Chemically-Modified Crude Endotoxins as Possible Typhoid Vaccines

Abstract

As part of an effort to develop a typhoid vaccine which retained its immunogenicity, but exhibited reduced host toxicity, two methods of chemically modifying the endotoxin moiety were studied. Crude preparations of endotoxin were treated either with acetic anhydride or potassium methylate. The products, along with the parent crude endotoxin, were then characterized by mouse toxicity studies, pyrogen tests in rabbits, and active protection tests in mice. Neither chemically-modified preparation was lethal for mice in doses used for immunization. The minimal pyrogenic dose (MPD) for the acetylated derivative was 100 ug, while that for the methylated preparation was essentially unchanged from the MPD of the parent material (approximately 0.1 ug). Compared with the commercially available heat-killed, phenol-preserved (HP) typhoid vaccine, doses of the acetylated and methylated products which protected mice as well as the HP vaccine were 300 times and 15 times less pyrogenic, respectively. These studies suggest possible alternatives to the toxic HP typhoid vaccine currently in use.