12:00 AM
Nov 14, 2013
 |  BC Innovations  |  Targets & Mechanisms

RSVing for site zero

Despite decades of research, respiratory syncytial virus (RSV) remains a highly prevalent childhood pathogen without an approved vaccine.1 There is a marketed prophylactic-Synagis palivizumab-to prevent severe disease caused by RSV in at-risk infants, but the passive immunization provided by the antibody does not last from season to season, and its high cost precludes its use in other patient populations. Now, a team from the NIH has used structure-based design to generate RSV vaccines that showed strong neutralizing activity in both mice and macaques.2

The next step is picking a lead vaccine to advance into GMP production and clinical trials.

RSV is the most common cause of hospitalization in children under 5 years of age and results in more than 3 million hospital stays each year. RSV mortality in the elderly is comparable to that of influenza virus.3,4

There are multiple barriers to developing RSV vaccines. These include the very young age of most patients, the lack of a good animal model that recapitulates human RSV infection, and the virus' ability to both evade innate and adaptive immunity and reinfect patients.

The most substantial barrier came to light decades ago when one of the first candidate vaccines-formalin-inactivated RSV (FI-RSV)-not only failed to protect children in early trials but also enhanced virus-induced respiratory disease and led to two deaths and a high hospitalization rate.

The vaccine-enhanced disease is thought to be caused by the induction of high levels of non-neutralizing antibodies.

Ideally, an effective vaccine would induce high levels of neutralizing antibodies.

Synagis is marketed by AstraZeneca plc's MedImmune LLC unit to prevent RSV in premature infants at high risk of infection. The humanized mAb targets RSV F, which is a trimeric glycoprotein the virus uses to enter host cells via membrane fusion. The mAb posted sales of $1.04 billion in 2012.

Although RSV F is clearly a good starting point for vaccine development, the conformational diversity of the target makes engineering a good antigen difficult.

Before virus-cell interactions, RSV F exists in an...

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