Mouse protective capabilities of Escherichia coli hybrids expressing Salmonella typhi antigens

Abstract

An Escherichia coli hybrid, F1061, expressing Salmonella typhi somatic antigens 9 and 12, and a derivative of this hybrid, E. coli hybrid WR3078, expressing the S. typhi Vi antigen in addition to somatic antigens 9 and 12, were compared with S. typhi Ty2 in experiments to test their ability, as live vaccines, to protect Swiss white mice against death from challenge with a mouse-virulent Salmonella typhimurium hybrid expressing the S. typhi antigens 9, 12, Vi, and d. When the live, vaccinating organisms were administered intraperitoneally, 87.5% of the mice immunized with S. typhi Ty2 survived challenge, as compared with 62.5% of those immunized with E. coli hybrid F1061 and 55% of those inoculated with E. coli hybrid WR3078. When live organisms were administered orally at a dose of 109, 67.5% of the mice immunized with S. typhi Ty2 survived challenge as compared with 47.5% of those immunized with E. coli hybrid F1061 and 40% of those administered E. coli hybrid WR3078. Thus, the protection conferred by E. coli hybrid F1061 expressing only the S. typhi somatic antigens, although significant in this system, was inferior to that conferred by S. typhi Ty2 and the addition of the S. typhi Vi antigen to this hybrid (creating E. coli hybrid WR3078) did not enhance that protection.on August 1, 2020 by guest http://iai.asm.org/ Downloaded from

Evaluation of Two Salmonella typhimurium Hybrids as Challenge Organisms in a System for the Assay of Typhoid Vaccines

“…This importance of the 0 antigen antibodies in the protection of mice against Salmonella infection was suggested earlier by the studies of Ornellas et al (13) and has subsequently been confirmed by the work of Sevenson et al 16as well as that of Lyman et al (12). However, our studies with these S. typhimurium hybrids have also indicated that only those immunogens directed against the 0 antigens of the challenge organism are involved in the vaccine-specific protection conferred in this system; no apparent protective role has been observed for immunogens against either the Vi antigen or the flagellar antigens expressed by the challenge organism (1,(3)(4)(5). Furthermore, one of our earliest studies suggested that expression of the Vi antigen by an S. typhimurium hybrid may alter its virulence characteristics in a manner which adversely affects its ability to respond properly as a challenge organism, with the result that some vaccines protect nonspecifically against such hybrids (1).…”

“…Second, this 0 antigen-specific protective effect is seen more clearly when a Vi-negative hybrid is employed as the challenge organism than when a Vi-positive hybrid is used (1,2). Third, the presence of the Vi antigen in the vaccine or vaccinating strain does not contribute in any observable manner to the protection conferred against a Vi-positive S. typhimurium hybrid challenge organism (1,(3)(4)(5). In addition, the present findings show that the nonspecific protective effect that vaccination with E. coli F464 engenders against a challenge with S. typhimurium hybrid H42 (an effect that we believe is associated with Vi antigen expression by H42) does not occur when the Vi-negative S. typhimurium hybrid Hi is employed in this manner.…”

“…In previous studies with this system (1, 3-5), we have repeatedly observed the inability of vaccination with the Vi antigen to influence protection against S. typhimurium hybrid H42 or any other Vi-expressing S. typhimurium hybrid challenge organisms that we have examined. This has been the case regardless of whether the Vi antigen was administered to the animals intraperitoneally (1,(3)(4)(5) or orally (3,5), in purified form (4,5) or as a component of nonliving vaccinating organisms (1), or, as in the present study, as a component of live vaccinating strains (3). Inasmuch as S. typhimurium hybrid H42 is also seen to be less discriminating as a challenge organism than S. typhimurium hybrid HI, there seems to us no point in further employment of H42 for this purpose.…”

“…Our initial expectation was that the ideal hybrid for this purpose would be one expressing a complete set of these S. typhiderived antigens, i.e., the 0 antigens 9 and 12, the flagellar antigen d, and the Vi antigen. Such a hybrid is S. typhimurium H42, and, indeed, this strain has been employed as a challenge organism in every one of our previous studies with this assay system (1)(2)(3)(4)(5). However, several factors have become apparent during the course of these studies which suggest that an S. typhimurium hybrid expressing only the 0 antigens of S. typhi might be more suitable for this purpose than hybrid H42. In an earlier study (1), we conducted experiments in which S. typhimurium hybrids, ex-pressing different combinations of S. typhi-derived surface antigens, were used as challenge organisms in mice immunized with nonliving vaccines prepared from strains of S. typhimurium, S. typhi, and S. typhimurium hybrids that expressed the S. typhi surface antigens; the results of these experiments indicated that the immune response generated against the 0 surface antigens of the challenge organism is an important factor in determining the ability of the vaccine to protect the animals against death.…”