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Vaccine Comparison

DNA vaccine expressing PspA pneumococcal polysaccharide conjugate vaccine serotype 1 (PNC-1) PsaA DNA Vaccine S. pneumoniae 6PGD Protein Vaccine S. pneumoniae CbpA Protein Vaccine S. pneumoniae ClpP protein Vaccine S. pneumoniae GtS Protein Vaccine S. pneumoniae PhpA-79 Protein Vaccine S. pneumoniae PiaA Protein Vaccine S. pneumoniae PspA Protein Vaccine S. pneumoniae pspA-rBCG Vector Vaccine S. pneumoniae RASV synthesizing PsaA S. pneumoniae SrtA Protein Vaccine
Vaccine Information Vaccine Information 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_0004516
  • Type: DNA vaccine
  • Status: Research
  • PspA gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Vector: pSecTag2A (Ferreira et al., 2006)
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004265
  • Type: Conjugate vaccine
  • Status: Research
  • Adjuvant: LTK72 vaccine adjuvant
  • Immunization Route: intranasal immunization
  • Vaccine Ontology ID: VO_0004517
  • Type: DNA vaccine
  • Status: Licensed
  • psaA gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Vector: pCI (Miyaji et al., 2001)
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004069
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Recombinant 6-Phosphogluconate dehydrogenase (6PGD) (Daniely et al., 2006).
  • Gnd gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: aluminum vaccine adjuvant
    • VO ID: VO_0000884
    • Description: Inject Alum adjuvant (Daniely et al., 2006).
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Vaccine Ontology ID: VO_0004005
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: N-terminal fragment of choline binding protein A (CbpA) (Ogunniyi et al., 2001).
  • CbpA gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: MPL vaccine adjuvant
    • VO ID: VO_0001250
    • Description: Monophospholipid A (MPL) and aluminium phosphate (AlPO4) (Ogunniyi et al., 2001).
  • Adjuvant: aluminum phosphate vaccine adjuvant
    • VO ID: VO_0000128
    • Description: Monophospholipid A (MPL) and aluminium phosphate (AlPO4) (Ogunniyi et al., 2001).
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Vaccine Ontology ID: VO_0004006
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: ATP-dependent caseinolytic protease (ClpP)
  • ClpP gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: aluminum hydroxide vaccine adjuvant
    • VO ID: VO_0000127
    • Description: Imject Alum no. 77161
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Vaccine Ontology ID: VO_0004068
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: recombinant (r) Glutamyl tRNA synthetase (GtS) (Mizrachi et al., 2007).
  • GltX gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: aluminum vaccine adjuvant
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Vaccine Ontology ID: VO_0004063
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Recombinant PhpA-79
  • phpA gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: MPL vaccine adjuvant
  • Immunization Route: subcutaneous injection
  • Vaccine Ontology ID: VO_0004070
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Recombinant PiaA protein (Brown et al., 2001).
  • PiaA gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: aluminum vaccine adjuvant
    • VO ID: VO_0000884
    • Description: Imject Alum No. 77161
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Vaccine Ontology ID: VO_0004007
  • Type: Subunit vaccine
  • Status: Research
  • PspA gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: aluminum vaccine adjuvant
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Vaccine Ontology ID: VO_0004601
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • Antigen: Pneumococcal surface protein A (PspA) present on all strains of pneumococci (Langermann et al., 1994)
  • PspA gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Vector: recombinant Bacille Calmette-Guerin (rBCG) (Langermann et al., 1994)
  • Immunization Route: Intramuscular injection (i.m.)
  • Description: Streptococcus pneumoniae is one of the leading causes of bacterial pneumonia and acute otitis media, a type of meningitis. It is becoming increasingly antibiotic resistant and the current available vaccine does not elicit protection in children. (Langermann et al., 1994)
  • Vaccine Ontology ID: VO_0004071
  • Type: Recombinant vector vaccine
  • Status: Research
  • psaA gene engineering:
    • Type: Recombinant vector construction
    • Detailed Gene Information: Click Here.
  • Vector: Attenuated Salmonella enterica serovar Typhimurium strain RASV (Wang et al., 2010).
  • Immunization Route: Intranasally
  • Vaccine Ontology ID: VO_0004008
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Recombinant sortase A (SrtA) (Gianfaldoni et al., 2009).
  • SrtA gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: Freunds emulsified oil adjuvant
  • Immunization Route: Intraperitoneal injection (i.p.)
Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response

Mouse Response

  • Vaccination Protocol: Groups of at least six mice were inoculated intramuscularly with 50 μl of 10 μM cardiotoxin into each tibialis anterior muscle, 5 days before immunization with 50 μg vaccine vector in PBS (100 μl). Mice received a booster after 3 weeks with the same dose of plasmid DNA. For immunization with recombinant protein, mice were injected subcutaneously with 5 μg rPspA3NS, using aluminium hydroxide as the adjuvant, and also boosted 3 weeks after priming (Ferreira et al., 2006).
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: Animals immunized with a vector expressing secreted PspA developed higher levels of antibody than mice immunized with the vector expressing the antigen in the cytosol (Ferreira et al., 2006).
  • Challenge Protocol: Immunized mice were challenged by intraperitoneal injection of 200 c.f.u. S. pneumoniae strain St 679/99 (PspA clade 3, serotype 6B) in 0·5 ml saline 6 weeks after priming. Animals were then observed for 2 weeks (Ferreira et al., 2006).
  • Efficacy: All the immunized groups showed significant protection when compared with control groups. Animals immunized with pSec-pspA3NS showed a tendency towards increased survival when compared with animals primed with rPspA3NS (Ferreira et al., 2006).

Mouse Response

  • Host Strain: NMRI
  • Vaccination Protocol: Mice were immunized i.n. with 0.5 or 2.0 μg of PNC-1 alone or mixed with either LT-K63 or LT-R72 (Jakobsen et al., 1999).
  • Immune Response: Administration of PNC-1 i.n. with either LT-K63 or LT-R72 elicited significantly higher antibody responses than the s.c. route for both 0.5- and 2.0-μg doses of PNC-1 in saline (Jakobsen et al., 1999).
  • Challenge Protocol: Mice were challenged with 50 μl of pneumococcal suspension i.n. and were allowed to aspirate it into the lungs for 10 min (Jakobsen et al., 1999).
  • Efficacy: Immunization i.n. with PNC-1 and LT-K63 or LT-R72 conferred 100% clearance of lung infection caused by serotype 1 pneumococci (Jakobsen et al., 1999).

Mouse Response

  • Vaccination Protocol: Five male BALB/c mice were inoculated into each muscle tibialis anterior as previously described with 100 μl of 10 μM cardiotoxin and after 5 days with 25 μg of plasmid DNA in PBS (50 μl) (Miyaji et al., 2001).
  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: Analysis of sera from mice immunized with purified PsaA showed the induction of mostly IgG1, that is, a Th2 like response. Furthermore, mice immunized with pCI-psaA developed readily detectable serum antibody titers 1 month after priming (Miyaji et al., 2001).
  • Efficacy: Immunization of mice with purified PsaA was shown to be protective against challenge with an heterologous S. pneumoniae strain (Miyaji et al., 2001).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Six-week-old BALB/c female mice were immunized intraperitoneally with 25 µg of r6PGD and 75 µl of Inject Alum adjuvant on days 0 (primary immunization) and 21 (booster). Control mice were sham-immunized with adjuvant only (Daniely et al., 2006).
  • Challenge Protocol: For respiratory challenge r6PGD immunized and control mice were anaesthetized with pentobarbital sodium (0·6 mg/kg) and inoculated intranasally with 1 × 108 S. pneumoniae strain WU2 (in 25 µl PBS). This inoculum's size was used as it was found to be the lowest that causes 100% mortality in our mouse model system within 96 h. Survival was monitored daily (Daniely et al., 2006).
  • Efficacy: Immunization of mice with r6PGD protected 60% (P < 0.001) of mice for 5 days and 40% (P < 0.05) of the mice for 21 days following intranasal lethal challenge (Daniely et al., 2006).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: 5- to 6-week-old male BALB/c mice (13 to 15 per group) were immunized intraperitoneally with either adjuvant alone, adjuvant plus CbpA, or CbpA alone. Each mouse received three doses of 10 μg of each protein antigen in either formulation (AlPO4 or MPL plus AlPO4) at 12- to 14-day intervals (Ogunniyi et al., 2001).
  • Challenge Protocol: Intraperitoneal-challenge experiments were carried out 2 weeks after the third immunization using a highly virulent capsular type 2 strain (D39). Groups of immunized BALB/c mice were infected with either 1.3 × 105 or 1.3 × 107 CFU of the challenge strain. The challenge dose was equivalent to approximately 103 or 105 times the 50% lethal dose (LD50), respectively, for BALB/c mice. The mice were closely monitored for 21 days, and the survival time of each mouse was recorded (Ogunniyi et al., 2001).
  • Efficacy: CbpA was able to protect mice from intraperitoneal challenge with medium to very high doses of a highly virulent capsular type 2 pneumococcal strain, D39 (Ogunniyi et al., 2001).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Female BALB/c mice, weighing 16 to 18 g, were immunized three times at 14-day intervals with 10 µg of protein in alum adjuvant (3:1 [vol/vol]) of either ClpP protein in alum adjuvant or control protein in alum. Mice were boosted intraperitoneally with the same doses on days 14 and 28 (Wu et al., 2010).
  • Challenge Protocol: For the intraperitoneal challenge models, at 2 weeks after the last immunization BALB/c mice were administrated the virulent pneumococcal strain D39 at 1,500 times the 50% lethal dose (LD50; 1.5 x 105 CFU) or 150 times the LD50 (2.0 x 104 CFU). In the focal pneumonia models, BALB/c mice were intranasally inoculated with pneumococcal strain 31614 (serotype 14, 1.5 x 106 CFU) or 31693 (serotype 19F, 107 CFU). For intranasal challenge with pneumococcal strain D39, mice inspired the virulent pneumococcal strain D39 at 104 (7.5 x 107 CFU) or 103 (6.0 x 106 CFU) times the LD50 in a volume of 40 µl under injection anesthesia (Wu et al., 2010).
  • Efficacy: Compared to the control protein, ClpP reduced the median bacterial load nearly 100-fold in the focal pneumonia model (Wu et al., 2010).

Mouse Response

  • Host Strain: BALB/c OlaHsd
  • Vaccination Protocol: Mice were immunized intraperitoneally with 25 μg of rGtS and 75 μL of Imject Alum adjuvant on days 0 and 21. Control mice were sham immunized with adjuvant only (Mizrachi et al., 2007).
  • Challenge Protocol: For lethal respiratory challenge with S. pneumoniae, rGtS‐immunized and control mice were anesthetized with isoflurane and inoculated intranasally with S. pneumoniae serotype 3 strain WU2 (in 25 μL of PBS). The size of this inoculum was found to be the lowest that causes 100% mortality in control mice within 96 h. Survival was monitored daily (Mizrachi et al., 2007).
  • Efficacy: Thirty-nine percent of rGtS-immunized mice survived a lethal bacterial challenge, whereas no control mice survived (Mizrachi et al., 2007).

Mouse Response

  • Host Strain: CBA/N
  • Vaccination Protocol: CBA/N mice, at 10 animals per group, were immunized with 5 μg of either rPhpA-79 or rPhpA-20. For parenteral immunization, rPhpA-79 or rPhpA-20 protein was mixed with 100 μg of monophosphoryl lipid A (MPL; Corixa, Hamilton, Mont.) per dose to a final volume of 200 μl in saline and then injected s.c. into mice. All groups received a booster with the same dose and by the same route 3 and 5 weeks after the primary immunization. Control mice were injected with MPL alone (Zhang et al., 2001).
  • Challenge Protocol: Mice were challenged with either serotype 3 or serotype 14 streptomycin-resistant S. pneumoniae (Zhang et al., 2001).
  • Efficacy: Immunization with either rPhpA-79–MPL provided 100% protection against death caused by type 3 S. pneumoniae infection (Zhang et al., 2001).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: For the active protection experiments, each mouse was immunized by intraperitoneal (i.p.) injection of 100 μl of each protein preparation in alum adjuvant on days 0, 10, and 20 (Brown et al., 2001).
  • Challenge Protocol: On day 34 mice were challenged i.p. with ca. 106 CFU of S. pneumoniae strain D39 organisms (Brown et al., 2001).
  • Efficacy: After 14 days the mortality of the group of mice immunized PiuA was 52%, showing that immunization with these proteins protects against systemic infection with S. pneumoniae (Brown et al., 2001).

Mouse Response

  • Host Strain: BALB/c and CD1
  • Vaccination Protocol: The mice received three doses of 10 μg of each antigen alone (or in combination) in 100 μg of alum adjuvant via Intraperitoneal injection (i.p.) at 14-day intervals or a placebo (Ogunniyi et al., 2007).
  • Challenge Protocol: Mice were challenged i.p. 2 weeks after the third immunization with either the highly virulent capsular type 2 strain D39 or a serotype 6A (WCH16) strain (Ogunniyi et al., 2007).
  • Efficacy: PspA elicited protection by using moderate challenge doses of S. pneumoniae (Ogunniyi et al., 2007).

Mouse Response

  • Host Strain: BALB/c and C3H/HeJ mice
  • Vaccination Protocol: A single intraperitoneal inoculation with a live BCG bacterial vaccine expressing PspA as a secreted mature protein in or a chimeric exported lipoprotein (rBCG-PspA), followed by a booster at 17 weeks(Langermann et al., 1994)
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: BALB/c and C3H/HeJ mice immunized with rBCG-PspA vaccine strains were challenged intraperitoneally with 104 CFU of the highly lethal S. pneumoniae strain WU2 (Langermann et al., 1994)
  • Challenge Detail:
    No. Pathogen Name Dose Route Age Interval
    1 S. pneumoniae strain WU2 10000 CFU in volume ml Intraperitoneal injection (i.p.) day day
  • Efficacy: Mice experienced passive protection with the use of rBCG against lethal challenge with the highly virulent, encapsulated WU2 strain of Streptococcus pneumoniae and two additional virulent strains exhibiting heterologous PspA and capsular sero- types(Langermann et al., 1994)

Mouse Response

  • Host Strain: BALB/c, C57BL/6J
  • Vaccination Protocol: Mice were inoculated intranasally with 10 µl or orally with 20 µl of BSG containing 1 x 109 CFU of the RASV or control strain. In some experiments, the mice were boosted at week 6 with the same dose by using the same route as that used for primary immunization (Wang et al., 2010).
  • Challenge Protocol: At week 10, mice were challenged either by intraperitoneal injection with 2 x 104 CFU of S. pneumoniae WU2 (equal to 100x the 50% lethal dose [LD50]) or intranasally with 20 µl containing 5 x 106 CFU S. pneumoniae strain L82016 or E134 or 1 x 107 CFU of strain A66.1 or D39 (Wang et al., 2010).
  • Efficacy: BALB/c (haplotype H2(d)) or C57BL/6 (haplotype H2(b)) mice vaccinated either orally or intranasally exhibited a significant reduction in colonization of nasopharyngeal tissues after intranasal challenge with S. pneumoniae strains compared to controls, although protection was not observed with all challenge strains (Wang et al., 2010).

Mouse Response

  • Host Strain: BALB/c mice
  • Vaccination Protocol: Specific-pathogen-free BALB/c mice (Charles River) received three intraperitoneal administrations, 2 weeks apart, of 20 μg of SrtA along with Freund's adjuvant. Controls received the same course of saline plus adjuvant (Gianfaldoni et al., 2009).
  • Challenge Protocol: Three weeks after the last immunization, the animals were challenged intraperitoneally with one of the following S. pneumoniae strains: TIGR4, 1.4 × 102 CFU/mouse; D39, 103 CFU/mouse; or 35B-SME15, 7 × 103 CFU/mouse (Gianfaldoni et al., 2009).
  • Efficacy: Intraperitoneal immunization with recombinant SrtA was found to have conferred to mice protection against S. pneumoniae intraperitoneal challenge and the passive transfer of immune serum before intraperitoneal challenge was also protective. Moreover, by using the intranasal challenge model, significant reduction of bacteremia when mice were intraperitoneally immunized with SrtA was observed, while a moderate decrease of lung infection was achieved by intranasal immunization, even though no influence on nasopharynx colonization was seen (Gianfaldoni et al., 2009).
References References References References References References References References References References References References References
Ferreira et al., 2006: Ferreira DM, Miyaji EN, Oliveira ML, Darrieux M, Arêas AP, Ho PL, Leite LC. DNA vaccines expressing pneumococcal surface protein A (PspA) elicit protection levels comparable to recombinant protein. Journal of medical microbiology. 2006; 55(Pt 4); 375-378. [PubMed: 16533983].
Jakobsen et al., 1999: Jakobsen H, Schulz D, Pizza M, Rappuoli R, Jónsdóttir I. Intranasal immunization with pneumococcal polysaccharide conjugate vaccines with nontoxic mutants of Escherichia coli heat-labile enterotoxins as adjuvants protects mice against invasive pneumococcal infections. Infection and immunity. 1999; 67(11); 5892-5897. [PubMed: 10531245].
Miyaji et al., 2001: Miyaji EN, Dias WO, Gamberini M, Gebara VC, Schenkman RP, Wild J, Riedl P, Reimann J, Schirmbeck R, Leite LC. PsaA (pneumococcal surface adhesin A) and PspA (pneumococcal surface protein A) DNA vaccines induce humoral and cellular immune responses against Streptococcus pneumoniae. Vaccine. 2001; 20(5-6); 805-812. [PubMed: 11738744].
Daniely et al., 2006: Daniely D, Portnoi M, Shagan M, Porgador A, Givon-Lavi N, Ling E, Dagan R, Mizrachi Nebenzahl Y. Pneumococcal 6-phosphogluconate-dehydrogenase, a putative adhesin, induces protective immune response in mice. Clinical and experimental immunology. 2006; 144(2); 254-263. [PubMed: 16634799].
Ogunniyi et al., 2001: Ogunniyi AD, Woodrow MC, Poolman JT, Paton JC. Protection against Streptococcus pneumoniae elicited by immunization with pneumolysin and CbpA. Infection and immunity. 2001; 69(10); 5997-6003. [PubMed: 11553536].
Wu et al., 2010: Wu K, Zhang X, Shi J, Li N, Li D, Luo M, Cao J, Yin N, Wang H, Xu W, He Y, Yin Y. Immunization with a combination of three pneumococcal proteins confers additive and broad protection against Streptococcus pneumoniae Infections in Mice. Infection and immunity. 2010; 78(3); 1276-1283. [PubMed: 20038538].
Mizrachi et al., 2007: Mizrachi Nebenzahl Y, Bernstein A, Portnoi M, Shagan M, Rom S, Porgador A, Dagan R. Streptococcus pneumoniae surface-exposed glutamyl tRNA synthetase, a putative adhesin, is able to induce a partially protective immune response in mice. The Journal of infectious diseases. 2007; 196(6); 945-953. [PubMed: 17703427].
Zhang et al., 2001: Zhang Y, Masi AW, Barniak V, Mountzouros K, Hostetter MK, Green BA. Recombinant PhpA protein, a unique histidine motif-containing protein from Streptococcus pneumoniae, protects mice against intranasal pneumococcal challenge. Infection and immunity. 2001; 69(6); 3827-3836. [PubMed: 11349048].
Brown et al., 2001: Brown JS, Ogunniyi AD, Woodrow MC, Holden DW, Paton JC. Immunization with components of two iron uptake ABC transporters protects mice against systemic Streptococcus pneumoniae infection. Infection and immunity. 2001; 69(11); 6702-6706. [PubMed: 11598041].
Ogunniyi et al., 2007: Ogunniyi AD, Grabowicz M, Briles DE, Cook J, Paton JC. Development of a vaccine against invasive pneumococcal disease based on combinations of virulence proteins of Streptococcus pneumoniae. Infection and immunity. 2007; 75(1); 350-357. [PubMed: 17088353].
Langermann et al., 1994: Langermann S, Palaszynski SR, Burlein JE, Koenig S, Hanson MS, Briles DE, Stover CK. Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guérin vaccines expressing pneumococcal surface protein A. The Journal of experimental medicine. 1994; 180(6); 2277-2286. [PubMed: 7964500].
Wang et al., 2010: Wang S, Li Y, Shi H, Scarpellini G, Torres-Escobar A, Roland KL, Curtiss R 3rd. Immune responses to recombinant pneumococcal PsaA antigen delivered by a live attenuated Salmonella vaccine. Infection and immunity. 2010; 78(7); 3258-3271. [PubMed: 20479086].
Gianfaldoni et al., 2009: Gianfaldoni C, Maccari S, Pancotto L, Rossi G, Hilleringmann M, Pansegrau W, Sinisi A, Moschioni M, Masignani V, Rappuoli R, Del Giudice G, Ruggiero P. Sortase A confers protection against Streptococcus pneumoniae in mice. Infection and immunity. 2009; 77(7); 2957-2961. [PubMed: 19433540].