Immunity to Avirulent Enterovirus 71 and Coxsackie A16 Virus Protects against Enterovirus 71 Infection in Mice

Abstract

In this study, we sought to determine whether intratypic and intertypic cross-reactivity protected against enterovirus 71 (EV71) infection in a murine infection model. We demonstrate that active immunization of 1-day-old mice with avirulent EV71 strain or coxsackie A16 virus (CA16) by the oral route developed anti-EV71 antibodies with neutralizing activity (1:16 and 1:2, respectively). Splenocytes from both EV71-and CA16-immunized mice proliferated upon EV71 or CA16, but not coxsackie B3 virus (CB3), antigen stimulation. Immunized mice became more resistant to virulent EV71 strain challenge than nonimmunized mice. There was an increase in the percentage of activated splenic T cells and B cells in the immunized mice 2 days after EV71 challenge. The CA16 immune serum reacted with EV71 antigens in an enzyme-linked immunosorbent assay and neutralized EV71 but not CB3 or poliovirus at a titer of 1:4. Passive immunization with the CA16 immune serum reduced the clinical score, diminished the organ viral load, and increased the survival rate of mice upon EV71 challenge. CB3 neither shared in vitro cross-reactivity with EV71 nor provided in vivo protection after both active and passive immunization. These results illustrated that live vaccine is feasible for EV71 and that intertypic cross-reactivity of enteroviruses may provide a way to determine the prevalence of EV71.

Tolerability and immunogenicity of an inactivated enterovirus 71 vaccine in Chinese healthy adults and children

“…14,15 Two studies in Taiwan had demonstrated that passive immunization was able to protect against lethal EV71 challenge in new born mice. 1,16 Those results showed that humoral immunity played a key role in protecting against EV71-caused disease. Therefore, it is valid to use neutralizing antibody to reflect the immunogenicity of the study vaccine.…”

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).…”