title: Spontaneous development of IgM anti-cocaine antibodies in habitual cocaine users: effect on IgG antibody responses to a cocaine cholera toxin B conjugate vaccine.
abstract: OBJECTIVE
  In cocaine vaccine studies, only a minority of subjects made strong antibody responses. To investigate this issue, IgG and IgM antibody responses to cocaine and to cholera toxin B (CTB-the carrier protein used to enhance immune responses to cocaine) were measured in sera from the 55 actively vaccinated subjects in a Phase IIb randomized double-blind placebo-controlled trial (TA-CD 109).
  
  
  METHODS
  Isotype specific ELISAs were used to measure IgG and IgM anti-cocaine and anti-CTB antibody in serial samples collected prior to and at intervals after immunization. We assessed IgG anti-cocaine responses of patients with pre-vaccination IgM anti-cocaine antibodies. Competitive inhibition ELISA was used to evaluate antibody specificity.
  
  
  CONCLUSIONS
  Before immunization, 36/55 subjects had detectable IgM antibodies to cocaine, and 9 had IgM levels above the 95% confidence limit of 11 μg/ml. These nine had significantly reduced peak IgG anti-cocaine responses at 16 weeks, and all were below the concentration (40 μg/ml) considered necessary to discourage recreational cocaine use. The IgG anti-CTB responses of these same subjects were also reduced.
  
  
  CONCLUSIONS
  Subjects who develop an IgM antibody response to cocaine in the course of repeated recreational exposure to this drug are significantly less likely to produce high levels of IgG antibodies from the cocaine conjugate vaccine. The failure may be due to recreational cocaine exposure induction of a type 2 T-cell independent immune response. Such individuals will require improved vaccines and are poor candidates for the currently available vaccine.
authors: Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX 77030, USA. forson@bcm.edu
authors: Frank M
authors: FM
authors: Orson
authors: Roger D
authors: RD
authors: Rossen
authors: Xiaoyun
authors: X
authors: Shen
authors: Angel Y
authors: AY
authors: Lopez
authors: Yan
authors: Y
authors: Wu
authors: Thomas R
authors: TR
authors: Kosten
mesh_terms: D000918:Antibody Specificity / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology*; D022121:Cholera Vaccines / Q000276:immunology*; D003042:Cocaine / Q000276:immunology*; D019970:Cocaine-Related Disorders / Q000097:blood / Q000276:immunology*; D004311:Double-Blind Method; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*
chemical_list: D022121:Cholera Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D002772:Cholera Toxin; D003042:Cocaine