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Vaccine Detail

Live attenuated ETEC vaccine ACAM2017
Vaccine Information
  • Vaccine Name: Live attenuated ETEC vaccine ACAM2017
  • Target Pathogen: Escherichia coli
  • Target Disease: Hemorrhagic colitis
  • Tradename: None
  • Vaccine Ontology ID: VO_0000517
  • Type: Live attenuated
  • CS1 gene engineering:
    • Type: Preparation of CFA/II expression
    • Description: ACAM2017 was derived using essentially the same methodology of modifying chromosomal loci via homologous recombination (Daley et al., 2007).
    • Detailed Gene Information: Click Here.
  • Preparation: ACAM2017 was derived from ACAM2007. Genes aroC, ompC, and ompF were deleted, while CS1 and pStrep were added (Daley et al., 2007).
  • Virulence: The vaccine is believed to be safe (Daley et al., 2007).
  • Description: Enterotoxigenic E. coli (ETEC) infection is the single most frequent cause of bacterial diarrhoeal disease worldwide. As immunity to ETEC is strain specific, the ability to create vaccines in vitro which express multiple antigens would be desirable. ETEC expresses a range of colonisation factor antigens (CFAs), which allow adherence ot the mucosal surface and thus colonisation of the intestine. CFA-I, CFA-II, and CFA-IV are the most common antigens encountered in natural ETEC infection. An ideal vaccine againtst ETEC should colonise the intestinal mucosa without causing ijnflammation, and then stimulate a protective immune response. ACAM2017 is a CFA/I expressing vaccine (Daley et al., 2007).
Host Response

Human Response

  • Host Strain: Human
  • Vaccination Protocol: Vaccination Protocol: Vaccination Protocol: Ninety eight healthy adult volunteers (40 men, 58 women) aged 18-49 years were studied. Vaccine doses were prepared in 200ml of Cera Vacx, a buffer solution in order to neutralize gastric acid. The vaccine was tested initially by preforming dose-escalation studies to determiine the highest, safe and tolerated dose. Initially, it was administered using 5*107, 5*108, and 5*109 cfu. The highest dose was used in comparison with placebo. Blood was collected from volunteers 3, 7, 10, 13 days after each dose of vaccine or placebo, and the hightest value used as 'peak' titre or count (Daley et al., 2007).
  • Persistence: Not noted.
  • Side Effects: Nonserious adverse events were recorded in nearly all subjects with equal numbers in vaccine and placebo recipients (Daley et al., 2007).
  • Challenge Protocol: The vaccine was designed to work against enterotoxigenic E. coli (ETEC), but no challenge was performed due to sole interest in immune responses (Daley et al., 2007).
  • Efficacy: Responses to vaccination were assessed using ASC, ALS, serolgy and WGLF. ALS and WGLF responses were consistently clearer than those of ASC and serum IgA (Daley et al., 2007).
  • Description: The vaccine was tested in Phase 1 studies for potential inclusion in a polyvalent oral vaccine. In order to cover the widest range of ETEC subtypes, any poetential vaccine should contain at least CFA-I, CFA-II, and CFA-IV components. This was one of three vaccines involved in the study (Daley et al., 2007).
References
Daley et al., 2007: Daley A, Randall R, Darsley M, Choudhry N, Thomas N, Sanderson IR, Croft N, Kelly P. Genetically modified enterotoxigenic escherichia coli vaccines induce mucosal immune responses without inflammation. Gut. 2007 Jun 12; ; . [PubMed: 17566016].