Current concepts and progress in RSV vaccine development

Abstract

Respiratory syncytial virus (RSV) disease is an important cause of morbidity and mortality in children and debilitated adults and remains one of the major global unmet challenges for vaccine development. Several immunological issues have delayed the development of vaccines, especially the poorly protective response to natural infection and the enhancement of disease following administration of formalin inactivated vaccines during trials conducted in the 1960s. Advances in knowledge of the immune system, of the virus and its antigenic properties combined with new vaccine technologies are now injecting new hope into the field and have given rise to many promising vaccine approaches. Some of these may be optimal for use in children, while others may be more appropriate for pregnant women or vulnerable older adults. With a multi-pronged approach to prevention, we propose that it may be possible to destabilise community circulation of RSV and thus to significantly lessen the impact of RSV disease.

Figure 1. Targeting different populations with immune interventions against respiratory syncytial virus (RSV).

Multiple checkpoints may be targeted for the interruption of RSV infection. At-risk individuals may be protected directly through induction of protective immunity or indirectly via reduced circulation of infection in the community. Vaccination of healthy individuals aims to promote herd immunity and/or prevent transmission between school-aged children and adults with whom they are in contact. This would interrupt the amplification loop within households, hospitals and schools, reducing transmission to vulnerable populations (i.e., neonates, immunosuppressed individuals and the elderly). Vaccination of pregnant women during the last trimester aims to enhance maternofetal transfer of IgG to protective levels in term infants, but passive vaccination would probably still be required for preterm infants or immunosuppressed adults. Inactive or subunit RSV vaccines are most appropriate for RSV-experienced individuals in whom the risk of vaccine-enhanced disease is low. Live attenuated vaccines are likely to be safe in children, and the induction of mucosal immunity would have the added benefit of reducing virus shedding.

Figure 2. Vaccines currently in development against human respiratory syncytial virus infection.

Many candidate vaccines are at preclinical stage. However, there is live attenuated, particle-based, subunit and gene-based vectors being tested at Phase I or II trials. The respiratory syncytial virus vaccine snapshot is reproduced with permission from PATH and can be found at [84]. Reproduced with permission from the PATH [101].