High-titred neutralizing antibodies to human enterovirus 71 preferentially bind to the N-terminal portion of the capsid protein VP1

Abstract

Human enterovirus 71 has emerged as an important pathogen of children in the Asia Pacific region, and it may be important to consider the development of a vaccine against this virus. Human cord serum was used as a source of neutralizing antibodies to determine whether the N- or C-terminal half of the VP1 capsid protein was more likely to harbour neutralizing determinants. Cord sera from 205 individuals were tested for neutralizing antibodies against human enterovirus 71 in an indirect ELISA against recombinant VP1 antigen as well as the N- and C-terminal portions of VP1 antigen. High-titred human neutralizing antibodies were significantly more reactive with the N-terminal half of VP1 than weak or negative sera. The N-terminal half of human enterovirus 71 is likely to have important neutralizing antibody determinants and should be investigated further in vaccine development efforts.

Characterization of pharmacologically active compounds that inhibit poliovirus and enterovirus 71 infectivity

“…However, there is no effective therapy for vaccineassociated paralytic poliomyelitis, which is caused by virulent revertants of vaccine strains at a rate of one case per 520 000 doses associated with the first dose of the vaccine (Nkowane et al, 1987). For EV71, various vaccine candidates and therapies are being developed, but no vaccine has been established (Chen et al, 2006;Chiu et al, 2006;Liu et al, 2005Liu et al, , 2007Shih et al, 2004;Tan & Cardosa, 2007;Tung et al, 2007;Wu et al, 2007;Yu et al, 2000). The results obtained in this study would be useful for the identification of novel targets to develop antienterovirus drugs that could serve as therapeutic and/or prophylactic agents against acute neurological diseases caused by enterovirus infection.…”

Cellular kinase inhibitors that suppress enterovirus replication have a conserved target in viral protein 3A similar to that of enviroxime

“…However, there is no effective therapeutic means for vaccine-associated paralytic poliomyelitis caused by virulent revertants of vaccine strains, which occurred at a rate of one case per 520 000 vaccinations with the first dose of the live-attenuated vaccine (Nkowane et al, 1987). For EV71, various vaccine candidates and therapeutic means are being developed, but no vaccine has been established (Arita et al, 2005a(Arita et al, , 2007Chen et al, 2006;Chiu et al, 2006;Liu et al, 2005Liu et al, , 2007 Shih et al, 2004;Tan & Cardosa, 2007;Tung et al, 2007;Wu et al, 2007; Yu et al, 2000).…”

“…However, there is no effective therapeutic means for vaccine-associated paralytic poliomyelitis caused by virulent revertants of vaccine strains, which occurred at a rate of one case per 520 000 vaccinations with the first dose of the live-attenuated vaccine (Nkowane et al, 1987). For EV71, various vaccine candidates and therapeutic means are being developed, but no vaccine has been established (Arita et al, 2005a(Arita et al, , 2007Chen et al, 2006;Chiu et al, 2006;Liu et al, 2005Liu et al, , 2007 Shih et al, 2004;Tan & Cardosa, 2007;Tung et al, 2007;Wu et al, 2007; Yu et al, 2000).To date, several anti-enterovirus compounds that target cellular factors and inhibit various stages of virus replication have been identified. Brefeldin A blocks membrane traffic between the cis-and trans-Golgi compartments by targeting a cellular guanine nucleotide- exchange factor, GBF1, and inhibits the replication of PV, but not encephalomyocarditis virus (EMCV) (Belov et al, 2008;Cuconati et al, 1998;Irurzun et al, 1992;Maynell et al, 1992).…”

Cooperative Effect of the Attenuation Determinants Derived from Poliovirus Sabin 1 Strain Is Essential for Attenuation of Enterovirus 71 in the NOD/SCID Mouse Infection Model

“…This suggests a high neuropathogenicity of EV71 similar to that of poliovirus (PV), which causes poliomyelitis in 0.1 to 1.0% of infected individuals (reviewed in reference 46). Currently, various vaccines and treatments against EV71 infection are being developed (13,15,38,39,61,64,66,72,73).Experimental infection models of EV71 have been established in the monkey and mouse (14,21,22,49,50,71). The advantage of the monkey model is that the monkeys inoculated with clinical isolates of EV71 show neurological disorders similar to those observed in human cases of EV71 infection, including tremor, ataxia, and poliomyelitis-like paralysis; these disorders are critical for the evaluation of the neurovirulence of EV71 strains (3, 5).…”

“…This suggests a high neuropathogenicity of EV71 similar to that of poliovirus (PV), which causes poliomyelitis in 0.1 to 1.0% of infected individuals (reviewed in reference 46). Currently, various vaccines and treatments against EV71 infection are being developed (13,15,38,39,61,64,66,72,73).…”