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Vaccine Comparison

CVD 1204(pGA1-CS2) CVD 1204(pGA1-CS3) Recombinant SFL124-27 expressing S. dysenteriae type 1 O antigen S. dysenteriae 1 strain WRSd1 S. flexneri 2a LPS vaccine complexed with N. meningitidis proteosomes S. flexneri 2a strain CVD 1203 S. flexneri 2a strain CVD 1205 S. flexneri strain Sfl 124 S. sonnei strain WRSS1 Shigella sonnei virG/senA/senB mutant vaccine Shigella sonnei virG/senA/senB/msbB2 mutant vaccine
Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0000733
  • Type: Live, attenuated vaccine
  • AroA gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Preparation: This vaccine is a recombinant Shigella flexneri 2a strain CVD 1204 that expresses either Enterotoxigenic Escherichia coli (ETEC) CS2 Fimbriae (Altboum et al., 2001). Vaccines were prepared containing approximately 2 X 109 CFU of bacteria per syringe. The bacteria were grown on TSA-Congo red-guanine plates and harvested in PBS (Altboum et al., 2001).
  • Vaccine Ontology ID: VO_0000734
  • Type: Live, attenuated vaccine
  • Status: Licensed
  • Preparation: This vaccine is a recombinant Shigella flexneri 2a strain CVD 1204 that expresses either Enterotoxigenic Escherichia coli (ETEC) ETEC CS3 Fimbriae (Altboum et al., 2001). Vaccines were prepared containing approximately 2 X 109 CFU of bacteria per syringe. The bacteria were grown on TSA-Congo red-guanine plates and harvested in PBS (Altboum et al., 2001).
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0000674
  • Type: Recombinant vector vaccine
  • Preparation: S. flexneri SFL124-27 is a spontaneous rough mutant of the attenuated S. flexneri auxotrophic strain SFL124, which carries a deletion of the aroD gene. A recombinant strain SFL124-27 that expresses S. dysenteriae 1 O antigen was selected as the vaccine candidate (Klee et al., 1997).
  • Virulence: The vaccine was demonstrated to be immunogenic in animal models, leading to 47% full protection and 53% partial protection against challenge with the wild-type strain (Klee et al., 1997).
  • Vaccine Ontology ID: VO_0000676
  • Type: Live, attenuated vaccine
  • AroA gene engineering:
    • Type: Gene mutation
    • Description: WRSd1 was constructed from S. dysenteriae 1 strain 1617. The virG(icsA) deletion was constructed from a streptomycin-resistant mutant of 1617 by a filter mating procedures using a virG(icsA) deletion derivative, pvirG2. A colony that was invasive for HeLa cells and negative for the virG(icsA) gene by Southern blotting was grown anaerobically on plates containing chlorate for selection of resistant colonies that had lost the entire Shiga toxin gene. A virG(icsA) stxAB Str^r mutant selected from the chlorate plates was designated WRSd1 (Venkatesan et al., 2002).
    • Detailed Gene Information: Click Here.
  • Preparation: S. dysenteriae 1 strain WRSd1 is a attenuated vaccine that contains deletions of the virG(icsA) gene required for intercellular spreading and a 20-kb chromosomal region encompassing the Shiga toxin genes (stxAB) (Venkatesan et al., 2002). The vaccine was made with bacterial culture grown overnight on LB agar plates and harvested in PBS (Venkatesan et al., 2002).
  • Virulence: Attenuated
  • Description: Vaccination with WRSd1 conferred protection against challenge with each of three virulent S. dysenteriae 1 strains (Venkatesan et al., 2002).
  • Vaccine Ontology ID: VO_0000682
  • Type: Subunit vaccine
  • Antigen: The antigen for this acellular vaccine is purified Shigella flexneri LPS (Orr et al., 1993).
  • Preparation: Purified shigella LPS and group C serotype 2b N. meningitidis outer membrane proteins were mixed at a 1:1 ratio in PBS containing 1% Empigen. The mixture was dialyzed across a dialysis membrane against PBS. Samples of the purified LPS were mixed with PBS and sodium bicarbonate (Orr et al., 1993).
  • Virulence: Strong anamnestic responses were found , so acellular Shigella vaccines can protect against Shigella infection (Orr et al., 1993).
  • Vaccine Ontology ID: VO_0002920
  • Type: Recombinant vector vaccine
  • Antigen: The antigen for this vaccine is S. flexneri 2a strain 1203, a strain which contains deletions in chromosomal aroA and invasion plasmid virG (Noriega et al., 1994).
  • AroA gene engineering:
    • Type: Recombinant protein preparation
    • Description: Noriega et al. sequentially introduced precise deletion mutations into chromosomal gene aroA and plasmid gene virG in a wild-type S. flexneri 2a strain known to be virulent in volunteers. In order to do this, they constructed aroA and introduced several deletion cassetes (Noriega et al., 1994).
    • Detailed Gene Information: Click Here.
  • Virulence: Two 109-CFU orogastric doses (2 weeks apart) stimulated production of secretory immunoglobulin A antibodies to S.flexneri 2a and protected against conjunctival sac challenge with virulent S. flexneri 2a.
  • Vaccine Ontology ID: VO_0004143
  • Type: Recombinant vector vaccine
  • Antigen: The antigen for this vaccine is S. flexneri 2a strain CVD 1205, which carries deletion mutations in the guaB-A operon and in the virG gene (also called icsA) (Noriega et al., 1996).
  • GuaB gene engineering:
    • Type: Recombinant protein preparation
    • Description: CVD 1205 is made through deletion of virG from CVD 1204. Producing strain CVD 1205 took many steps and began with construction of the guaB-A deletion cassette pFM726A. In the construction of the guaB-A deletion cassette, DNA segments that included the 59 terminus of guaB and the 39 terminus of guaA were amplified (from S. flexneri 2a strain 2457T genomic DNA) and fused by PCR, originating the guaB-A allele. With the internal primers (primers 2 and 3) was introduced an in-frame stop sign upstream of two unique restriction sites that were added for the future introduction of foreign genes into the chromosomal DguaB-A allele. The external primers (primers 1 and 4) were designed to introduce unique restriction sites that were used to clone the guaB-A allele into the temperature-sensitive, pSC101-based suicide plasmid pFM307A, originating pFM726A. The same external primers were used to amplify the wild-type guaB-A operon (from strain 2457T), which was subsequently cloned in pGEM-T, yielding pGEM::gua, and in pFM307A, yielding pFM215A. Suicide cassette-driven deletion mutations and repair of the same. Deletion cassette pFM726A was used to introduce the deletion mutation into wild-type S.flexneri 2a strain 2457T by homologous recombination as described in previously published method, yielding strain CVD 1204. Plasmid FM215A was used to repair the deletion mutation by homologous recombination of the chromosomal guaB-A allele in strain CVD 1204 for the wild-type operon contained in the suicide plasmid.
      A second deletion mutation on the virulence gene virG was performed with a previously described suicide deletion cassette (pDvirG) and methods (24), yielding strain CVD 1205. The deletion mutation corresponds to 900 bases representing amino acids 341 to 640 of the 120-kDa VirG protein. The specific engineered site for this deletion in the protein represents a highly hydrophobic, poorly antigenic portion of the molecule genic index (Noriega et al., 1996).
    • Detailed Gene Information: Click Here.
  • Preparation: Overnight cultures of guaB-A virG S. flexneri 2a strain CVD 1205 and HS strains were harvested and resuspended PBS to an optical density at 600 nm of 0.5 (equivalent to 5 3 108 CFU/ml) and concentrated by centrifugation to the desired concentration (Noriega et al., 1996).
  • Virulence: Upon Sereny test challenge with wild-type S. flexneri 2a, CVD 1205-vaccinated animals were significantly protected against keratoconjunctivitis (Noriega et al., 1996).
  • Vaccine Ontology ID: VO_0000673
  • Type: Live, attenuated vaccine
  • Antigen: The antigen for this vaccine is Sfl 124, which is an S. flexneri Y strain. This strain was derived through the strain Sfl 114 (Hartman et al., 1991).
  • AroD gene engineering:
    • Type: Gene mutation
    • Detailed Gene Information: Click Here.
  • Preparation: This vaccine is derived from S. flexneri strain SFl 114, which was constructed by making the virulent parent strain Sfl1 an aroD mutant. This rendered it dependent on aromatic metabolites not available in mamillian tissues. The tetracycline resistance properties of Sfl 114 were removed, and this resulting vacccine was called SFl 124 (Hartman et al., 1991). The vaccines were prepared in a lactose-phosphate-glutamate medium with dextran 10 added, then lypholized. All vaccines were rehydrated from the lypholized state with distilled water and diluted with phosphate-buffered saline. Each vaccine contained 3 x 108 to 5 x 108 organisms, and contained approximately 0.05 ml of cell suspension (Hartman et al., 1991).
  • Virulence: Homologous protection occurred after the initial infection with the virulent strain (Hartman et al., 1991).
  • Vaccine Ontology ID: VO_0000678
  • Type: Recombinant vector vaccine
  • AroA gene engineering:
    • Type: Gene mutation
    • Description: WRSS1 was constructed from the Mosely strain of S. sonnei. A parent strain was selected that exhibited stability of the form I colonial phenotype, then sacB suicide vector pCVD422 was used to replace the wild-type virG allele with virG possessing a 212-bp deletion. In preclinical experiments (Kotloff et al., 2002).
    • Detailed Gene Information: Click Here.
  • Preparation: WRSS1 is a stable S. sonnei mutant with a deletion in virG (Kotloff et al., 2002). The final composition of the vaccine consisted of 3.7 x 1010 CFU of WRSS1 per vial in PBS containing 7.5% dextran T10, 2% sucrose, and 1.5% glycerol as a cryopreservative (Kotloff et al., 2002).
  • Virulence: WRSS1 vaccine is remarkably immunogenic in doses ranging from 103 to 106 CFU (Kotloff et al., 2002).
  • Product Name: WRSs2
  • Type: Live, attenuated vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Guinea pig
  • virG gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • senA gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • senB gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • Immunization Route: Oral immunization
  • Product Name: WRSs3
  • Type: Live, attenuated vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Guinea pig
  • virG gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • senA gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • senB gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • msbB2 gene engineering:
    • Type: Gene mutation
    • Description: This virG/senA/senB/msbB2 mutant is from Shigella sonnei (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • Immunization Route: Oral immunization
Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response

Human Response

  • Vaccination Protocol: Fasting volunteers ingested 2g of sodium bicarbonate buffer dissolved in 150 ml of water, followed 1 min later by 30 ml of water containing the assigned vaccine dose or no vaccine (placebo) (Kotloff et al., 2002).
  • Immune Response: Vaccination elicited vigorous IgA ASC anti-LPS responses in all of the groups. ASC responses were less common and smaller in magnitude in the IgG anti-LPS assay and in both anti-Ipa assays. Geometric mean peak postvaccination anti-LPS serum IgG and fecal IgA titers were also robust. Most of the subjects exhibited a fourfold rise in serum and/or fecal anti-LPS antibody titers. Whereas the anti-LPS IgA ASC and fecal antibody responses tended to increase with the dose, a similar trend was not apparent in serum antibody responses. Postvaccination antigen-specific proliferative responses and increases in IL-10 production were not seen (Kotloff et al., 2002).
  • Side Effects: Side effects included fever, loose stools or aysmptomatic diarrhea, and mild cramps (Kotloff et al., 2002).
  • Description: This is a Phase I study.

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: To assess whether the recombinant O antigen was immunogenic and to compare the immunogenicity with that of wild-type S. dysenteriae 1, groups of five six-week-old female BALB/c mice were immunized on days 0, 14, and 28 by intraperitoneal injection of 0.2 x 108 to 1.0 x 108 heat-killed bacteria suspended in PBS. Two weeks after the last immunization, the mice were sacrificed, blood samples were collected, and antibody titers against LPS of S. dysenteriae 1 were determined by enzyme-linked immunosorbent assay (Klee et al., 1997).
  • Persistence: The antibody titers of mice immunized with S. dysenteriae 1 or S. flexneri SFL124-27::Tn(rfp-rfb)-39 were significantly higher than the titers in the nonimmunized group and in mice immunized with the rough strain SFL124-27. This indicates the synthesis of enough surface-displayed LPS molecules to trigger a specific immune response, a prerequisite for a vaccine strain (Klee et al., 1997).
  • Challenge Protocol: No challenge was done on the mice, as this was only to assess the immunogenicity of the recombinant O antigen.

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: BALB/c mice were were immunized either orally or intranasally with 100 miroliters of PBS containing 100 micrograms of LPS with 0.2 M sodium bicarbonate that was given either alone or complexed with 100 micrograms of proteosomesusing a bent metal tube. For intranasal immunization, 25 micrograms of LPS either alone or complexed with 10 micrograms of proteosomeswas slowly placed into one or both of the nares. The control group recieved diluent without antigen (Orr et al., 1993).
  • Immune Response: Vaccination produced high levels of anti-LPS IgG and anti-LPS IgA in mice immunized two or three times (Orr et al., 1993).
  • Challenge Protocol: Mice were challenged with LPS two weeks after their last immunization (Orr et al., 1993).
  • Efficacy: All mice in control groups were infected. 14 out of 19 and 11 out of 16 mice were protected from severe infection after intranasal or oral vaccination. 9 out of 16 animals were protected from any illness (Orr et al., 1993).

Monkey Response

  • Host Strain: Rhesus (Macaca mulatta)
  • Vaccination Protocol: Five rhesus monkeys were a part of the study. 20 ml of saturated sodium bicarbonate was administered intragastrically through a pediatric stomach tube fitted over a disposable plastic syringe, followed by 20 ml
    of the bacterial inoculum (109 CFU) of WRSd1) in water. The inoculum was obtained by hydrating the lyophilized vaccine product (Venkatesan et al., 2002).
  • Persistence: Two of five monkeys excreted the vaccine strain in stool cultures for 48 h after the administration of the vaccine, as evidenced by transparent colonies on Hektoen agar plates (Venkatesan et al., 2002).
  • Immune Response: Four monkeys showed a 2-to 3-fold rise in serum immunoglobulin G (IgG) response to S. dysenteriae 1 LPS at day 7 or day 14 and one monkey showed a 3-fold rise in serum IgA responseto S. dysenteriae LPS. None of the monkeys had a detectable rectal lavage sample immune response (Venkatesan et al., 2002).
  • Side Effects: Not noted.
  • Challenge Protocol: Monkeys were challenged with 2 x 1010 CFU of SC602 vaccine (Venkatesan et al., 2002).
  • Efficacy: The immune response generated was higher than that observed in monkeys given 6 x 109 CFU of the cGMP product (Venkatesan et al., 2002).

Guinea pig Response

  • Vaccination Protocol: Guinea pigs were inoculated intranasally on days 1 and 15 with approximately 2 x 109 CFU of bacteria. Five groups of animals were inoculated: group 1 was immunized with CVD 1204; group 2 received CVD 1204-CS3; group 3 received CVD 1204-CS2; group 4 received a mixture of CVD 1204-CS3 plus CVD 1204-CS2; and group 5, serving as a placebo control, received 2 x 1010 CFU of E. coli HS. Groups 1 to 4 contained 5 animals each, whereas group 5 had 15 guinea pigs. Sera were obtained on days 0, 14, and 30 by anterior vena cava puncture of anesthetized animals. Tears were collected on the same days by lacrimal stimulation (Altboum et al., 2001).
  • Persistence: CVD 1204-CS3 or CVD 1204-CS3 and CVD 1204-CS2 mixed yielded titers that were boosted to even higher levels following the second dose. Antifimbrial titers were comparable in groups receiving a single strain or a mixture of strains Anti-CS3 IgG titers ranged in group 2 from 51,200 to 204,800 and in group 4 from 12,800 to 204,800. Anti-CS2 IgGtiters ranged in group 3 from 100 to 1,600 and in group 4 from 100 to 1,600. Anti-Shigella LPS IgG titers ranged in group 1 from 400 to 1,600, in group 2 from 800 to 3,200, in group 3 from 400 to 3,200, and in group 4 from 100 to 200 (Altboum et al., 2001).
  • Immune Response: Following a single dose of any CVD 1204 inoculum, half of the animals responded with anti-Shigella LPS mucosal IgA, whereas three-fourths of the animals responded with anti-Shigella LPS serum IgG. All animals immunized with CVD 1204(pGA1-CS2) (groups 3 and 4) developed anti-CS2 mucosal IgA and serum IgG following a single dose. Two immunizations were required to elicit anti-CS2 serum IgG responses in all animals (Altboum et al., 2001).
  • Side Effects: Conjuntivitis (Altboum et al., 2001).
  • Challenge Protocol: The guinea pigs were challenged 21 days following the second dose with 10 micoliters containing 108 CFU of wild-type S. flexneri 2a 2457T in the conjunctival sac (Altboum et al., 2001).
  • Efficacy: Upon Sereny test challenge with wild-type S. flexneri 2a, all 15 animals vaccinated intranasally with the placebo strain of E. coli HS developed severe keratoconjunctivitis. In contrast, none of the animals (5 per group) immunized with either native CVD 1204 or CVD 1204 expressing ETEC fimbriae developed severe keratoconjunctivitis (P < 0.01). One animal in the group immunized with CVD 1204(pGA1-CS2) had a score of 1 on day 3. One animal in the group immunized with CVD 1204(pGA1-CS3) had a score of 2 on days 3 and 4 (Altboum et al., 2001).
  • Host IgA response
    • Description: Following a single dose of any CVD 1204 inoculum, half of the animals responded with anti-Shigella LPS mucosal IgA. After second immunization, the most dramatic difference in IgA titers between pre and post immunization was seen in guinea pigs (Altboum et al., 2001).
    • Detailed Gene Information: Click Here.
  • Host IgG Fc receptor II response
    • Description: Following a single dose of any CVD 1204 inoculum, three-fourths of the animals responded with anti-Shigella LPS serum IgG. A dramatic increase in IgG titers between pre and post immunized guinea pigs was seen after the second immunization (Altboum et al., 2001).
    • Detailed Gene Information: Click Here.

Guinea pig Response

  • Vaccination Protocol: Guinea pigs were inoculated intranasally on days 1 and 15 with approximately 2 x 109 CFU of bacteria. Five groups of animals were inoculated: group 1 was immunized with CVD 1204; group 2 received CVD 1204-CS3; group 3 received CVD 1204-CS2; group 4 received a mixture of CVD 1204-CS3 plus CVD 1204-CS2; and group 5, serving as a placebo control, received 2 x 1010 CFU of E. coli HS. Groups 1 to 4 contained 5 animals each, whereas group 5 had 15 guinea pigs. Sera were obtained on days 0, 14, and 30 by anterior vena cava puncture of anesthetized animals. Tears were collected on the same days by lacrimal stimulation (Altboum et al., 2001).
  • Persistence: CVD 1204-CS3 or CVD 1204-CS3 and CVD 1204-CS2 mixed yielded titers that were boosted to even higher levels following the second dose. Antifimbrial titers were comparable in groups receiving a single strain or a mixture of strains Anti-CS3 IgG titers ranged in group 2 from 51,200 to 204,800 and in group 4 from 12,800 to 204,800. Anti-CS2 IgGtiters ranged in group 3 from 100 to 1,600 and in group 4 from 100 to 1,600. Anti-Shigella LPS IgG titers ranged in group 1 from 400 to 1,600, in group 2 from 800 to 3,200, in group 3 from 400 to 3,200, and in group 4 from 100 to 200 (Altboum et al., 2001).
  • Immune Response: Animals immunized with Shigella expressing CS3 developed serum antibodies that agglutinated Shigella as well as an ETEC strain bearing the homologous fimbriae (Altboum et al., 2001).
  • Side Effects: Conjuntivitis (Altboum et al., 2001).
  • Challenge Protocol: The guinea pigs were challenged 21 days following the second dose with 10 micoliters containing 108 CFU of wild-type S. flexneri 2a 2457T in the conjunctival sac (Altboum et al., 2001).
  • Efficacy: Upon Sereny test challenge with wild-type S. flexneri 2a, all 15 animals vaccinated intranasally with the placebo strain of E. coli HS developed severe keratoconjunctivitis. In contrast, none of the animals (5 per group) immunized with either native CVD 1204 or CVD 1204 expressing ETEC fimbriae developed severe keratoconjunctivitis (P < 0.01). One animal in the group immunized with CVD 1204(pGA1-CS3) had a score of 2 on days 3 and 4 (Altboum et al., 2001).

Guinea pig Response

  • Host Strain: Dunkin Hartley
  • Vaccination Protocol: The Sereny test with guinea pigs was performed as follows: Congo red-positive colonies of the Shigella vaccine candidate were diluted in PBS, and 25 ml was applied to the conjunctival sacs of 15 adult Dunkin Hartley guinea pigs at days 0, 7, 14, and 21 with an average of four immunizing doses, 3.7 x 109 bacteria per eye (Klee et al., 1997).
  • Persistence: Vaccination led to statistically significant amounts of antibodies against S. Dysenteriae (Klee et al., 1997).
  • Immune Response: None of the four immunization doses given to the 15 guinea pigs resulted in detectable keratoconjunctivitis, thereby demonstrating the safety of this prototype vaccine candidate in this animal model (Klee et al., 1997).
  • Challenge Protocol: At day 35, the animals were challenged with 108 bacteria of the virulent strain S. dysenteriae 1 W30864 per eye, and the symptoms of keratoconjunctivitis were recorded for 6 days. As a control, another group of 14 nonvaccinated guinea pigs was also challenged with the virulent strain at day 35 (Klee et al., 1997).
  • Efficacy: In the vaccinated group, 7 of 15 animals developed no signs of keratoconjunctivitis (47% full protection), and in the other 8 animals, later development of the disease was observed (53% partial protection), resulting in a combined protection of 100%, whereas in the nonvaccinated group 71% of challenged animals rapidly developed severe disease.The vaccinated animals developed symptoms of keratoconjunctivitis later than animals of the control group, and the absolute number of guinea pigs showing strong reactions, or purulent inflammation of the whole eye, was significantly reduced (Klee et al., 1997).

Guinea pig Response

  • Vaccination Protocol: The eyes of 12 guinea pigs were inoculated with 108 CFU of WRSd1. The eyes were observed for 5 to 6 days for evaluation of the Sereny reaction. When eyes were immunized for efficacy studies of vaccine candidates, mmunization was carried out twice at 2-week intervals (Venkatesan et al., 2002).
  • Immune Response: Not noted.
  • Side Effects: Side effects included purulence and conjunctivitis in some of the eyes tested (Venkatesan et al., 2002).
  • Challenge Protocol: Four weeks after the last immunization, animals were challenged at the same dose using one of three virulent S. dysenteriae 1 strains: 1617, the parent strain of WRSd1; Ubon 378; and Shiga (Venkatesan et al., 2002).
  • Efficacy: WRSd1 protected fully against challenge by Ubon 378 and Shiga. At the single dose used for immunization in this experiment, WRSd1 protected partially against the parent strain 1617 (Venkatesan et al., 2002).

Guinea pig Response

  • Host Strain: DH
  • Vaccination Protocol: Anesthetized guinea pigs were immunized. Orally, they each received 200 microliters of PBS with sodium bicarbonate and 200 micrograms of the LPS complex. Intranasally, each guinea pig received 50 microliters of PBS with 40 micrograms of the LPS complex (Orr et al., 1993).
  • Immune Response: Guinea pig titers proved strong anti-LPS IgG antibodies and anti-LPS IgA antibodies (Orr et al., 1993).
  • Challenge Protocol: The conjunctival sac of one eye of each animal was inoculated with 30 microliters of a suspension containing and estimeted 108 of homologous bacteria (Orr et al., 1993).
  • Efficacy: The vaccines elicited an in vivo protection against homologous bacteria (Orr et al., 1993).

Guinea pig Response

  • Host Strain: Hartley
  • Vaccination Protocol: 33 guinea pigs were randomly allocated to receive orogastrically 10 CFU of CVD 1203 or control strain E. coli HS. A second immunization was given 15 days later. Tears were collected from 10 guinea pigs (5 immunized with CVD 1203 and 5 immunized with E. coli HS) on days 7, 14, and 21 after the first orogastric dose to measure secretory immunoglobulin A (S-IgA) antibodies against S. flexneri 2a LPS by enzyme-linked immunosorbent assay (Noriega et al., 1994).
  • Immune Response: Immunization with CVD 1203 clearly stimulated production of S-IgA antibodies to S. flexneri 2a LPS in tears (Noriega et al., 1994).
  • Side Effects: Not noted.
  • Challenge Protocol: On the 28th day after the first immunization, 16 vaccinated guinea pigs and 17 control guinea pigs were challenged with 5 x 107 CFU of the wild-type 2457T strain in 10 ,ul (Noriega et al., 1996).
  • Efficacy: Full-blown keratoconjunctivitis developed in 16 of 17 control animals orogastrically vaccinated with the placebo (a 94% attack rate), in contrast to only 3 of 16 guinea pigs immunized with two spaced orogastric doses of CVD 1203 (a 19% attack rate) (Noriega et al., 1994).
  • Host IgA response
    • Description: Immunization with CVD 1203 clearly stimulated production of IgA antibodies to S. flexneri 2a LPS in tears. A significant increase was seen 14 days after immunization, which was compared to the static control immunization with E. coli HS (Noriega et al., 1994).
    • Detailed Gene Information: Click Here.

Guinea pig Response

  • Host Strain: Hartley
  • Vaccination Protocol: Randomized, nonpreconditioned Hartley guinea pigs were given intranasally 100 ml of bacterial suspension containing 109 CFU as described previously. A booster dose was administered 14 days later in the identical manner (Noriega et al., 1996).
  • Persistence: At 72 h postinoculation, the (blinded) observer grading the inflammatory response in the guinea pigs could not distinguish the inoculated eye from the noninoculated one in any of the animals that received the attenuated mutant CVD 1205, while all animals that received wild-type strain 2457T had full-blown purulent keratoconjunctivitis (Noriega et al., 1996).
  • Immune Response: The serum antibody response was more delayed, since no serum IgG or IgA anti-Shigella LPS was detected after the first immunization. However, by day 2 animals immunized with CVD 1205 had specific anti-S. flexneri 2a LPS IgA (i.e., 78-fold rise in GMT) and IgG (i.e., 60-fold rise in GMT) titers that were highly significant with respect to those obtained at day 0 in the same guinea pigs or at days 0 and 28 in the strain HS controls (Noriega et al., 1996).
  • Side Effects: No side effects were noted.
  • Challenge Protocol: Protection of guinea pigs against wild-type challenge. On day 28 after the first immunization, the 16 guinea pigs that had received CVD 1205 or placebo were challenged with 3 x 107 CFU of wild-type S. flexneri 2a strain 2457T in 10 ml of PBS (Noriega et al., 1996).
  • Efficacy: Full-blown purulent keratoconjunctivitis developed in five of seven control animals vaccinated with placebo (71% attack rate) versus none of the eight guinea pigs immunized with two spaced intranasal doses of CVD 1205 (Noriega et al., 1996).

Guinea pig Response

  • Host Strain: Hartley
  • Vaccination Protocol: Male Hartley guinea pigs were innoculated. Each guinea pig received 0.05 ml of cell suspension in the conjunctival sac of each eye with a dropper. Immunization occurred on days 0,1,14, and 15. Follwing vaccination, guinea pigs were evaluated daily for the development of keroconjunctivitis (Hartman et al., 1991).
  • Persistence: Not noted.
  • Immune Response: Sera obtained from guinea pigs reacted with IpA proteins and showed no reaction to the pUC19 control (Hartman et al., 1991).
  • Side Effects: The only side effect was keroconjunctivitis (Hartman et al., 1991).
  • Challenge Protocol: Animals were challenged with the same strain 4, 7, or 13 weeks after infection (Hartman et al., 1991).
  • Efficacy: The attack rate following previous infection was less than 20%. Protection was still more than 80% 7 weeks postinfection (Hartman et al., 1991).

Guinea pig Response

  • Vaccination Protocol: The protective efficacy and immunogenicity of WRSS1 were measured with the guinea pig keratoconjunctivitis model. Ocular immunization with 3 × 108 to 4 × 108 CFU of WRSS1/eye on days 0 and 14.
  • Challenge Protocol: Four weeks after the last immunization, both the immunized animals and the unimmunized control animals were challenged with 4 × 108 CFU of virulent S. sonnei 53G/eye.
  • Efficacy: In animals immunized with WRSS1 grown from overnight plate cultures, 13 of 16 eyes showed no signs of disease (83% complete protection), while 3 eyes showed mild conjunctivitis (17% partial protection). When reconstituted lyophilized cultures were used, 10 of 16 eyes did not develop disease (63% complete protection), while 4 eyes developed mild disease (25% partial protection). In both cases, protection against challenge was significant by the Fisher exact test (P < 0.001), and there was no significant difference in the levels of protection conferred by the two formulations.
  • Description: WRSS1 was found to be both immunogenic and protective in the guinea pig keratoconjunctivitis model (Hartman and Venkatesan, 1998).
  • Host IgA response
    • Description: WRSS1 elicits vigorous anti-LPS IgA ASC and serum IgA and IgG antibody responses that are similar in magnitude to those elicited by other strains that prevented illness. IgA responses were significantly greater 7 to 10 days post inoculation in those that received WRSS1 as opposed to the placebo (Kotloff et al., 2002).
    • Detailed Gene Information: Click Here.
  • Host IgG response
    • Description: WRSS1 elicits vigorous anti-LPS IgA ASC and serum IgA and IgG antibody responses that are similar in magnitude to those elicited by other strains that prevented illness. IgG responses were significantly greater 7 to 10 days post inoculation in those that received WRSS1 as opposed to the placebo (Kotloff et al., 2002).
    • Detailed Gene Information: Click Here.

Guinea pig Response

  • Persistence: A virG, senA, and senB mutant is attenuated in guinea pigs (Barnoy et al., 2010).
  • Efficacy: A virG, senA, and senB mutant induces significant protection in guinea pigs from challenge with wild type Shigella sonnei (Barnoy et al., 2010).
  • Host IgA response
    • Description: Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • Host IgG Fc receptor II response
    • Description: Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.

Guinea pig Response

  • Persistence: A virG, senA, senB, and msbB2 mutant is attenuated in guinea pigs (Barnoy et al., 2010).
  • Efficacy: A virG, senA, senB, and msbB2 mutant induces protection in guinea pigs from challenge with wild type Shigella sonnei (Barnoy et al., 2010).
  • Host IgA response
    • Description: Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
  • Host IgG Fc receptor II response
    • Description: Serum GMTs of LPS-specific and Invaplex-specific IgG and IgA were very similar across the three vaccine candidates, indicating that WRSs2 and WRSs3 elicited comparable levels of humoral immune responses in guinea pigs as WRSS1. Antibodies were measured days 0, 7, and 14 after inoculation as well as 2 weeks after challenge. Antibody levels increased greatly between days 0 and 28 (Barnoy et al., 2010).
    • Detailed Gene Information: Click Here.
References References References References References References References References References References References
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Altboum et al., 2001: Altboum Z, Barry EM, Losonsky G, Galen JE, Levine MM. Attenuated Shigella flexneri 2a Delta guaBA strain CVD 1204 expressing enterotoxigenic Escherichia coli (ETEC) CS2 and CS3 fimbriae as a live mucosal vaccine against Shigella and ETEC infection. Infection and immunity. 2001; 69(5); 3150-3158. [PubMed: 11292735].
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Noriega et al., 1996: Noriega FR, Losonsky G, Lauderbaugh C, Liao FM, Wang JY, Levine MM. Engineered deltaguaB-A deltavirG Shigella flexneri 2a strain CVD 1205: construction, safety, immunogenicity, and potential efficacy as a mucosal vaccine. Infection and immunity. 1996; 64(8); 3055-3061. [PubMed: 8757833].
Hartman et al., 1991: Hartman AB, Powell CJ, Schultz CL, Oaks EV, Eckels KH. Small-animal model to measure efficacy and immunogenicity of Shigella vaccine strains. Infection and immunity. 1991; 59(11); 4075-4083. [PubMed: 1937767].
Hartman and Venkatesan, 1998: Hartman AB, Venkatesan MM. Construction of a stable attenuated Shigella sonnei DeltavirG vaccine strain, WRSS1, and protective efficacy and immunogenicity in the guinea pig keratoconjunctivitis model. Infection and immunity. 1998; 66(9); 4572-4576. [PubMed: 9712824].
Kotloff et al., 2002: Kotloff KL, Taylor DN, Sztein MB, Wasserman SS, Losonsky GA, Nataro JP, Venkatesan M, Hartman A, Picking WD, Katz DE, Campbell JD, Levine MM, Hale TL. Phase I evaluation of delta virG Shigella sonnei live, attenuated, oral vaccine strain WRSS1 in healthy adults. Infection and immunity. 2002; 70(4); 2016-2021. [PubMed: 11895966].
Barnoy et al., 2010: Barnoy S, Jeong KI, Helm RF, Suvarnapunya AE, Ranallo RT, Tzipori S, Venkatesan MM. Characterization of WRSs2 and WRSs3, new second-generation virG(icsA)-based Shigella sonnei vaccine candidates with the potential for reduced reactogenicity. Vaccine. 2010; 28(6); 1642-1654. [PubMed: 19932216].
Barnoy et al., 2010: Barnoy S, Jeong KI, Helm RF, Suvarnapunya AE, Ranallo RT, Tzipori S, Venkatesan MM. Characterization of WRSs2 and WRSs3, new second-generation virG(icsA)-based Shigella sonnei vaccine candidates with the potential for reduced reactogenicity. Vaccine. 2010; 28(6); 1642-1654. [PubMed: 19932216].