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Vaccine Comparison

inactivated ETEC expressing expressing CFA/I and CFA/II Live attenuated ETEC vaccine ACAM2007 Live attenuated ETEC vaccine ACAM2010 Live attenuated ETEC vaccine ACAM2017
Vaccine Information Vaccine Information Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0000502
  • Type: Inactivated or "killed" vaccine
  • Antigen: The antigen used in this vaccine was ETEC bacteria expressing fimbrial colonization factor antigens I and II (CFA/I and CFA/II) (Wennerås et al., 1992).
  • Adjuvant: cholera toxin B subunit
    • VO ID: VO_0001242
    • Description: cholera toxin B subunit (CTB). However, it was found that CTB did not function as a mucosal adjuvant, since CFA-specific ASC responses were not enhanced by the simultaneous administration of CTB (Wennerås et al., 1992).
  • Preparation: Each vaccine consisted of 1011 formalin-killed ETEC bacteria expressing CFA/I and CFA/II (CS1, CS2, and CS3). The following strains were used: an ST-positive 078:H12 strain expressing CFA/I, a toxin-negative 0139:H28 strain expressing CS1, and an ST-positive 06:H16 strain expressing CS2 and CS3 The strains were grown under conditions leading to a high level of expression of the different CFAs, and thereafter the organisms were killed by mild formalin treatment, preserving 50 to 100% of the CFA activity. The inactivated bacteria were mixed to give a total of 1011 formalin-killed E. coli bacteria in 4 ml of phosphate-buffered saline, corresponding to one vaccine dose. The CFA/I proteins used in the vaccine were purified from a flagellum-deficient mutant of strain H10407 by homogenization with a blender followed by ammonium sulfate fractionation and negative diethylaminoethyl-Sephadex column chromatography. Purified CFA/II (CS1 plus CS3) protein was prepared from strain E1392-75 by homogenization followed by salt precipitation and column chromatography (Wennerås et al., 1992).
  • Tradename: None
  • Vaccine Ontology ID: VO_0000511
  • Type: Live attenuated
  • Antigen: ETEC CFA/II: CS2 and CS3 (Daley et al., 2007).
  • Sph gene engineering:
    • Type: Preparation of expression of CFA/II
    • Description: Colonisation factor antigens allow adherence ot the mucosal surface and thus colonisation of the intestine (Daley et al., 2007).
    • Detailed Gene Information: Click Here.
  • Preparation: ACAM2007 was derived from WS-3504D Serotype O39: H12. Genes aroC, ompC, and ompF were deleted, while pStrep 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. ACAM2007 is a CFA/II expressing vaccine (Daley et al., 2007).
  • 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).
  • 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 Host Response Host Response Host Response

Human Response

  • Vaccination Protocol: Thirty-seven healthy adult individuals participated in this study. Thirty-one volunteers received three oral doses of a prototype ETEC vaccine, with a 2-week interval between doses; six volunteers were studied for control purposes only. To provide the CTB component, 21 of the vaccinees also received a dose of oral cholera vaccine, consisting of 1 mg of purified CTB and 1011 killed Vibrio cholerae O1 organisms together with the ETEC expressing the various CFAs (CFA+ ETEC) (Wennerås et al., 1992).
  • Immune Response: ASC responses to both CFAs were comparable in magnitude and isotype distribution, with IgA-ASCs dominating the response. After three oral immunizations, the vaccinees had, respectively, 14- and 11-times-higher geometric mean levels of IgA-ASCs directed against CFA/I and CFA/II than did nonimmunized controls. The geometric means of specific IgA-ASCs postvaccination were 31 per 107 MNC for CFA/I and 23 per 107 MNC for CFA/II. Although less pronounced, IgM-ASC responses to the CFAs were also detected in most vaccinees. After three immunizations, the geometric means of IgM-ASCs were 11 and 6 times higher for CFA/I and CFA/II, respectively, than in nonimmunized controls. CFA-specific IgG-ASCs were rarely detected. Specific ASC responses to the CTB component of the vaccine were detected in all volunteers but differed from CFA-specific responses with respect to isotype distribution. The results of this study suggest that two oral immunizations are efficient at inducing optimal CFA-specific responses, since the numbers of CFA-ASCs were not increased but rather were decreased upon administration of a third dose of vaccine. (Wennerås et al., 1992).
  • Side Effects: A few of the vaccinees experienced slight abdominal discomfort for a couple of hours on the day of either the first or second immunization (Wennerås et al., 1992).
  • Efficacy: Almost 90% of the volunteers developed CFA-specific ASC responses after vaccination (Wennerås et al., 1992).

Human Response

  • Host Strain: Human
  • 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).

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*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. 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).

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 References References References
Wennerås et al., 1992: Wennerås C, Svennerholm AM, Ahrén C, Czerkinsky C. Antibody-secreting cells in human peripheral blood after oral immunization with an inactivated enterotoxigenic Escherichia coli vaccine. Infection and immunity. 1992; 60(7); 2605-2611. [PubMed: 1612730].
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].
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].
Turner et al., 2006: Turner AK, Beavis JC, Stephens JC, Greenwood J, Gewert C, Thomas N, Deary A, Casula G, Daley A, Kelly P, Randall R, Darsley MJ. Construction and phase I clinical evaluation of the safety and immunogenicity of a candidate enterotoxigenic Escherichia coli vaccine strain expressing colonization factor antigen CFA/I. Infection and immunity. 2006 Feb; 74(2); 1062-71. [PubMed: 16428753].
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].