Vaccines: New Generation of Inactivated Poliovirus Vaccines for Universal Immunization after Eradication of Poliomyelitis

ArticleinClinical Infectious Diseases 47(12):1587-92 · January 2009with11 Reads
DOI: 10.1086/593310 · Source: PubMed
Abstract
Twenty years of global polio eradication efforts may soon eliminate the transmission of wild-type poliovirus. However, new information that has been learned about poliovirus, as well as the political realities of a modern world, demand that universal immunity against poliomyelitis be maintained, even after wild-type poliovirus is eradicated. Although 2 excellent vaccines have proven to be highly effective in the past, neither the live-attenuated vaccine nor the currently used inactivated vaccine are optimal for use in the posteradication era. Therefore, concerted efforts are urgently needed to develop a new generation of vaccine that is risk-free and affordable and can be produced on a global scale. Here, we discuss the desired properties of a vaccine and methods to create a new polio vaccine.
    • "The formalin-inactivated PV vaccine (IPV), developed by Salk et al. (1954), was the first vaccine to be licensed followed by the oral PV vaccine (OPV) developed by Sabin (1957). The last decade saw an increase in the use of IPV as compared to OPV which was due to the excellent safety and efficacy record of IPV as well as cost-effective production process for its production (Chumakov and Ehrenfeld, 2008). Even though IPV is less effective in stimulating enteric immunity than live vaccine. "
    [Show abstract] [Hide abstract] ABSTRACT: The inactivated polio vaccine (IPV) contains poliovirus (PV) samples that belong to serotypes 1, 2 and 3. All three serotypes contain the D-antigen, which induces protective antibodies. The antigenic structure of PVs consists of at least four different antigenic sites and the D-antigen content represents the combined activity of multiple epitopes (Ferguson et al., 1993; Minor, 1990; Minor et al., 1986). The potency of IPV vaccines is determined by measuring the D-antigen content. Several ELISA methods have been developed using polyclonal or monoclonal antibodies (Mabs) in order to quantify the D-antigen content. Characterization of the epitopes recognized by the different Mabs is crucial to map the entire virus surface and ensure the presence of epitopes able to induce neutralizing antibodies. Using a new approach that we developed to study the interaction between monoclonal antibodies and poliovirus type 2, which combines cryo-electron microscopy, image analysis and X-ray crystallography along with identification of exposed amino acids, we have mapped in 3D the epitope sites recognized by three specific Fabs at the surface of poliovirus type 2 (PV2) and characterized precisely the antigenic sites for these Fabs. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jun 2015
    • "The formalin-inactivated PV vaccine (IPV), developed by Salk et al. (1954), was the first vaccine to be licensed followed by the oral PV vaccine (OPV) developed by Sabin (1957). The last decade saw an increase in the use of IPV as compared to OPV which was due to the excellent safety and efficacy record of IPV as well as cost-effective production process for its production (Chumakov and Ehrenfeld, 2008). The IPV is formulated as a trivalent product containing a representative virus isolate of each serotype (Mahoney, MEF-1 and Saukett). "
    [Show abstract] [Hide abstract] ABSTRACT: The inactivated polio vaccine (IPV) contains poliovirus (PVs) samples that belong to serotypes 1, 2 and 3. All three serotypes contain the D-antigen, which induces protective antibodies. The antigenic structure of PVs consists of at least four different antigenic sites and the D-antigen content represents the combined activity of multiple epitopes (Ferguson et al., 1993; Minor, 1990; Minor et al., 1986). The potency of IPV vaccines is determined by measuring the D-antigen content. Several ELISA methods have been developed using polyclonal or monoclonal antibodies (Mabs) in order to quantify the D-antigen content. Characterization of the epitopes recognized by the different Mabs is crucial to map the entire virus surface and ensure the presence of epitopes able to induce neutralizing antibodies. In a new approach, combining cryo-electron microscopy and image analysis with X-ray crystallography data available along with identification of exposed amino acids we have mapped in 3D the epitope sites recognized by five specific Fabs and one Mab and characterized precisely the antigenic sites for these Mabs. We propose this method to be used to map the entire “epitopic” surface of virus.
    Full-text · Article · Dec 2014
    • "One significant disadvantage of OPV, however, is that in rare cases (about 1 in 0.9 million vaccinees, [11]), an attenuated strain in OPV can revert to virulence and cause vaccine-associated paralytic poliomyelitis (VAPP). The use of OPV may also lead to vaccine-derived polioviruses (VDPVs) capable of spread between individuals1213141516. Another disadvantage of OPV, is that in its trivalent form the three vaccine strains compete with one another to infect the gut, resulting in a stronger immune response to type 2 versus types 1 and 3 [17]. "
    [Show abstract] [Hide abstract] ABSTRACT: The eradication of poliovirus from the majority of the world has been achieved through the use of two vaccines: the inactivated poliovirus vaccine (IPV) and the live-attenuated oral poliovirus vaccine (OPV). Both vaccines are effective at preventing paralytic poliomyelitis, however, they also have significant differences. Most importantly for this work is the risk of revertant virus from OPV, the greater cost of IPV, and the low mucosal immunity induced by IPV. We and others have previously described the use of an alphavirus-based adjuvant that can induce a mucosal immune response to a co-administered antigen even when delivered at a non-mucosal site. In this report, we describe the use of an alphavirus-based adjuvant (GVI3000) with IPV. The IPV-GVI3000 vaccine significantly increased systemic IgG, mucosal IgG and mucosal IgA antibody responses to all three poliovirus serotypes in mice even when administered intramuscularly. Furthermore, GVI3000 significantly increased the potency of IPV in rat potency tests as measured by poliovirus neutralizing antibodies in serum. Thus, an IPV-GVI3000 vaccine would reduce the dose of IPV needed and provide significantly improved mucosal immunity. This vaccine could be an effective tool to use in the poliovirus eradication campaign without risking the re-introduction of revertant poliovirus derived from OPV.
    Full-text · Article · Dec 2013
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