Immunization with radiation-attenuated malaria sporozoites induces potent cellular immune responses, but the target antigens are unknown and have not previously been elicited by subunit vaccines prepared from the circumsporozoite (CS) protein. A method is described here for inducing protective cell-mediated immunity to sporozoites by immunization with attenuated Salmonella typhimurium transformed with the Plasmodium berghei CS gene. These transformants constitutively express CS antigens and, when used to immunize mice orally, colonize the liver, induce antigen-specific cell-mediated immunity, and protect mice against sporozoite challenge in the absence of antisporozoite antibodies. These data indicate that the CS protein contains T cell epitopes capable of inducing protective cell-mediated immunity, and emphasize the importance of proper antigen presentation in generating this response. Analogous, orally administered vaccines against human malaria might be feasible.
Shigella sonnei, an intestinal pathogen, produces a characteristic form I cell surface antigen now known to be plasmid encoded. We considered that the GalE Salmonella typhi Ty21a oral vaccine strain, highly effective against typhoid, might be modified so as to be protective also against shigellosis due to S. sonnei. The plasmid responsible for form I antigen synthesis was therefore conjugally transferred to the galE S. typhi strain. Serological studies revealed that the derivative strain produces the form I antigen in addition to the normal S. typhi somatic antigens. Testing in mice demonstrated that the derivative form I galE S. typhi strain is protective against both S. sonnei and S. typhi challenges. These data suggest that the galE S. Ty21a oral vaccine strain, which presumably stimulates the local immune system in the intestine, may also serve as a useful carrier for other antigenic determinants to protect against different intestinal infections.
Two of seven sucrose-fermenting Salmonella strains obtained from clinical sources were found capable of conjugal transfer of the sucrose fermentation (Scr+) property to the Escherichia coli K-12 strain WR3026. The genetic elements conferring this Scr+ property, designated scr-53 and scr-94, were then conjugally transmissible from E. coli WR3026 Scr+ exconjugants to other strains of E. coli at frequencies of 5 x 10-I to 5 x 10-I for the scr-53 element and 10 6 to 10-s for the scr-94 element. In E. coli hosts, both of these elements were compatible with F-lac and with each of six previously characterized transmissible lac elements. No antibiotic resistance characteristics or colicin production were discovered to be associated with either scr-53 or scr-94. Neither scr element generated a male host response to the female-specific phage XII, but the scr-53 element rendered its E. coli host sensitive to the male-specific phage R-17. E. coli hosts containing scr-53 were susceptible to lysis by Plvir, and transduction of the scr-53 element was accomplished with this phage. The scr-53 element was isolated from E. coli WR3026, Scr+ transductants, and E. coli WR2036 Scr+ exconjugants as a covalently closed circular deoxyribonucleic acid molecule with a molecular weight (determined by electron microscopy) of approximately 52 x 106. Receipt of the scr-94 element rendered E. coli hosts of this element unsusceptible to lysis by Plvir, although adsorption of the phage by an E. coli WR3026 exconjugant containing scr-94 occurred as efficiently as it did on WR3026 itself. Repeated examination of E. coli strains harboring scr-94, as well as of the Salmonella strain which initially contained it, did not reveal the presence of circular deoxyribonucleic acid. The synthesis of the sucrose cleaving enzyme was inducible in E. coli exconjugants containing either scr-53 or scr-94.
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