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Vaccine Detail
E. coli O157:H7 intimin vaccine |
Vaccine Information |
- Vaccine Name: E. coli O157:H7 intimin vaccine
- Target Pathogen: Escherichia coli
- Target Disease: Hemorrhagic colitis
- Vaccine Ontology ID: VO_0000110
- Type: Subunit vaccine
- Antigen: The antigen used in this vaccine was Int280α, which is the recombinant LEE-encoded protein from EPEC strain E2348/69. Int280α, a specific type of intimin, is the target of long-lived humoral immune responses in C. rodentium-infected mice. (Ghaem-Maghami et al., 2001).
- Adjuvant:
- Preparation: A highly purified preparation of recombinant Int280α from EPEC E2348/69 was used as an immunogen in mucosal and parenteral vaccination regimes (Ghaem-Maghami et al., 2001).
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Host Response |
Mouse Response
- Host Strain: C3H/Hej
- Vaccination Protocol: Mice were immunized i.n. three times, on days 0, 14, and 28, with 10 μg of Int280α with or without an enterotoxin-based adjuvant for the mucosal regimes (Ghaem-Maghami et al., 2001).
- Immune Response: Mice vaccinated intranasally were administered 10 μg of Int280α mounted serum IgG1 and IgG2a, but not IgA, antibody responses to Int280α. Codelivery of 1 mg of LT, LTR72, or LTK63 with Int280α significantly increased the serum IgG1 and IgG2a antibody response to Int280α. Moreover, the addition of a mucosal adjuvant resulted in the induction of Int280α-specific serum IgA responses. Analysis of Int280α-specific IgG subclasses in i.n. immunized mice showed a predominance of IgG1 over IgG2a. As occurred in s.c. immunized mice, the ratio of IgG1 to IgG2a was reduced when Int280α was coadministered with an enterotoxin-based adjuvant (Ghaem-Maghami et al., 2001).
- Challenge Protocol: In separate experiments, mice were orally challenged with between 2 × 10^7 to 3 × 10^7 CFU of DBS255(pCVD438) 13 or 16 days after the last immunization. Mice were killed 14 days postchallenge, the colon of each mouse was weighed and homogenized, and the pathogen burden was determined by viable count (Ghaem-Maghami et al., 2001).
- Efficacy: Mice immunized i.n. with PBS or an adjuvant had uniformly high C. rodentium counts in the colon. The pathogen burden was reduced, however, if mice were immunized i.n. with Int280α alone. As occurred in s.c. immunized animals, the addition of a mucosal adjuvant with Int280α negated some of the protective efficacy of i.n. vaccination using Int280α alone (Ghaem-Maghami et al., 2001).
Mouse Response
- Host Strain: C3H/Hej
- Vaccination Protocol: Mice were subcutaneously immunized three times, on days 0, 14, and 28, with 10 μg of Int280α with or without adjuvant.
- Immune Response: Mice immunized with Int280α in the absence of adjuvant mounted serum IgG1 and IgG2a but not IgA antibody responses to Int280α. The coadministration of LT or LTR72 with Int280α prompted a more rapid Ig response to Int280α but did not, however, increase the magnitude of the final Int280α-specific IgG1 or IgG2a titer compared to that obtained in mice s.c. immunized with Int280α alone. Surprisingly, s.c. coadministration of LT or LTR72 with Int280α prompted a weak Int280α-specific serum IgA response, although this occurred in only a small number of mice. Int280α-specific IgG1 was the predominant IgG subclass elicited by parenteral vaccination, although the ratio of IgG1 to IgG2a was reduced when Int280α was coadministered with the adjuvant LT or LTR72 (Ghaem-Maghami et al., 2001).
- Challenge Protocol: In separate experiments, mice were orally challenged with between 2 × 10^7 to 3 × 10^7 CFU of DBS255(pCVD438) 13 or 16 days after the last immunization. Mice were killed 14 days postchallenge, the colon of each mouse was weighed and homogenized, and the pathogen burden was determined by viable count (Ghaem-Maghami et al., 2001).
- Efficacy: The colons of mice immunized s.c. with Int280α alone harbored significantly fewer challenge bacteria than the colons of naive or control animals (Ghaem-Maghami et al., 2001).
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References |
Ghaem-Maghami et al., 2001: Ghaem-Maghami M, Simmons CP, Daniell S, Pizza M, Lewis D, Frankel G, Dougan G. Intimin-specific immune responses prevent bacterial colonization by the attaching-effacing pathogen Citrobacter rodentium. Infection and immunity. 2001; 69(9); 5597-5605. [PubMed: 11500434 ].
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