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Vaccine Comparison

S. aureus ClfA Protein Vaccine S. aureus CNA Protein Vaccine S. aureus DNA vaccine encoding Efb, FnbpA, ClfA, Cna S. aureus DNA Vaccine encoding PBP2a Protein S. aureus DNA vaccine pClfaSrtD13 S. aureus FnbA Protein Vaccine S. aureus IsdB subunit vaccine (V710) Staphylococcus aureus aroA mutant vaccine
Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0004047
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Recombinant ClfA protein (Josefsson et al., 2001).
  • ClfA gene engineering:
    • Type: Recombinant protein preparation
    • Description: Expression and purification of recombinant proteins.Vector pCF40 expressed rClfA truncate rClfA40‐559 (Josefsson et al., 2001).
    • Detailed Gene Information: Click Here.
  • Adjuvant: complete Freunds adjuvant
  • Immunization Route: subcutaneous injection
  • Vaccine Ontology ID: VO_0004048
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: a recombinant fragment of CNA protein (Nilsson et al., 1998).
  • cna gene engineering:
    • Type: Recombinant protein preparation
    • Description: CNA fragments were expressed in E. coli and then purified (Nilsson et al., 1998).
    • Detailed Gene Information: Click Here.
  • Adjuvant: complete Freunds adjuvant
  • Immunization Route: subcutaneous injection
  • Vaccine Ontology ID: VO_0004542
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • Antigen: fibrinogen binding protein (Efb), fibronectin-binding protein A (FnbpA), clumping factor A (ClfA) and collagen-binding protein (Cna) from S. aureus strain 1706 (Castagliuolo et al., 2006)
  • ClfA gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • cna gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • efb gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • fnbA gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Vector: pcDNA3.1 (Castagliuolo et al., 2006)
  • Immunization Route: intranasal immunization
  • Vaccine Ontology ID: VO_0004192
  • Type: DNA vaccine
  • Status: Research
  • MecA gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Vector: pCI-Neo Mammalian Expression Vector (Promega)
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004541
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • Antigen: Clumping factor A (Clfa), fibronectin binding protein A (FnBPA) and the enzyme Sortase (Srt) from strains “Newman” or “8325-4” (Gaudreau et al., 2007)
  • ClfA gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Vector: pCI (Gaudreau et al., 2007)
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004049
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Fibronectin binding domain of FnbA protein
  • fnbA gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: complete Freunds adjuvant
  • Immunization Route: subcutaneous injection
  • Product Name: V710
  • Vaccine Ontology ID: VO_0004220
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Purified IsdB protein
  • Adjuvant: amorphous aluminum hydroxyphosphate sulfate adjuvant (AAHSA)
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0002797
  • Type: Live, attenuated vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • aroA gene engineering:
    • Type: Gene mutation
    • Description: This aroA mutant is from Staphylococcus aureus (Buzzola et al., 2006).
    • Detailed Gene Information: Click Here.
  • Immunization Route: Intramammary immunization
Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response

Mouse Response

  • Host Strain: NMRI
  • Vaccination Protocol: Purified rClfA region A, comprising residues 40–559 (rClfA40‐559), and BSA (Sigma Chemical) were dissolved in physiologic saline and were emulsified 1:1 in Freund's complete adjuvant (Difco Laboratories). In total, 200 μL of the emulsion containing 30 μg of protein was injected subcutaneously (sc) on day −21 ( /group). Booster immunization with 30 μg of protein in physiologic saline:Freund's incomplete adjuvant 1:1 sc was done on day −10 (Josefsson et al., 2001).
  • Challenge Protocol: On day 0, the mice were challenged iv with 1.6 x 107 cfu/mouse of wild‐type S. aureus strain Newman (Josefsson et al., 2001).
  • Efficacy: Mice immunized with rClfA40‐559 had less severe arthritis than did the control BSA‐immunized group throughout the experiment. Both the severity of synovitis and the extent of joint destruction were markedly less pronounced in mice immunized with rClfA40‐559 than in the BSA control group (Josefsson et al., 2001).

Mouse Response

  • Host Strain: NMRI
  • Vaccination Protocol: Purified recombinant collagen adhesin fragments M17, M31, M55, and BSA (Sigma Chemical Co.) were dissolved in PBS and emulsified 1:1 in Freund’s complete adjuvant 200 μl of the emulsion containing 100 μg of protein was injected subcutaneously (s.c.) on day -31. Booster immunizations (s.c.; 100 μg protein in PBS) were performed 15 and 24 d after the initial vaccination (Nilsson et al., 1998).
  • Challenge Protocol: After the final boost, mice were inoculated intravenously (i.v.) with S. aureus (Nilsson et al., 1998).
  • Efficacy: At 14 d after inoculation, mortality in the collagen adhesin-vaccinated group was only 13%, compared with 87% in the control antigen immunized group (Nilsson et al., 1998).

Mouse Response

  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: Intranasal immunization with a pDNA mixture coding the four adhesins triggered significant levels of specific serum and mucosal Ig that inhibited S. aureus adhesion to cow mammary gland epithelial cells in vitro. Splenocytes of immunized mice challenged in vitro with S. aureus extracts showed a strong proliferative response (Castagliuolo et al., 2006).
  • Efficacy: In non immune mice or mice injected with empty vectors, a large number of bacteria was recovered from the mammary glands. Whereas, in mice immunized with the genetic vaccine coding the four S. aureus adhesins, the amount of bacteria recovered from the mammary glands was significantly decreased (Castagliuolo et al., 2006).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Three days before the first immunization, bupivacain chloridrate 0.5% was injected at a dose of 2.5 μl/g of animal weight in the left quadriceps muscle. For DNA vaccination, three intramuscular injections with 10 μg of plasmid pCI-Neo-mecA or pCI-Neo only (negative control) diluted in 50 μl of sterile PBS were given at 2 weeks intervals into the left quadriceps muscle of mice (Senna et al., 2003).
  • Challenge Protocol: To assess the immune response against MRSA, mice immunized with pCI-Neo and pCI-Neo-mecA were challenged with MRSA (MRSA HPS-03). Mice received a sublethal dose of 2.0×106 cfu intraperitonially daily for 7 days. A non-immunized group receiving the same bacterial dose was included as positive control.
  • Efficacy: After challenge, the number of bacteria from kidneys from immunized and non-immunized mice was determined. Kidneys from immunized mice had 1000 times less on bacteria than the positive controls (non-immunized mice) (Senna et al., 2003).

Mouse Response

  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: All animals produced a mixed Th1 and Th2 response including functional antigen-specific, mostly IgG2a antibodies, sustained production of IFN-gamma and a predominantly CD8+ T-cell response (Gaudreau et al., 2007).
  • Efficacy: Fourteen days after challenge, 70% of the vaccinated mice had survived as compared to only 15% of the control mice and after 21 days, the figures were 55% survival for the vaccinated as compared to 15% survival of the control group. However, signs of arthritis were observed in all the infected mice whether vaccinated or not (Gaudreau et al., 2007).

Mouse Response

  • Host Strain: BSVS
  • Vaccination Protocol: Mice were vaccinated subcutaneously in the neck region with 20 μg of the antigens emulsified with complete Freund's adjuvant (primary vaccination) a few days after mating. Booster doses were given after 14 days with the same amount of immunogen, but emulsified with incomplete Freund's adjuvant (Mamo et al., 1994).
  • Challenge Protocol: Mice were challenged 18-21 days after the booster dose by intramammary inoculation (mouse mastitis model) 23. Briefly, mice were anaesthetized using ether inhalation, the teat tips were aseptically removed and a 0.1 ml bacterial suspension (1 x l0^6 c.f.u, m1-1) was inoculated into the left quarter (L-4) and right quarter (R-4) mouse mammary glands (Mamo et al., 1994).
  • Efficacy: Vaccination of mice with recombinant FnBP resulted in significant protection against challenge with S. aureus (Mamo et al., 1994).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Groups of 20 BALB/c or ICR mice were immunized three times with IsdB (20 μg per dose) formulated with amorphous aluminum hydroxyphosphate sulfate adjuvant (AAHSA) (450 μg per dose) or were sham immunized with AAHSA alone. The doses were administered as two 50-μl intramuscular injections on days 0, 7, and 21(Kuklin et al., 2006).
  • Challenge Protocol: 35 days after vaccination, mice were challenged with an 80 to 90% lethal dose (LD80-90) of S. aureus Becker (4.9 × 108 to 8.7 × 108 CFU for BALB/c mice and 1.0 × 109 to 2.0 × 109 CFU for ICR mice), and survival was monitored for 10 days. (Kuklin et al., 2006).
  • Efficacy: Mice immunized with IsdB exhibited greater survival (45, 40, 32, 29, 40, and 40%) than the mice in the sham-immunized control group (Kuklin et al., 2006).

Mouse Response

  • Persistence: An aroA mutant is attenuated in mice (Buzzola et al., 2006).
  • Efficacy: An aroA mutant induces significant protection in mice from challenge with wild type S. aureus (Buzzola et al., 2006).
  • Host Ifng (Interferon gamma) response
    • Description: Ninety-six hours after challenge with the wild-type strain RN6390 or heterologous strain MB319, the relative mRNA levels of IFN-γ and IL-4 were determined in mammary glands by RT-PCR. Mammary glands from mice immunized with the aroA mutant showed a significant increase in the level of IFN-γ transcripts compared with control, unvaccinated mice (Buzzola et al., 2006).
    • Detailed Gene Information: Click Here.
  • Host Il4 (interleukin 4) response
    • Description: Ninety-six hours after challenge with the wild-type strain RN6390 or heterologous strain MB319, the relative mRNA levels of IFN-γ and IL-4 were determined in mammary glands by RT-PCR. Mice immunized with the aroA mutant showed a significant increase in the level of IL-4 transcripts compared with control, unvaccinated mice (Buzzola et al., 2006).
    • Detailed Gene Information: Click Here.
References References References References References References References References
Josefsson et al., 2001: Josefsson E, Hartford O, O'Brien L, Patti JM, Foster T. Protection against experimental Staphylococcus aureus arthritis by vaccination with clumping factor A, a novel virulence determinant. The Journal of infectious diseases. 2001; 184(12); 1572-1580. [PubMed: 11740733].
Nilsson et al., 1998: Nilsson IM, Patti JM, Bremell T, Höök M, Tarkowski A. Vaccination with a recombinant fragment of collagen adhesin provides protection against Staphylococcus aureus-mediated septic death. The Journal of clinical investigation. 1998; 101(12); 2640-2649. [PubMed: 9637697].
Castagliuolo et al., 2006: Castagliuolo I, Piccinini R, Beggiao E, Palù G, Mengoli C, Ditadi F, Vicenzoni G, Zecconi A. Mucosal genetic immunization against four adhesins protects against Staphylococcus aureus-induced mastitis in mice. Vaccine. 2006; 24(20); 4393-4402. [PubMed: 16580097].
Senna et al., 2003: Senna JP, Roth DM, Oliveira JS, Machado DC, Santos DS. Protective immune response against methicillin resistant Staphylococcus aureus in a murine model using a DNA vaccine approach. Vaccine. 2003; 21(19-20); 2661-2666. [PubMed: 12744903].
Gaudreau et al., 2007: Gaudreau MC, Lacasse P, Talbot BG. Protective immune responses to a multi-gene DNA vaccine against Staphylococcus aureus. Vaccine. 2007; 25(5); 814-824. [PubMed: 17027124].
Mamo et al., 1994: Mamo W, Jonsson P, Flock JI, Lindberg M, Müller HP, Wadström T, Nelson L. Vaccination against Staphylococcus aureus mastitis: immunological response of mice vaccinated with fibronectin-binding protein (FnBP-A) to challenge with S. aureus. Vaccine. 1994; 12(11); 988-992. [PubMed: 7975852].
Kuklin et al., 2006: Kuklin NA, Clark DJ, Secore S, Cook J, Cope LD, McNeely T, Noble L, Brown MJ, Zorman JK, Wang XM, Pancari G, Fan H, Isett K, Burgess B, Bryan J, Brownlow M, George H, Meinz M, Liddell ME, Kelly R, Schultz L, Montgomery D, Onishi J, Losada M, Martin M, Ebert T, Tan CY, Schofield TL, Nagy E, Meineke A, Joyce JG, Kurtz MB, Caulfield MJ, Jansen KU, McClements W, Anderson AS. A novel Staphylococcus aureus vaccine: iron surface determinant B induces rapid antibody responses in rhesus macaques and specific increased survival in a murine S. aureus sepsis model. Infection and immunity. 2006; 74(4); 2215-2223. [PubMed: 16552052].
Buzzola et al., 2006: Buzzola FR, Barbagelata MS, Caccuri RL, Sordelli DO. Attenuation and persistence of and ability to induce protective immunity to a Staphylococcus aureus aroA mutant in mice. Infection and immunity. 2006; 74(6); 3498-3506. [PubMed: 16714581].