Abzyme basic science

  • Discovery of naturally occurring catalytic antibodies (abzymes) by Paul et al in 1989 (1)
  • Independent reproduction of naturally occurring abzymes by several groups (2-14)
  • Identification by Paul group of abzyme covalent catalytic mechanism as an example of convergent evolution with classical serine protease family of enzymes (15)
  • Independent reproduction of serine protease-like catalysis by antibodies by several groups (16- 21)

Amyloid ß targeting by abzymes

  • Discovery of cross-reactive amyloid ß-degrading abzymes by Sierks group (22) using catalytic antibody light chain subunits supplied by Paul group
  • Discovery of abzyme clearance of amlyoid ß as a physiological mechanism in old age and Alzheimer’s patients by Paul group (23)
  • Engineering of efficient amyloid ß degrading abzymes by Paul group (24)
  • Independent demonstration of amyloid plaque removal from transgenic mouse brain by foregoing abzymes by Sigurdsson group (to be published)
  • Task ahead: Establishing safety and efficacy of amyloid β degrading abzymes for treatment of Alzheimer’s disease in animals and humans

Identifying the Achilles heel of HIV

  • Discovery of antibodies from non-infected humans that bind 421-433 region of HIV gp120 weakly by Braun group (25) and Zouali group (26)
  • Identification of increased levels of antibodies to this region in lupus patients by Shearer/Mozes group (27)
  • Collaborative isolation of potent HIV neutralizing antibodies to this region from lupus patients by Paul group and Hanson group (28), identification of abzymes to this region by Paul group (29,30).
  • Discovery of abzymes and reversibly binding antibodies to 421-433 gp120 region in blood of long-term survivors of HIV infection by Paul group (31)
  • Demonstration of neutralization of genetically diverse HIV strains by these antibodies by Hanson group and independent verification of neutralizing activity by Montefiori group and  Ochsenbauer group (31, unpublished) – designation of the 421-433 region as the Achilles heel of HIV
  • Antibodies made available for non-profit research entities by Paul group

Covalent vaccination approach

  • Covalent immunization shown to induce abzymes and abzyme-like antibodies to HIV by Paul group (32-34)
  • Similar covalent immunization approach independently used by others to induces abzymes with serine esterase (35) and aldolase-like  (36) enzymatic activities
  • Prototype vaccine that induced HIV neutralizing abzymes-like antibodies directed to the 421-433 Achilles heel of HIV developed by Paul group (37)
  • HIV neutralization by prototype vaccine-induced antibodies verified independently by Hanson group, Montefiori group (cited in ref 37) and Ochsenbauer group (unpublished)
  • Task ahead: Effective HIV vaccination by focusing the immune response at the Achilles heel, maximizing the abzyme response (38)