Comparative Efficacy of Two, Three, or Four Doses of TY21a Live Oral Typhoid Vaccine in Enteric-Coated Capsules: A Field Trial in an Endemic Area

Ferreccio, Catterine; Levine, Myron M.; Rodríguez, Hector P.; Contreras, Rodrigo A.

doi:10.1093/infdis/159.4.766

Cited by 150 publications

(67 citation statements)

References 8 publications

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“…Taken together, these observations, as well as those recently published [21], add further support to the contention that CVD 909 appears to be as immunogenic after one or two doses as the parent strain (CVD 908htrA) or the licensed Ty21a vaccine, which confers moderate protection in subjects following 3-4 doses of the lyophilized formulation in enteric-coated capsules [2,12,14,15,[36][37][38]. These results support the notion that expression of the capsule did not interfere with the ability of CVD 909 to elicit a wide array of CMI responses, and provide additional impetus for the continuing evaluation of CVD 909 as a leading oral typhoid vaccine candidate.…”

Section: Discussionsupporting

confidence: 58%

Cell-mediated immune responses in humans after immunization with one or two doses of oral live attenuated typhoid vaccine CVD 909

Wahid

Salerno-Gonçalves

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et al. 2007

Vaccine

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CVD 909 is a novel live attenuated S. Typhi oral vaccine candidate derived from strain CVD 908-htrA which constitutively expresses Vi. Herein we investigated whether the genetic manipulations involved in modifying CVD 908-htrA altered its ability to induce potent T-cell immune responses (CMI) after a single dose (5 subjects) and, in a separate trial, whether a second dose (8 subjects) further enhanced its immunogenicity. In these clinical trials we observed that CVD 909 immunization elicits a wide array of CMI, including cytotoxic T cells (CTL), IFN-γ, TNF-α and IL-10 (but not IL-2, IL-4 or IL-5) production, and proliferation to S. Typhi antigens. However, the administration of a second dose did not result in increases in CMI. These results suggest that the genetic manipulations to constitutively express Vi did not adversely affect the ability of CVD 909 to elicit a wide array of CMI responses. These observations add impetus for the continuing evaluation of CVD 909 as a typhoid vaccine candidate.

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Section: Discussionsupporting

confidence: 58%

Cell-mediated immune responses in humans after immunization with one or two doses of oral live attenuated typhoid vaccine CVD 909

Wahid

Salerno-Gonçalves

Tacket

et al. 2007

Vaccine

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“…Strains initially identified in the clinical microbiology laboratory of the Centre pour le Développement des Vaccins, Bamako, Mali (CVD-Mali), as Salmonella serotype Typhi, Paratyphi A, or Paratyphi B or as Salmonella species were shipped to CVD-Baltimore for bacteriological confirmation. The second set was 34 putative Salmonella serovar Paratyphi A and 189 Salmonella serovar Paratyphi B strains isolated from blood cultures of patients in the course of surveillance for enteric fever in Santiago, Chile (4,8,9,(15)(16)(17)(18).…”

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confidence: 99%

PCR Method To Identify Salmonella enterica Serovars Typhi, Paratyphi A, and Paratyphi B among Salmonella Isolates from the Blood of Patients with Clinical Enteric Fever

et al. 2008

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“…In mice inoculated intraperitoneally with serovar Typhi and hog gastric mucin (to estimate the relative degree of attenuation), the 50% lethal dose of CVD 915 (7.7 ؋ 10 7 CFU) was significantly higher than that of wild-type Ty2 (1.4 ؋ 10 2 CFU) and was only slightly lower than that of Ty21a (1. Salmonella enterica serovar Typhi strain Ty21a pioneered the concept that an attenuated strain could be sufficiently well tolerated and protective to gain licensure as a live oral typhoid vaccine (9,27, 32, 46,57). Despite its many positive attributes, Ty21a, which was developed in the early 1970s by chemical mutagenesis of wild-type serovar Typhi strain Ty2 (11), exhibits only modest immunogenicity.…”

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confidence: 99%

Construction, Genotypic and Phenotypic Characterization, and Immunogenicity of Attenuated ΔguaBA Salmonella entericaSerovar Typhi Strain CVD 915

et al. 2001

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A promising live attenuated typhoid vaccine candidate strain for mucosal immunization was developed by introducing a deletion in the guaBA locus of pathogenic Salmonella enterica serovar Typhi strain Ty2. The resultant ⌬guaBA mutant, serovar Typhi CVD 915, has a gene encoding resistance to arsenite replacing the deleted sequence within guaBA, thereby providing a marker to readily identify the vaccine strain. CVD 915 was compared in in vitro and in vivo assays with wild-type strain Ty2, licensed live oral typhoid vaccine strain Ty21a, or attenuated serovar Typhi vaccine strain CVD 908-htrA (harboring mutations in aroC, aroD, and htrA). CVD 915 was less invasive than CVD 908-htrA in tissue culture and was more crippled in its ability to proliferate after invasion. In mice inoculated intraperitoneally with serovar Typhi and hog gastric mucin (to estimate the relative degree of attenuation), the 50% lethal dose of CVD 915 (7.7 ؋ 10 7 CFU) was significantly higher than that of wild-type Ty2 (1.4 ؋ 10 2 CFU) and was only slightly lower than that of Ty21a (1. Salmonella enterica serovar Typhi strain Ty21a pioneered the concept that an attenuated strain could be sufficiently well tolerated and protective to gain licensure as a live oral typhoid vaccine (9,27, 32, 46,57). Despite its many positive attributes, Ty21a, which was developed in the early 1970s by chemical mutagenesis of wild-type serovar Typhi strain Ty2 (11), exhibits only modest immunogenicity. Consequently, three or four spaced doses of Ty21a must be administered to confer an adequate level of enduring protection (9,27, 29, 46,57).9Attenuated ⌬aroC ⌬aroD serovar Typhi strain CVD 908 (18) advanced the field by demonstrating that a live oral typhoid vaccine strain could be clinically well tolerated yet highly immunogenic with a single dose (49, 50). However, 50 and 100% of the subjects who ingested, respectively, 10 7 or 10 8 CFU of CVD 908 manifested silent vaccinemias on one or more occasions between days 4 and 8 after vaccination (50). Although these vaccinemias were not associated with adverse clinical consequences and were spontaneously cleared (50), it was deemed desirable to seek a further derivative that did not cause vaccinemias. This was accomplished by introducing a deletion in htrA, which encodes a stress protein that functions as a serine protease (6). Chatfield et al. (6) had shown that serovar Typhimurium strains harboring mutations in htrA were attenuated and could protect orally immunized mice from a challenge that was lethal for unimmunized control mice. Indeed, in phase 1 and 2 clinical trials, a single dose of CVD 908-htrA proved to be well tolerated and immunogenic but, unlike CVD 908, was not associated with silent vaccinemias (52, 53). Two other attenuated serovar Typhi live oral vaccine candidates, ⌬phoP phoQ strain Ty800 and ⌬cya ⌬crp ⌬cdt strain X4073 have also yielded promising results in phase 1 clinical trials (15, 51). Nevertheless, despite the encouraging results observed in clinical trials with these candidate serovar Typhi va...

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Comparative Efficacy of Two, Three, or Four Doses of TY21a Live Oral Typhoid Vaccine in Enteric-Coated Capsules: A Field Trial in an Endemic Area

Cited by 150 publications

References 8 publications

Cell-mediated immune responses in humans after immunization with one or two doses of oral live attenuated typhoid vaccine CVD 909

Cell-mediated immune responses in humans after immunization with one or two doses of oral live attenuated typhoid vaccine CVD 909

PCR Method To Identify Salmonella enterica Serovars Typhi, Paratyphi A, and Paratyphi B among Salmonella Isolates from the Blood of Patients with Clinical Enteric Fever

Construction, Genotypic and Phenotypic Characterization, and Immunogenicity of Attenuated ΔguaBA Salmonella entericaSerovar Typhi Strain CVD 915

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