Control of early HIV-1 infection associates with plasmacytoid dendritic cell-reactive opsonophagocytic IgG antibodies to HIV-1 p24.
We have previously demonstrated that HIV-1 p24-specific plasmacytoid dendritic cell-reactive opsonophagocytic antibody (PROAb) responses associate with control of chronic HIV infection. Here, we examined whether HIV-1 p24-specific PROAbs associate with control of early HIV infection and their relationship with HIV-1 p24-specific IgG subclasses.



Plasma collected at 8 and 52 weeks following primary HIV-1 infection was obtained from antiretroviral therapy-naïve patients who were classified as 'good' (plasma HIV-1 RNA < 5000 copies/ml; n = 17) or 'poor' (HIV-1 RNA > 50 000 copies/ml; n = 15) controllers at week 52. HIV-1 p24-specific PROAb responses were assayed using a plasmacytoid dendritic cell line (Gen2.2), and HIV-1 p24-specific IgG3, IgG1 and IgG2 levels were assayed by ELISA.



HIV-1 p24-specific PROAb responses increased in 'good controllers' (P = 0.01) but remained unchanged in 'poor controllers' between weeks 8 and 52. Of the HIV-1 p24-specific IgG subclasses measured, only IgG1 increased over this time period in 'good controllers' alone (P = 0.003), which correlated with the increase in HIV-1 p24-specific PROAb responses (r = 0.83, P < 0.0001). Depletion of IgG1 from IgG preparations of 'good controllers' resulted in the inhibition of HIV-1 p24-specific PROAb responses. In the total patient cohort, plasma HIV-1 RNA levels at week 52 correlated inversely with changes in HIV-1 p24-specific PROAb responses (r = -0.37, P = 0.04) and IgG1 (r = -0.51, P = 0.003) levels between weeks 8 and 52.



Control of early HIV-1 infection was associated with an increase in HIV-1 p24-specific PROAb responses, which was mediated by HIV-1 p24-specific IgG1 antibodies. These findings provide further evidence that antibodies to HIV core proteins may contribute to control of HIV-1 infection.
aSchool of Pathology and Laboratory Medicine, University of Western Australia, Perth bThe Kirby Institute, University of New South Wales, Sydney cStem Cell Unit, Institute of Respiratory Health dCentre for Respiratory Health, School of Medicine and Pharmacology, University of Western Australia eDepartment of Microbiology and Infectious Diseases, Royal Perth Hospital, Perth fPathWest Laboratory Medicine gDepartment of Clinical Immunology, Royal Perth Hospital, Perth, Australia.
M Christian
MC
Tjiam
Lucy
L
Sariputra
Jesse D
JD
Armitage
James P A
JP
Taylor
Anthony D
AD
Kelleher
Dino B A
DB
Tan
Silvia
S
Lee
Sonia
S
Fernandez
Martyn A
MA
French
D000328:Adult; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000097:blood*; D016655:HIV Core Protein p24 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D009895:Opsonin Proteins / Q000097:blood*; D010587:Phagocytosis; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
D015483:HIV Antibodies; D016655:HIV Core Protein p24; D007074:Immunoglobulin G; D009895:Opsonin Proteins; D012367:RNA, Viral