Immunization with recombinant enterovirus 71 viral capsid protein 1 fragment stimulated antibody responses in hamsters

Abstract

Enterovirus 71 (EV71) causes severe neurological diseases resulting in high mortality in young children worldwide. Development of an effective vaccine against EV71 infection is hampered by the lack of appropriate animal models for efficacy testing of candidate vaccines. Previously, we have successfully tested the immunogenicity and protectiveness of a candidate EV71 vaccine, containing recombinant Newcastle disease virus capsids that display an EV71 VP1 fragment (NPt-VP11-100) protein, in a mouse model of EV71 infection. A drawback of this system is its limited window of EV71 susceptibility period, 2 weeks after birth, leading to restricted options in the evaluation of optimal dosing regimens. To address this issue, we have assessed the NPt-VP11-100 candidate vaccine in a hamster system, which offers a 4-week susceptibility period to EV71 infection. Results obtained showed that the NPt-VP11-100 candidate vaccine stimulated excellent humoral immune response in the hamsters. Despite the high level of antibody production, they failed to neutralize EV71 viruses or protect vaccinated hamsters in viral challenge studies. Nevertheless, these findings have contributed towards a better understanding of the NPt-VP11-100 recombinant protein as a candidate vaccine in an alternative animal model system.

A Consistent Orally-Infected Hamster Model for Enterovirus A71 Encephalomyelitis Demonstrates Squamous Lesions in the Paws, Skin and Oral Cavity Reminiscent of Hand-Foot-and-Mouth Disease

“…The reasons are not clear just as the reasons for a much higher incidence of complicated HFMD in children less than 5 years old are also not fully understood [ 7 ] but may due to immune system immaturity, relative availability of viral receptors or other unknown factors. In conclusion, we believe our orally-infected hamster is a good small animal model to further investigate viral pathogenesis, to model person-to-person transmission of EV-A71 infection, and to test the effectiveness of anti-viral drugs and vaccines [ 27 ].…”

“…Although infection by the natural oral route in animal models is desirable, it is rare and consistently successful infections have never been described [ 21 , 22 , 25 , 26 ]. Preliminary observations in a new hamster model used to test the protective efficacy of an EV-A71 candidate vaccine against infection by a mouse-adapted virus (MAV), suggested that it may be useful as an alternative small animal model for EV-A71 infection [ 27 ]. In this study, we report its further characterization as a suitable model for EV-A71 infection that could be consistently infected by the oral route.…”

Therapeutic and prevention strategies against human enterovirus 71 infection

“…Different delivery systems have been tested for their suitability in expressing the VP1 and to stimulate immune response. They include recombinant VP1 protein expressed in Escherichia coli BL21 [157] , recombinant Newcastle disease virus capsid displaying VP1 [171] , and VP1 expressed in yeast Pischia pastoris [172] . All induced high levels of neutralising antibodies.…”

“…In vitro / in vivo Safe to use Low immunogenicity [153,154,[163][164][165][166][167][168][169][170][171][172][173][174][175][176][177][178]…”