Traitors of the immune system-enhancing antibodies in HIV infection: their possible implication in HIV vaccine development

Abstract

Considering recent HIV vaccine failures, the authors believe that it would be most important to find new targets for vaccine-induced immunity, and to analyze the data from previous trials, using an innovative approach. In their review article, the authors briefly summarize the significance of the antibody-dependent enhancement of infection in different viral diseases and discuss role of these types of antibodies as the obstacles for vaccine development. Findings which indicate that complement-mediated antibody-dependent enhancement (C-ADE) is present also in HIV-infected patients, are summarized. Previous results of the authors, suggesting that C-ADE plays a very important role in the progression of HIV infection are described. Data reflecting that enhancing antibodies may develop even in vaccinated animals and human volunteers, and may be responsible for the paradoxical results obtained in some subgroups of vaccinees are discussed. Finally, based on their hypothesis, the authors offer some suggestions for the future development of vaccines.

Figure 1

Temporal changes of enhancement/neutralization index (E/NI) values, HIV-1 antigen, antibody and RNA levels in a HIV-1 seroconversion panel. Enhancement/neutralization index values in MT-4 cell cultures infected with mixtures of HIV-1IIIB, 1:64 dilutions of recalcified and heat-treated samples supplemented with pooled serum from HIV-seronegative subjects as complement source (○– – – – –○) are shown on the left y-axis. HIV antibody titers measured by the Abbott HIV 1/2 kit (■– – – – – –■), the level of p24 antigen determined by the Abbott antigen test {●---------●) expressed in both cases in sample OD/cut-off OD (s/co) values are shown on the right y-axis. HIV RNA levels (+, detectable; −, undetectable are also shown. Adapted from .

Figure 2

Correlation of virus neutralization/enhancement measured in the presence of complement with plasma HIV-1 RNA (Amplicor). P value for Kruskall–Wallis test is indicated. Adapted from .

Figure 3

Development of AIDS during a 61 (55–64) months median (IQ range) follow-up period in 21 asymptomatic HIV patients with different baseline neutralization in the presence of complement. P value for Fisher's exact test is indicated. Adapted from .

Figure 4

Distribution of samples with neutralization (E/N index < 0.5), neither neutralization nor enhancement (E/N index 0.5–2.0), or enhancement (E/N index > 2.0) measured in the presence of complement in the same 28 AIDS patients at the beginning of and after the administration of HAART for 19.0 (10.5–24.0) months. P value for χ² test is indicated. Adapted from .