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Vaccine Comparison

Avirulent Salmonella vaccine strain carrying C. jejuni cjaA gene Inactivated C. jejuni whole-cell (CWC)
Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0004121
  • Type: Recombinant vector vaccine
  • Antigen: Three C jejuni genes [cjaA ( cj0982c ) , cjaC ( cj0734c ) and cjaD ( cj0113 )] encoding highly immunogenic proteins which are conserved among different Campylobacter serotypes have been introduced into avirulent Salmonella enterica sv. Typhimurium (chi 4550 and chi 3987) strains of two different serotypes (UK-1 and SR) (Wyszynska et al., 2004). C. jejuni 72Dz/92 cjaA gene encodes a highly immunogenic protein which is conserved among different Campylobacter serotypes (Wyszynska et al., 2004). The surface antigen CjaA of Campylobacter jejuni is supported by the presence of an upstream gene with significant homology to ATP binding proteins (Martin et al., 1999).
  • cjaA gene engineering:
    • Type: Recombinant vector construction
    • Description: pUWA10A plasmid carrying CjaA was ligated into the pYA3341 plasmid and then transformed into E. coli χ6097 competent cells. It was later introduced by electroporation into two S. enterica sv. Typhimurium (χ3987 and χ4550) strains (Wyszynska et al., 2004).
    • Detailed Gene Information: Click Here.
  • Adjuvant: E. coli heat-labile toxin, LT
  • Preparation: Three gene libraries of Campylobacter jejuni 72Dz/92 DNA were prepared using lambda gt11, pSupercos and pWSK129 cloning vectors. Screening of the libraries revealed several immunoreactive clones (Pawelec et al., 1997).
  • Virulence: The vaccine vector is avirulent Salmonella enterica sv. Typhimurium (chi 4550 and chi 3987) strains of two different serotypes (UK-1 and SR) (Wyszynska et al., 2004).
  • Description: The constitutive expression of all analysed genes as measured by Western immunoblot technique was independent of the particular host strain. Specific rabbit anti-rCjaA antibody reacted not only with CjaA but also with other solute-binding proteins, components of the ABC transport system (CjaC protein), chosen as the protective antigen for animal experiments. Chickens orally immunized with Salmonella expressing Campylobacter cjaA gene developed serum IgG and mucosal IgA antibody responses against Campylobacter membrane proteins and Salmonella OMPs. Protection experiments show that chicken immunization with avirulent Salmonella carrying Campylobacter cjaA gene greatly reduces ability of heterologous wild type C. jejuni strain to colonize the bird cecum (Wyszynska et al., 2004).
  • Vaccine Ontology ID: VO_0004100
  • Type: Inactivated or "killed" vaccine
  • Antigen: inactivated whole-cell Campylobacter jejuni (CWC)
  • Adjuvant: E. coli heat-labile toxin, LT
    • VO ID: VO_0001322
    • Description: 25 mg of a mucosal adjuvant, the heat-labile enterotoxin of Escherichia coli (LT) has been used (Baqar et al., 1995b).
  • Preparation: The CWC vaccine is prepared from the 81-176 strain of C. jejuni and consists of a 1:1 mixture of heat (60 C, 60 min)- and formalin (0.02 M)-inactivated Campylobacter whole cells. Each vaccination group receives oral doses of CWC vaccine containing bacterial cells alone or in combination with 25 mg of LT. Just prior to vaccination, gastric acidity is neutralized by 2 doses of a 5% NaHCO3 solution (pH 8.5) with a 15-min interval (Baqar et al., 1995b).
  • Virulence: Volunteers given the CWC vaccine have similar IgA-ASC and sIgA responses and in vitro induction of IFN to Campylobacter antigens (Walker, 2005).
  • Description: Whole-cell vaccine formulations deserve further evaluation as candidate vaccines and the potential value of mucosal adjuvants, like LT, in enteric vaccine development are not in doubt (Baqar et al., 1995).
Host Response Host Response

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were orally immunized in a three-dose primary series with CWC vaccine particles alone or in combination with a mucosal adjuvant, the heat-labile enterotoxin of Escherichia coli (LT) (Baqar et al., 1995b).
  • Persistence: Ninety percent of control animals remain colonized for 9 days post-challenge. A similar colonization pattern is observed in mice vaccinated with LT alone. Clearance of challenge organisms from mice receiving CWC vaccine alone appear to be dependent on the amount of vaccine administered. Although 80% of the mice receiving the highest vaccine dose cleared the infection within 3 days of challenge, the remaining 20% were colonized for the remainder of the study period (Baqar et al., 1995b).
  • Immune Response: Campylobacter-specific intestinal IgA responses are dependent on the use of LT, whereas IgA and IgG responses in serum are not. Intestinal lavage fluid collected from sham-immunized animals at 7 d post-vaccination have no detectable levels of Campylobacter- or LT-specific secretory IgA (sIgA) or IgG. When CWC is administered over a 10,000-fold range of doses, only 20% of the mice immunized with the low or intermediate doses mount a significant Campylobacter-specific sIgA response. In contrast, administering the same doses with LT resulted in a substantial enhancement of the sIgA response to vaccine-associated Campylobacter antigens in all vaccination groups (Baqar et al., 1995b).
  • Side Effects: Both the CWC and CWC-LT vaccine formulations are well tolerated, with no weight loss or signs consistent with toxicity in immunized animals. Histopathological examination of the intestinal mucosa and other organ systems following vaccination fails to detect evidence of tissue damage or severe inflammation (Baqar et al., 1995b).
  • Challenge Protocol: At ~4 wks post-vaccination, mice were challenged orally with C. jejuni, and duration of colonization was determined by the monitoring of fecal shedding. Efficacy was determined by measuring the degree of protection afforded against intestinal colonization and systemic dissemination of challenge organisms (Baqar et al., 1995b).
  • Efficacy: Colonization resistance was induced over a broad range of vaccine doses when LT was included. However, only the highest dose of CWC alone gave comparable levels of protection. Both formulations provided equivalent protection against systemic spread of challenge organisms. These results indicate that both whole-cell vaccine formulations deserve further evaluation as candidate vaccines and also highlight the potential value of mucosal adjuvants, like LT, in enteric vaccine development (Baqar et al., 1995b).
  • Description: Inactivated Campylobacter whole-cell vaccines (CWC) must be given orally in large doses to be effective. Drawbacks could be overcome by the coadministration of LT (Baqar et al., 1995b).

Chicken Response

  • Host Strain: Commercial broiler chickens (Gallus gallus)
  • Vaccination Protocol: Commercial broiler chickens were obtained from the local hatchery on the day of hatch. Briefly, chickens deprived of food and water for 4 h were immunized orally with 100 μl of 109 CFU/ml of Salmonella χ3987 carrying pUWM251 (cjaA). Booster doses were administrated 2 weeks after primary immunization. Following vaccination, chickens were observed for the development of diarrhoea and other potential adverse side effects (Wyszynska et al., 2004).
  • Persistence: There was high anti-Campylobacter IgG titer present at the first time point (week 0), dropping at weeks 2 and 4. A moderate increase of Campylobacter specific IgG level was observed at week 6 followed by significant increase of anti-Campylobacter IgG level at week 8. Serum IgG titers to Campylobacter whole cell lysates followed a similar pattern, as those measured with membrane antigens, with respect to time, although the increase of anti-Campylobacter IgG titer at week 8 was not so significant. The results suggest that high IgG titer observed at the 0 week reflects maternally derived immunity while increasing serum IgG titers at 6 and 8 weeks is a consequence of vaccination (Wyszynska et al., 2004).
  • Immune Response: Mucosal anti-Salmonella and anti-Campylobacter IgA antibodies were present in samples taken from chickens inoculated with Salmonella/pUWM251 at every tested time point. In contrast to serum IgG, the kinetics of IgA responses to both antigens were similar. In intestinal secretions the level of the antibodies dropped at week 2 and then peaked 2 weeks after the booster. During the next 2 weeks, IgA titers decreased and maintained at almost the same level during the remainder of the experiment. Since IgA antibodies directed towards both antigens were present in the intestinal fluids of 1-day-old birds, similarly to IgG antibodies, IgA present at 0 week were maternally derived. In intestinal secretions, taken from different parts of chicken gut (rectum and jejunum), levels of IgA antibodies to Campylobacter and Salmonella antigens also peaked 2 weeks after the secondary immunization. Intestinal IgA titers to Campylobacter whole cell lysates followed the similar patterns as those measured with membrane antigens (Wyszynska et al., 2004).
  • Side Effects: No adverse side effects were observed (Wyszynska et al., 2004).
  • Challenge Protocol: Two weeks after booster, all chicks received a dose containing approximately 2×109 CFU/ml of the wild type C. jejuni/pUOA18 strain in 0.1 ml PBS with gelatine. Campylobacter colonization was confirmed on days 3, 6, 9 and 12 after the challenge. In each instance, four chicks were euthanized, the intestine was excised and the C. jejuni present in chicken cecal contents were enumerated by plating (Wyszynska et al., 2004).
  • Efficacy: Protection experiment showed that chicken immunization with avirulent Salmonella carrying Campylobacter cjaA gene greatly reduced the ability of heterologous wild type C jejuni strain to colonize the bird cecum (Wyszynska et al., 2004).
  • Description: It is well documented that poultry and poultry products are the major source of human campylobacteriosis and salmonellosis. The avirulent Salmonella vaccine strains expressing Campylobacter antigen can be potentially used as a bivalent chicken vaccine (Wyszynska et al., 2004).

Chicken Response

  • Vaccination Protocol: A hybrid protein was administered as a vaccine to chickens either orally or i.m. Alimentary secretions were collected , and specific antibodies were assayed by western blot analyses (Khoury et al., 1995).
  • Persistence: Seventy-two percent of the birds vaccinated orally with 1000 micrograms protein showed detectable antibodies against C jejuni flagellin in the excreta . None of the control birds produced detectable antibody to this antigen (Khoury et al., 1995).
  • Immune Response: Chickens orally immunized developed serum IgG and mucosal IgA responses against Campylobacter membrane proteins, as measured by an ELISA test. Protection experiments show that chicken immunization greatly reduces the ability of heterologous wild type C jejuni strain to colonize the bird cecum (Wyszynska et al., 2004).
  • Side Effects: No adverse side effects have been associated with this vaccine in chickens.
  • Challenge Protocol: For trials to demonstrate clearance of Campylobacter, groups of chickens were vaccinated with the hybrid protein at 2 and 4 wk of age and challenged at 3 wk with an excess of Cjejuni. The number of birds that remained colonized at 5 wk of age was significantly lower among the vaccinated birds than among controls (Khoury et al., 1995).
  • Efficacy: The nature of the antibody response to MOMP during in vivo infection is not well understood. Antibody responses elicited in Campylobacter-colonized chickens demonstrates that proteoliposomes restore reactivity to rabbit antibodies. Sera from naturally or experimentally infected chickens reacts weakly, suggesting that the chicken antibody response is predominantly directed against conformational epitopes. These observations provide direct evidence for conformation-dependent humoral responses induced by Campylobacter infection, demonstrate that C jejuni is immunogenic in its natural host and suggest that proteoliposomes may be potentially used for the evaluation of vaccines (Huang et al., 2007).
  • Description: This is a conserved immunodominant protein in this organism and a promising vaccine candidate because the protein is expressed in multiple Campylobacter isolates from both chicken and human hosts (Martin et al., 1999).

Ferret Response

  • Host Strain: Mustela putorius furo
  • Vaccination Protocol: Food was withheld prior to challenge. The vaccine dose was administered orally via a pediatric nasogastric tube. After 60 min, animals were administered paragoric i.p. to slow peristalsis. Drinking water was supplemented with tetracycline for three days prior to rechallenge to decrease the competing intestinal microflora (Burr et al., 2005).
  • Persistence: An oral regimen delivered on days 0, 3, 5, and 7 provided enhanced protection following oral homologous challenge delivered at Days 0 and 14. The percent protection observed was 100% in previously infected ferrets, 50% in a two-dose CWC group, and 89% in a four-dose CWC group. Protection was afforded through vaccination with sufficient inactivated whole cell vaccine, but protection was obtained regardless of the inclusion of the adjuvant LTR192G (Burr et al., 2005).
  • Immune Response: Antibodies generated during natural infection in ferrets by either strain 81-176 or strain VC167 appeared to react more strongly to glycosylated flagellins isolated from Campylobacter spp . than to unglycosylated , recombinant flagellins isolated from E coli . (Lee et al., 1999)
  • Side Effects: Following infection, animals were monitored three times daily for signs of diarrhea, dehydration, appetite and water consumption. Rectal swabs from each ferret were cultured for C. jejuni by direct plating on C. jejuni selective agar. At the appropriate time, blood samples were obtained by bleeding the animals from the jugular vein while under light anesthesia using acepromazine-ketamine. Collected sera were assayed for specific anti-Campylobacter immunoglobulin levels. At the conclusion of each experiment, animals were lightly anaesthetized with acepromazine-ketamine then euthanized by intracardiac injection of sodium pentobarbital (Burr et al., 2005).
  • Challenge Protocol: Food was withheld prior to challenge. Animals received ketamine plus acepromazine i.m. Following sedation, the vaccine or challenge dose was administered orally. Animals being fed live organisms were administered paragoric i.p. For secondary challenge the procedure was otherwise identical, except that NaHCO3 was delivered prior to challenge. In addition, drinking water was supplemented with tetracycline prior to rechallenge. All challenge doses were monitored by plate counts (Burr et al., 2005).
  • Efficacy: Ferrets show some conservation of protection against disease induced by Campylobacter. Upon rechallenge, homologous protection was 67-84%. Heterologous challenge resulted in 67-80% protection. These data indicate that the strain chosen for use in humans protects against disease caused by two of the major serotypes responsible for human disease (Burr et al., 2005).
  • Description: The strong IgG responses seen upon rechallenge of vaccinated or previously challenged animals may not be protective in themselves but could indicate the magnitude of other unmeasured antibody responses following immunization. Whatever the exact nature of the protective immune responses associated with the CWC vaccine, it is clear that the vaccine offers protection which may be relatively conserved among clinically important serotypes of Campylobacter (Burr et al., 2005).
References References
Martin et al., 1999: Martin PR, Mulks MH. Cloning and characterization of a gene encoding an antigenic membrane protein from Actinobacillus pleuropneumoniae with homology to ABC transporters. FEMS immunology and medical microbiology. 1999 Aug 15; 25(3); 245-54. [PubMed: 10459579].
Pawelec et al., 1997: Pawelec D, Rozynek E, Popowski J, Jagusztyn-Krynicka EK. Cloning and characterization of a Campylobacter jejuni 72Dz/92 gene encoding a 30 kDa immunopositive protein, component of the ABC transport system; expression of the gene in avirulent Salmonella typhimurium. FEMS immunology and medical microbiology. 1997 Oct; 19(2); 137-50. [PubMed: 9395059].
Wyszynska et al., 2004: Wyszynska A, Raczko A, Lis M, Jagusztyn-Krynicka EK. Oral immunization of chickens with avirulent Salmonella vaccine strain carrying C. jejuni 72Dz/92 cjaA gene elicits specific humoral immune response associated with protection against challenge with wild-type Campylobacter. Vaccine. 2004 Mar 29; 22(11-12); 1379-89. [PubMed: 15063560 ].
Baqar et al., 1995b: Baqar S, Applebee LA, Bourgeois AL. Immunogenicity and protective efficacy of a prototype Campylobacter killed whole-cell vaccine in mice. Infection and immunity. 1995 Sep; 63(9); 3731-5. [PubMed: 7642317].
Burr et al., 2005: Burr DH, Rollins D, Lee LH, Pattarini DL, Walz SS, Tian JH, Pace JL, Bourgeois AL, Walker RI. Prevention of disease in ferrets fed an inactivated whole cell Campylobacter jejuni vaccine. Vaccine. 2005 Jul 29; 23(34); 4315-21. [PubMed: 16005742 ].
Huang et al., 2007: Huang S, Sahin O, Zhang Q. Infection-induced antibodies against the major outer membrane protein of Campylobacter jejuni mainly recognize conformational epitopes. FEMS microbiology letters. 2007 Jul; 272(2); 137-43. [PubMed: 17521366].
Khoury et al., 1995: Khoury CA, Meinersmann RJ. A genetic hybrid of the Campylobacter jejuni flaA gene with LT-B of Escherichia coli and assessment of the efficacy of the hybrid protein as an oral chicken vaccine. Avian diseases. 1995 Oct-Dec; 39(4); 812-20. [PubMed: 8719215 ].
Lee et al., 1999: Lee LH, Burg E 3rd, Baqar S, Bourgeois AL, Burr DH, Ewing CP, Trust TJ, Guerry P. Evaluation of a truncated recombinant flagellin subunit vaccine against Campylobacter jejuni. Infection and immunity. 1999 Nov; 67(11); 5799-805. [PubMed: 10531231].
Martin et al., 1999: Martin PR, Mulks MH. Cloning and characterization of a gene encoding an antigenic membrane protein from Actinobacillus pleuropneumoniae with homology to ABC transporters. FEMS immunology and medical microbiology. 1999 Aug 15; 25(3); 245-54. [PubMed: 10459579].
Walker, 2005: Walker RI. Considerations for development of whole cell bacterial vaccines to prevent diarrheal diseases in children in developing countries. Vaccine. 2005 May 16; 23(26); 3369-85. [PubMed: 15837361].
Wyszynska et al., 2004: Wyszynska A, Raczko A, Lis M, Jagusztyn-Krynicka EK. Oral immunization of chickens with avirulent Salmonella vaccine strain carrying C. jejuni 72Dz/92 cjaA gene elicits specific humoral immune response associated with protection against challenge with wild-type Campylobacter. Vaccine. 2004 Mar 29; 22(11-12); 1379-89. [PubMed: 15063560 ].