Scientific Publications by FDA Staff

J Virol 2018 Aug 16;92(17):e00976-18

Newcastle disease virus-based vectored vaccine against poliomyelitis.

Viktorova EG, Khattar SK, Kouiavskaia D, Laassri M, Zagorodnyaya T, Dragunsky E, Samal S, Chumakov K, Belov GA

Poliovirus eradication initiative spawned global immunization infrastructure and dramatically decreased the disease, yet the original virus eradication goal has not been met. The suboptimal properties of the existing vaccines are among the major reasons why the program repeatedly missed eradication deadlines. Oral live poliovirus vaccine (OPV), while affordable and effective, occasionally causes the disease in the primary recipients, and the attenuated viruses rapidly regain virulence and can cause poliomyelitis outbreaks. Inactivated poliovirus vaccine (IPV) is safe, but expensive, and does not induce mucosal immunity necessary to interrupt the virus transmission. While the need for a better vaccine is widely recognized, the current efforts are largely focused on improvements of OPV or IPV still beset by the fundamental drawbacks of the original products. Here we demonstrate a different design of anti-poliovirus vaccine based on in situ production of virus-like particles (VLPs). Poliovirus capsid protein precursor together with a protease required for its processing are expressed from a Newcastle Disease virus (NDV) vector, a negative strand RNA virus with mucosal tropism. In this system polio VLPs are produced in the cells of vaccine recipients and presented to their immune system in the context of active NDV replication, serving as a natural adjuvant. Intranasal administration of the vectored vaccine to guinea pigs induced strong neutralizing systemic and mucosal antibody response. Thus, vectored poliovirus vaccine combines the affordability and efficiency of a live vaccine with absolute safety, since no full-length poliovirus genome is present at any stage of the vaccine life cycle. IMPORTANCE: A new safe and effective anti-poliovirus vaccine is urgently needed not only to complete the eradication but also to be used in the future to prevent possible virus re-emergence in a post-polio world. Currently, new formulations of oral vaccine as well as improvements of inactivated vaccine are being explored. Here we designed a viral vector with mucosal tropism, which expresses poliovirus capsid proteins. Thus, polio virus-like particles are produced in vivo, in the cells of a vaccine recipient, and are presented to the immune system in the context of vector virus replication, stimulating the development of systemic and mucosal immune responses. Such approach allows the development of an affordable and safe vaccine, which does not rely on full-length poliovirus genome at any stage.