tract of actively sensitized rats, after oral challenge with the sensitizing antigen, was the parameter measured. Rats were sensitized by injection of egg albumin and B. pertussis vaccine to induce reaginic antibody to egg albumin. Two weeks after sensitization, 125I-labelled bovine serum albumin (125I-labelled BSA) was injected intravenously, followed by oral challenge with egg albumin. Pieces of intestinal tissue were obtained and the amount of 125I-labelled BSA determined in a gamma counter. The amount of 125I-labelled BSA in the intestinal tissue of sensitized and challenged rats regularly showed an increase of greater than 100% above values for control rats.

Anaphylaxis