One HIV vaccine trial provided some small measure of hope for the development of an effective HIV vaccine. This vaccine, known as RV144, was administered to a high risk population in Thailand, and reduced new infections by ~30%. To address the mechanism of immune protection correlating with vaccine efficacy, a series of studies were performed. In one study, total IgG antibodies from four non-infected vaccinees were isolated and were mixed with HIV-infected cells plus peripheral blood lymphocytes from healthy unrelated donors. As a control, IgG antibodies were purified from four donors receiving the placebo, rather than the RV144 vaccine. Six hours later, lysis of the HIV-infected target cells was assessed, as shown in Figure Q40). Figure Q40) The immune mechanism that correlates with protection based on these data is:
A) CD8-dependent target cell lysis
B) Complement-dependent cell lysis
C) Induction of apoptosis by TNF-R stimulation
D) Target cell apoptosis induced by Fas-ligand stimulation
E) ADCC induced by NK cells

Question

One HIV vaccine trial provided some small measure of hope for the development of an effective HIV vaccine. This vaccine, known as RV144, was administered to a high risk population in Thailand, and reduced new infections by ~30%. To address the mechanism of immune protection correlating with vaccine efficacy, a series of studies were performed. In one study, total IgG antibodies from four non-infected vaccinees were isolated and were mixed with HIV-infected cells plus peripheral blood lymphocytes from healthy unrelated donors. As a control, IgG antibodies were purified from four donors receiving the placebo, rather than the RV144 vaccine. Six hours later, lysis of the HIV-infected target cells was assessed, as shown in Figure Q40).  Figure Q40) The immune mechanism that correlates with protection based on these data is:
A) CD8-dependent target cell lysis 
B) Complement-dependent cell lysis 
C) Induction of apoptosis by TNF-R stimulation 
D) Target cell apoptosis induced by Fas-ligand stimulation 
E) ADCC induced by NK cells

Quizplus · Accepted Answer

The experiment described in the question involves measuring cell lysis caused by IgG antibodies from individuals vaccinated with the RV144 HIV vaccine. The lysis is measured by monitoring the release of intracellular enzymes (lactose dehydrogenase) into the culture medium. The data show that there is a statistically significant increase in cell lysis when the IgG antibodies from vaccinated individuals were added, but not when antibodies from placebo recipients were added. This suggests that the antibodies from vaccinated individuals have the ability to bind to HIV-infected cells and recruit natural killer (NK) cells to kill them via antibody-dependent cell-mediated cytotoxicity (ADCC). Therefore, the immune mechanism that correlates with protection in RV144 vaccine recipients is ADCC induced by NK cells.

One HIV Vaccine Trial Provided Some Small Measure of Hope