Development of Mucosal Inactivated Vaccine against Poliomyelitis
Tech Area / Field
3 Approved without Funding
State Research Center of Virology and Biotechnology VECTOR, Russia, Novosibirsk reg., Koltsovo
- Research Institute of Viral Preparations, Russia, Moscow
- University of Tokyo / Graduate School of Medicine, Japan, Tokyo\nVanderbilt University Medical Center / Department of Pediatrics, USA, TN, Nashville
Project summaryIn 1988, the World health Assembly adopted the decision on a complete eradication of poliomyelitis in the world. Since that time, the campaign against poliomyelitis headed by the World Health Organization (WHO) has achieved considerable results. By the end of 2002, only four countries remained where paralytic poliomyelitis cases are still recorded, whereas the majority of regions, such as North and South America, Europe, Australia, and Pacific region, are certified as free from viral poliomyelitis.
However, although rather rarely, cases of the so-called vaccine-associated poliomyelitis are yet reported in all the countries using live polio vaccine (LPV) against poliomyelitis. The vaccine-associated poliomyelitis is caused by revertants of LPV strains emerging in organisms of vaccinated children. This disease is reported for both vaccinees themselves and contact cases. In the countries using inactivated polio vaccine (IPV), no vaccine-associated poliomyelitis cases are recorded. Moreover, recent data demonstrate that vaccine-like revertants may potentially cause not only single cases of paralytic poliomyelitis, but also small epidemics in the regions with insufficient population immunity to the pathogen.
It is presumed that LPV will be used in the majority of countries until a complete eradication of poliomyelitis worldwide. Even after the complete global eradication of viral paralytic poliomyelitis, it is planned to continue the vaccination until 2010. Usually, a sufficiently high immunity to all the three poliovirus serotypes retains up to 20 years. However, upon cessation of the vaccination, several million children will be born with a completely absent immunity to poliomyelitis. Thus, emergence of a virulent poliovirus in the population several years after vaccination cessation will with a high probability cause an epidemic.
At least two ways may lead to emergence of such virulent poliovirus. One of the ways is bioterrorism or release of the virus from a laboratory. WHO is now detecting all the laboratories using either virulent strains or revertants of polioviruses aiming to decrease the number of such laboratories. However, the RNA genome of poliovirus is infectious, the genomic sequences of poliovirus infectious strains are known and published, any laboratory possessing the corresponding equipment, and reagents may be capable of synthesizing the viral RNA artificially to obtain the infectious virulent poliovirus. The second way is emergence of vaccine-like revertants of poliovirus vaccine strains. It was demonstrated recently that vaccine polioviruses were capable of rather long-term persistence (2 to 10 years) in LPV vaccinees with primary impairments of the immune system. During the persistence, vaccine viruses revert, which confer them capable of causing paralytic poliomyelitis. Here, we encounter the problem of how to halt spread of poliomyelitis epidemic in the case such situation occurs after vaccination against poliomyelitis is ceased on the background of a sufficient population cohort lacking immunity to this virus.
As is known, intestinal mucosa is the main site where polioviruses reproduce in human body. There are published data on the ability of vaccine poliovirus strains to interfere and displace virulent strains of the virus from human intestines. However, the major specific feature of the vaccine strains constituting LPV is the ability to induce local intestinal immunity, thereby decreasing drastically spread of the virulent virus in the population. On the other hand, the ability of IPV to induce local intestinal immunity and, consequently, limit the spread of polioviruses is rather insignificant. In the countries using IPV for struggle against poliomyelitis, the virulent virus is capable of being transmitted among vaccinees without causing any disease. However, when the virus will “find”, for example, a village where the population has not been vaccinated due to religious sanctions, the poliomyelitis epidemic is guaranteed.
Thus, neither live nor inactivated polio vaccines are optimal for suppressing outbreaks or epidemics of poliomyelitis upon cessation of vaccination. Presumably, the optimal preparations for this purpose would be the IPV capable of inducing local intestinal immunity, that is, mucosal IPV. It has been recently demonstrated using a number of candidate vaccines that intranasal administration of conventional inactivated antiviral vaccines or viral antigens in combination with mucoadhesive adjuvants induce not only a good production of humoral antibodies, but also local immunity in mucosae, including intestinal and nasal mucosae, because the mucosae have common immune system. Numerous biological and chemical preparations displaying mucoadhesive properties have been so far examined. These preparations may either be directly introduced into the inactivated vaccines or used for construction of biodegradable microcapsules (microgranules). Presumable, a mucosal IPV containing mucoadhesive adjuvants and administered intranasally or orally is capable of inducing not only humoral, but also local immunity in intestinal mucosa, the main place where the virus propagates, thereby limiting spreading of poliovirus.
Thus, the goal of the project is to develop a mucosal inactivated polio vaccine for oral administration that would be capable of inducing local intestinal immunity in addition to humoral and cell-mediated immunities.
Solution of the problems stated will allow for development of mucosal inactivated polio vaccine capable of inducing not only local, but also local intestinal immunity and, therefore, limit spread of the virus in case of possible poliomyelitis outbreak, especially upon cessation of the vaccination against poliomyelitis
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