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Vaccine Detail

DAAV using PA and PGA
Vaccine Information
  • Vaccine Name: DAAV using PA and PGA
  • Target Pathogen: Bacillus anthracis
  • Target Disease: Anthrax
  • 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
    • Description:
    • Detailed Gene Information: Click Here.
  • Adjuvant: Alhydrogel
    • Adjuvant name: Alhydrogel
    • VO adjuvant 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).
Host Response

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Groups of female BALB/c mice at 6–8 weeks of age were immunized by i.p. injection on days 0, 14, and 28. DAAV-1 was tested at 10- and 20-µg doses, and DAAV-2 was tested at 2-, 10-, and 20-µg doses (doses refer to PA content). Controls include PA and PGA at 20-µg doses, unconjugated PGA–PA mixture including 20 µg of PGA and 20 µg of PA. Each dose was dissolved in 50 µl of PBS and adsorbed to an equal volume of Al(OH)3 gel adjuvant (equivalent to 0.187 mg per dose). PBS/Al(OH)3 was used as a negative control (Rhie et al., 2003).
  • Persistence: (Rhie et al., 2003)
  • Side Effects: None were noted (Rhie et al., 2003).
  • Efficacy: After three immunizations in mice, DAAV-1 induced high levels of serum anti-PGA IgG, and booster injections significantly enhanced the IgG response. PGA-specific antibodies bound to encapsulated bacilli and promoted the killing of bacilli by complement. PA-specific antibodies neutralized toxin activity and protected immunized mice against lethal challenge with anthrax toxin. Thus, DAAV combines both antibacterial and antitoxic components in a single vaccine against anthrax (Rhie et al., 2003).
  • Description: PGA-specific antibodies bound to encapsulated bacilli and promoted the killing of bacilli by complement. PA-specific antibodies neutralized toxin activity and protected immunized mice against lethal challenge with anthrax toxin. Thus, DAAV combines both antibacterial and antitoxic components in a single vaccine against anthrax. DAAV introduces a vaccine design that may be widely applicable against infectious diseases and provides additional tools in medicine and biodefense (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].