Vaccine-induced IgG2 anti-HIV p24 is associated with control of HIV in patients with a 'high-affinity' FcgammaRIIa genotype.
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.
French
Martyn A
MA
School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia. martyn.french@uwa.edu.au
Tanaskovic
Sara
S
Law
Matthew G
MG
Lim
Andrew
A
Fernandez
Sonia
S
Ward
Larry D
LD
Kelleher
Anthony D
AD
Emery
Sean
S
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
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