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Vaccine Comparison

Ag85B and ESAT-6 fusion protein
Vaccine Information
  • Vaccine Name: Ag85B and ESAT-6 fusion protein
  • Vaccine Ontology ID: VO_0000536
  • Type: Conjugate vaccine
  • Antigen: Two immunodominant antigens, Ag85B and ESAT-6, were used in the analysis. ESAT-6 is a 6-kDA early secretory antigenic target. The two antigens are combined as a fusion protein in the vaccine (Olsen et al., 2001).
  • EsxA (ESAT-6) gene engineering:
    • Type: Fusion protein ESAT6-Ag85B
    • Description: Fusion protein created in E. coli using His-tag cloning system pMCT6. Proteins were affinity purified, separated via ion exchange chromatography, and analyzed with SDS-PAGE and Western blots (Olsen et al., 2001).
    • Detailed Gene Information: Click Here.
  • Ag85B from M. tuberculosis H37Rv gene engineering:
    • Type: Fusion protein Ag85B-ESAT6
    • Detailed Gene Information: Click Here.
  • Adjuvant:
    • VO ID: VO_0001250
    • Description: 1 25 μg amount of monoposphoryl lipid A (MPL) adjuvant was added to 250μg dimethyl dioctadecylammonium bromide (DDA) emulsifier per 0.01-50μg of vaccine.
  • Adjuvant:
  • Preparation: M tuberculosis Erdamn and H37Rv were grown in media, while BCG Danish 1331 was acquired as a freeze dried-vaccine and replenished (Olsen et al., 2001). Recombinant ESAT-6 was obtained along with short-term culture filtrate. Esat6 and ag85B coding regions were obtained by PCR amplification from M. tuberculosis H37Rv chromosomal DNA using selected primers. PCR products were digested by two restriction endonucleases and cloned into pMCT6 prior to sequencing. The E. coli XL-1 Blue was used to express the His-tagged protein prior to purification, protein anion-exchange chromatography, and dialysis. PCR fragments per gene were joined at a HindIII site, cloned into pMCT6, expressed, and later purified to create a fusion protein and a chimeric plasmid.

References
Olsen et al., 2001: Olsen, A.W., L.A.H. van Pinxteren, P.B Rasmussen, and P. Andersen. Protection of Mice with a Tuberculosis Subunit Vaccine Based on a Fusion Protein of Antigen 85B and ESAT-6. Infect. Immun.. 2001; 69(5); 2773-2778.
Arabinomannan-tetanus toxoid conjugate
Vaccine Information
  • Vaccine Name: Arabinomannan-tetanus toxoid conjugate
  • Vaccine Ontology ID: VO_0000528
  • Type: Conjugate vaccine
  • Antigen: Arabinomannan (AM) oligosaccharides. They are derived from Lipoarabinomannan (LAM), a carbohydrate antigen expressed on the surface of mycobacteria which contains a manna polysaccharide core attached to a phosphatidyl inositol lipid moiety (Hamasur et al., 2003). The surface carbohydrate was hypothesized to yield CD1-specific immune responses, promote mycobacterial clearance, downregulate T cell proliferation, and interfere with activation of macrophages through interferon gamma intervention (Hamasur et al., 2003).
  • Ag85B from M. tuberculosis H37Rv gene engineering:
    • Type: Conjugate protein purified from LAM
    • Description: The 28-kDa AM oligos were pooled and linked to tetanus toxoid (TT) or other M. tuberculosis proteins (Ag85B, 75-kDa protein) with thioether linkage generated by conjugation method. Conjugation consisted of amination of AMO with ammonium chloride and sodium cyanoborohydride, deasalting and treatment with 2-imminothiolane, and end conjugation between thiolated oligsaccharide derivatives with bromoacetylated proteins and tributyl phosphine (Hamasur et al., 2003).
    • Detailed Gene Information: Click Here.
  • Adjuvant:
    • VO ID: VO_0000127
    • Description: Alum (aluminum hydroxide gel) adjuvant was used initially. Eurocine L3 suspension adjuvant was prepared using 1:1 ratio solid monooleate and oleic acid, Tris buffer with pH adjustment including NaOH, and subsequent sonification. Eurocine L3 emulsion was prepared using 1:1 ratio solid monooleate and oleic acid which were liquified prior to addition of soy bean oil (Hamasur et al., 2003).
  • Preparation: Arabinomannan (AM) oligosaccharides derived from LAM of Mycobacterium tuberculosis H37Rv were isolated and covalently conjugated to tetanus toxoid (TT) or to short-term culture filtrate proteins (antigen 85B (Ag85B) or a 75kDa protein) from M. tuberculosis strain Harlingen (Hamasur et al., 2003).
References
Hamasur et al., 2003: Hamasur B, Haile M, Pawlowski A, Schroder U, Williams A, Hatch G, Hall G, Marsh P, Kallenius G, Svenson SB. Mycobacterium tuberculosis arabinomannan-protein conjugates protect against tuberculosis. Vaccine. 2003 Sep 8; 21(25-26); 4081-93. [PubMed: 12922145].
DAAV using PA and PGA
Vaccine Information
  • Vaccine Name: DAAV using PA and PGA
  • Vaccine Ontology ID: VO_0000522
  • Type: Conjugate vaccine
  • Antigen: Two antigens: PA-B and capsular poly-γ-d-glutamate. Both antigens are conjugated.
  • PagA from B. anthracis str. 'Ames Ancestor' gene engineering:
    • Type: Protein
    • Detailed Gene Information: Click Here.
  • Adjuvant:
    • VO ID: VO_0001241
    • Description: Anthrax involves a dual process of bacterial replication and toxin production. The dually active anthrax vaccine (DAAV) confers simultaneous protection against both bacilli and toxins was highly sought after through research. The weakly immunogenic and antiphagocytic PGA capsule disguises the bacilli from immune surveillance in a similar manner to the role of capsular polysaccharides in protecting pathogens, such as pneumococci and meningococci. Encapsulated B. anthracis strains grow unimpeded in the infected host, whereas isolates lacking the capsule are phagocytized and are virtually avirulent. Anthrax toxins are formed by PA, lethal factor (LF), and edema factor (EF), which are secreted separately as nontoxic monomers. The binding of LF or EF to PA results in the formation of active lethal toxin (LT) or edema toxin (ET), respectively. Because of its ability to elicit a protective immune response against both anthrax toxins, PA is the target antigen of existing anthrax vaccine. However, a vaccine based on both PGA and PA might allow direct targeting of bacillar growth, as well as inhibiting toxin activity, making it more effective than a vaccine based on PA alone. PGA is an attractive antigen because it consists of d-glutamic acid residues linked by γ peptide bonds, and thus bears no resemblance to mammalian host molecules (Rhie et al., 2003).
  • Preparation: This conjugate vaccine is constructed by conjugating two major virulence factors of B. anthracis, the capsular poly-γ-D-glutamic acid (PGA) and the essential toxin component and protective antigen (PA). This is a DAAV that confers simultaneous protection against both bacilli and toxins. Two sets of conjugates with 1:2 and 1:1 (wt/wt) PGA-to-PA ratios, designated DAAV-1 and DAAV-2, respectively (Rhie et al., 2003).
  • Virulence: (Rhie et al., 2003)
  • Description: Anthrax involves a dual process of bacterial replication and toxin production. The dually active anthrax vaccine (DAAV) confers simultaneous protection against both bacilli and toxins was highly sought after through research. The weakly immunogenic and antiphagocytic PGA capsule disguises the bacilli from immune surveillance in a similar manner to the role of capsular polysaccharides in protecting pathogens, such as pneumococci and meningococci. Encapsulated B. anthracis strains grow unimpeded in the infected host, whereas isolates lacking the capsule are phagocytized and are virtually avirulent. Anthrax toxins are formed by PA, lethal factor (LF), and edema factor (EF), which are secreted separately as nontoxic monomers. The binding of LF or EF to PA results in the formation of active lethal toxin (LT) or edema toxin (ET), respectively. Because of its ability to elicit a protective immune response against both anthrax toxins, PA is the target antigen of existing anthrax vaccine. However, a vaccine based on both PGA and PA might allow direct targeting of bacillar growth, as well as inhibiting toxin activity, making it more effective than a vaccine based on PA alone. PGA is an attractive antigen because it consists of d-glutamic acid residues linked by γ peptide bonds, and thus bears no resemblance to mammalian host molecules (Rhie et al., 2003).
References
Rhie et al., 2003: Rhie GE, Roehrl MH, Mourez M, Collier RJ, Mekalanos JJ, Wang JY. A dually active anthrax vaccine that confers protection against both bacilli and toxins. Proceedings of the National Academy of Sciences of the United States of America. 2003 Sep 16; 100(19); 10925-30. [PubMed: 12960361].
pneumococcal polysaccharide conjugate vaccine serotype 1 (PNC-1)
Vaccine Information
References
 
Prevnar 13
Vaccine Information
  • Vaccine Name: Prevnar 13
  • Product Name: Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]
  • Tradename: Prevnar
  • Manufacturer: Wyeth Pharmaceuticals, Inc
  • Vaccine Ontology ID: VO_0001244
  • CDC CVX code: 133
  • Type: Conjugate vaccine
  • Status: Licensed
  • Location Licensed: USA, Canada
  • Host Species for Licensed Use: Human
  • Adjuvant:
  • Immunization Route: Intramuscular injection (i.m.)
  • Storage: Store refrigerated at +2ºC to +8ºC (36ºF to 46ºF)
  • Approved Age for Licensed Use: Children 6 weeks through 5 years of age (FDA: Prevnar 13).
References
FDA: Prevnar 13: FDA: Prevnar 13 [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm201667.htm]
Synflorix
Vaccine Information
  • Vaccine Name: Synflorix
  • Product Name: Pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed
  • Tradename: Synflorix
  • Manufacturer: GlaxoSmithKline Inc.
  • Vaccine Ontology ID: VO_0001245
  • Type: Conjugate vaccine
  • Status: Licensed
  • Location Licensed: Canada
  • Host Species for Licensed Use: Human
  • Antigen: Pneumococcal polysaccharides of serotypes 1,4,5,6B,7F,9V,14,18C,19F,23F (GSK: Synflorix).
  • Adjuvant:
  • Immunization Route: Intramuscular injection (i.m.)
  • Storage: Store in a refrigerator (2°C - 8°C).
  • Approved Age for Licensed Use: Infants and children from 6 weeks up to 2 years of age (GSK: Synflorix).
  • Description: SYNFLORIX™ [(pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed] is a 10- valent pneumococcal polysaccharide conjugate vaccine using protein D derived from Non-Typeable Haemophilus influenzae as a carrier protein for 8 out of the 10 serotypes (1, 4, 5, 6B, 7F, 9V, 14 and 23F). Serotypes 18C and 19F are conjugated to tetanus toxoid and to diphtheria toxoid, respectively. All conjugates are adsorbed onto aluminum phosphate (GSK: Synflorix).
References
GSK: Synflorix: GSK: Synflorix [http://www.gsk.ca/english/docs-pdf/Synflorix_PM_20090505_EN.pdf]