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133 Antibody from Patients with Acute HIV Infection Inhibits Primary Strains of HIV-1 in the Presence of Natural Killer Effector Cells
D. N. Forthal*1, G. Landucci1, and E. S. Daar2
1Univ. of California, Irvine, USA and 2Cedars-Sinai/UCLA, Los Angeles, CA, USA
Background: The partial control of viremia during acute HIV infection is accompanied by a cytotoxic T-lymphocyte (CTL) response and an absent or infrequent neutralizing antibody response. The control of HIV-1 viremia has thus been attributed primarily, if not exclusively, to CTL activity. In this study, the role of antibody in controlling viremia was investigated by measuring the ability of plasma from acutely infected patients to inhibit primary strains of HIV-1 in the presence of natural killer (NK) effector cells.
Methods: Plasma was collected from 15 patients between 3 and 56 days (median = 18 days) following onset of symptoms of acute HIV infection. Patient or control plasma (1:10 dilution), with or without NK effector cells from a healthy donor (E:T=10:1), was added to CD4+ lymphocytes infected for 48 h with a primary strain of HIV-1. Supernatant fluid was assayed for p24 at various times.
Results: Compared with uninfected controls, plasma from 8/15 acutely infected patients inhibited virus by >50% in the presence of NK effector cells, and 5 of these inhibited by >90%; the magnitude of virus inhibition was inversely associated with plasma HIV RNA level. The anti-viral activity was minimal or undetectable in the absence of NK effector cells, was contained within the IgG fraction, required intact antibody (rather than Fab), and was directed against HIV glycoproteins. Furthermore, both autologous and heterologous primary HIV-1 strains were inhibited. Finally, antibody from acutely infected patients likely reduced HIV-1 yield in vitro both by mediating effector cell lysis of target cells expressing HIV-1 glycoproteins and by augmenting the release of b-chemokines from NK cells.
Conclusions: An effector-cell-mediated, anti-viral antibody response occurs within days to weeks after symptom onset in acute HIV infection. HIV-1-specific antibody may therefore be an important contributor to the early control of viremia, and the antigens that elicit this response may be important components of an HIV vaccine.
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