Antibody responses to filovirus infections in humans: protective or not?

Disease outbreaks caused by Ebola virus and other filoviruses highlight the urgent need for an in-depth understanding of the role of antibody responses in recovery. In this Personal View we aim to discuss the controversial biological role of antibodies during natural filovirus infections in humans. Survival during natural human filovirus infections correlates with the magnitude of the process of antibodies binding to the filovirus glycoprotein and neutralising the virus. Despite the severity of the disease, highly potent monoclonal antibodies have been isolated from survivors of natural filovirus infections, suggesting that the magnitude of the antibody response is insufficient for prevention of severe disease. Unlike natural infections, filovirus vaccines, which express the viral glycoprotein, do induce protective concentrations of antibodies, albeit only when administered at very high doses. Multiple mechanisms by which filoviruses can delay and reduce the antibody response have been identified in the past decade. Furthermore, subneutralising antibody concentrations have been shown to enhance filovirus infections of immune cells bearing Fc receptors. Understanding the role of antibody responses during natural filovirus infections is important for the development of safe and potent vaccines and antibody-based treatments.