title: Vaccine-induced IgG2 anti-HIV p24 is associated with control of HIV in patients with a 'high-affinity' FcgammaRIIa genotype.
abstract: OBJECTIVE
  We have previously shown that vaccination with a recombinant fowlpox virus carrying the genes for HIV Gag-Pol and interferon-gamma (IFN-gamma) was associated with partial control of HIV replication after antiretroviral therapy (ART) was ceased but not with increased anti-HIV T-cell responses. Because IFN-gamma enhances IgG2 production, and IgG2 antibodies to HIV antigens and the 'high-affinity' polymorphism of FcgammaRIIa (the major Fc receptor for IgG2) have been associated with a favourable outcome of HIV infection, we examined the association of IgG2 antibodies to HIV p24 and 'high-affinity' polymorphisms of FcgammaRIIa with control of HIV replication in these patients.
  
  
  METHODS
  Plasma from weeks 0 (cessation of ART 1 week after the last vaccination), 9 and 20 was available from patients who had received the full construct vaccine, a partial construct (without IFN-gamma) or placebo. IgG2 and IgG1 anti-p24 and anti-gp41 were assayed and all patients were genotyped for the FcgammaRIIa 131 R/H polymorphism that affects IgG2 binding.
  
  
  RESULTS
  At week 0, IgG2 anti-p24 was present in five of nine full construct patients but none of 14 partial construct or placebo patients and was associated with a smaller increase in plasma HIV RNA over 20 weeks. Patients with IgG2 anti-p24 and the 'high-affinity' polymorphism of FcgammaRIIa exhibited lower HIV replication than other patients at week 20.
  
  
  CONCLUSIONS
  The role of IgG2 anti-HIV antibodies and FcgammaRIIa in the control of HIV replication should be investigated further. Inclusion of an IFN-gamma gene in DNA vaccine constructs might be a means of enhancing IgG2 antibody production.
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia. martyn.french@uwa.edu.au
authors.forename: Martyn A
authors.initials: MA
authors.lastname: French
authors.forename: Sara
authors.initials: S
authors.lastname: Tanaskovic
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Law
authors.forename: Andrew
authors.initials: A
authors.lastname: Lim
authors.forename: Sonia
authors.initials: S
authors.lastname: Fernandez
authors.forename: Larry D
authors.initials: LD
authors.lastname: Ward
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D005587:Fowlpox virus / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D005838:Genotype; D015483:HIV Antibodies / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D019562:Viral Load
chemical_list: D016915:AIDS Vaccines; C080568:Fc gamma receptor IIA; D015683:Gene Products, gag; D015684:Gene Products, pol; D015483:HIV Antibodies; D007074:Immunoglobulin G; D017452:Receptors, IgG