Abstract
Enterovirus 71 (EV71) is responsible for hand, foot and mouth disease with high mortality among children. Various neutralizing B cell epitopes of EV71 have been identified as potential vaccine candidates. Capsid-incorporation of antigens into adenovirus (Ad) has been developed for a novel vaccine approach. We constructed Ad3-based EV71 vaccine vectors by incorporating a neutralizing epitope SP70 containing 15 amino acids derived from capsid protein VP1 of EV71 within the different surface-exposed domains of the capsid protein hexon of Ad3EGFP, a recombinant adenovirus type 3 (Ad3) expressing enhanced green fluorescence protein. Thermostability and growth kinetic assays suggested that the SP70 epitope incorporation into hypervariable region (HVR1, HVR2, or HVR7) of the hexon did not affect Ad fitness. The SP70 epitopes were thought to be exposed on all hexon-modified intact virion surfaces. Repeated administration of BALB/c mice with the modified Ads resulted in boosting of the anti-SP70 humoral immune response. Importantly, the modified Ads immunization of mother mice conferred protection in vivo to neonatal mice against the lethal EV71 challenge, and the modified Ads-immunized mice serum also conferred passive protection against the lethal challenge in newborn mice. Compared with the recombinant GST-fused SP70 protein immunization, immunization with the Ads containing SP70 in HVR1 or HVR2 elicited higher SP70-specific IgG titers, higher neutralization titers, and conferred more effective protection to neonatal mice. Thus, this study provides valuable information for hexon-modified Ad3 vector development as a promising EV71 vaccine candidate and as an epitope-delivering vehicle for other pathogens.
Highlights
Enterovirus 71 (EV71) is the most frequently detected pathogen in hand, foot and mouth disease (HFMD) patients complicated with the severest forms of neurological disorders [1,2,3]
The five loops are located in HVR1, HVR2, HVR4, HVR5, and HVR7 respectively
We found that the SP70 peptide could be genetically inserted into HVR1, HVR2, and HVR7 regions of the adenovirus type 3 (Ad3) hexon without affecting virus formation and virion stability
Summary
Enterovirus 71 (EV71) is the most frequently detected pathogen in hand, foot and mouth disease (HFMD) patients complicated with the severest forms of neurological disorders [1,2,3]. There are no effective antiviral drugs and vaccines presently available. The development of effective vaccines is a top priority in terms of control strategies [8]. EV71 is a small, nonenveloped, positive single-stranded RNA virus with four capsid proteins: VP1, VP2, VP3 and VP4. The neutralizing antibodies elicited by SP70 epitope containing amino acids 208–222 of VP1 protein were able to confer good in vivo passive protection against homologous and heterologous EV71 strains in suckling Balb/c mice [9,10,11]. The epitope-based vaccine represents a promising candidate for EV71
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