Human HIV vaccine trials: does antibody-dependent enhancement pose a genuine risk?

Antibody-dependent enhancement is a general in vitro property of enveloped viruses. In certain circumstances, antibody-dependent enhancement is a bona fide pathophysiologic mechanism in vivo. There are several examples of virus disease of humans and animals in which incomplete or partial immunity can lead to enhanced infection and/or disease. In some cases, this appears to be attributable to antibody-dependent enhancement. Conversely, there are several examples of viruses for which in vitro antibody-dependent enhancement has been demonstrated, but for which vaccines have been used safely in millions of persons for decades. Finally, antibody-dependent enhancement of HIV is a genuine concern. However, to date there is no direct clinical, experimental, or epidemiological evidence that HIV enhancement can be operative in vivo. Such evidence should be actively sought.