• Vaccine Name: Live attenuated ETEC vaccine ACAM2010
• Target Pathogen: Escherichia coli
• Target Disease: Hemorrhagic colitis
• Tradename: None
• Vaccine Ontology ID: VO_0000036
• Type: Live attenuated
• Antigen: ETEC colonization factor antigen CFA/I, E. coli heat-stable (ST) toxin, E. coli EAST1 toxin (Daley et al., 2007).
• Sph gene engineering:
  • Type: Preparation for expression of CFA1
  • Description: A new suicide vector (pJCB12) was constructed and used to delete the ST and EAST1 genes and to introduce defined deletion mutations into the aroC, ompC, and ompF chromosomal genes, which generated vaccine candidate strain ACAM2010 (Turner et al., 2006).
  • Detailed Gene Information: Click Here.
• Preparation: ACAM2010 involved the use of parent strain WS-1858B serotype O71:H-. Genes aroC, ompC, and ompF were deleted, while pStrep (plasmid-borne) was 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. ACAM2010 is a CFA/I expressing vaccine (Daley et al., 2007).

Human Response

• Host Strain: Human
• 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*10^7, 5*10^8, and 5*10^9 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. Only DFA-I-specific IgA in serum and WGLF showed clear evidence of a dose-response correlation (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).