Detection of Antibody-Dependent Complement-Mediated Inactivation of both Autologous and Heterologous Virus in Primary Human Immunodeficiency Virus Type 1 Infection

Abstract

Specific CD8 T-cell responses to human immunodeficiency virus type 1 (HIV-1) are induced in primary infection and make an important contribution to the control of early viral replication. The importance of neutralizing antibodies in containing primary viremia is questioned because they usually arise much later. Nevertheless antienvelope antibodies develop simultaneously with, or even before, peak viremia. We determined whether such antibodies might control viremia by complement-mediated inactivation (CMI). In each of seven patients studied, antibodies capable of CMI appeared at or shortly after the peak in viremia, concomitantly with detection of virus-specific T-cell responses. The CMI was effective on both autologous and heterologous HIV-1 isolates. Activation of the classical pathway and direct viral lysis were at least partly responsible. Since immunoglobulin G (IgG)-antibodies triggered the CMI, specific memory B cells could also be induced by vaccination. Thus, consideration should be given to vaccination strategies that induce IgG antibodies capable of CMI.

Preclinical Studies of Human Immunodeficiency Virus/AIDS Vaccines: Inverse Correlation between Avidity of Anti-Env Antibodies and Peak Postchallenge Viremia

“…Thus, unlike neutralizing Ab, which is largely isolate specific, high-avidity Ab may be capable of blunting acute viremia for a diversity of isolates. This is consistent with studies on Fc-and complement-mediated virolysis and cytolysis that have demonstrated that patient serum mediating these activities recognizes a range of Envs (1,2,5,12,18,32,35). Our studies also show that not all clade B Envs elicit high-avidity Ab for incident clade B isolates.…”

“…The correlation held for the avidity of the Ab at the time of challenge as well as the avidity of the Ab at 3 weeks postchallenge. We suggest that avidity correlated with protection because it facilitated the initiation by bound Ab of Fc-mediated mechanisms of viral control such as complement-mediated lysis (1,14,35), antibody-dependent cellular cytotoxicity (2,8,12,30,37), antibody-dependent cell-mediated virus inhibition (11), and phagocytosis. Presumably the more tightly Ab bound to Env on virions and infected cells, the more effective it was at initiating Fc-mediated mechanisms of virus control.…”

A high affinity inhibitor of human CD59 enhances complement-mediated virolysis of HIV-1: Implications for treatment of HIV-1/AIDS

“…3). These endogenous anti-HIV-1 Abs developed by HIV-1-infected individuals in both the acute and chronic phases of infection activate complement through the classical pathway, as indicated by published reports that C1q-deficient serum as a source of complement fails to induce anti-HIV-1 Ab-mediated virolysis (45). Fig.…”

Matrix Metalloprotease Inhibitors Restore Impaired NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Human Immunodeficiency Virus Type 1 Infection

“…In the context of HIV infection, antibody (Ab)-dependent cellular cytotoxicity (ADCC) independently correlates with differences in HIV disease course (14). Levels of Abs that are able to activate NK cells to mediate ADCC are elevated in the plasma of subjects who have nonprogressive disease and are diminished in subjects with progressive infection (2,14,15,30,43) and are detectable as early as a few weeks postinfection (1,13). Interestingly, Hessell et al demonstrated a critical role of ADCC in the protection of monkeys from infection following passive infusion of the neutralizing Ab B12 lacking the capacity to engage Fc receptors, suggesting that ADCC may play a critical role in protection from both disease acquisition and progression (21).…”