Prokaryotic Expression And Comparative Study Of Truncated Human Rotavirus VP4 And The Rotavirus Candidate Recombinant Vaccine P2-VP8

Globally,rotavirus infection is the leading cause of severe diarrhea in infants and young children.Most of the children have been infected by rotavirus before five years old.There was a dramatic decrease in rotavirus related morbidity and mortality with the implementation of rotavirus vaccines.However,the effectiveness of these vaccines in the low-income countries,where rotavirus caused high mortality,were significantly lower than that in developed countries.Thus,it is necessary to develop more effective and safer alternative rotavirus vaccines to decrease rotavirus caused mortality in less developed areas.High titers of maternal antibodies was one reason for the decreased effectiveness of currently available rotavirus vaccines.Non-replicating vaccine,especially recombinant vaccines,was considered as the priority for further development in rotavirus vaccines,because of the safety and potentially higher protective efficacy through parenteral immunization.In our privious studies,the truncated VP4*(aa26-476)of rotavirus LLR was expressed in E.coli and it show good immunogenicity and protective efficacy in mice.In this study,the truncated VP4*of rotavirus Wa,the most prevalent genotypes of rotavirus among infants was expressed and purified.To evaluate the feasibility of Wa-VP4*as a candidate for the development of recombinant rotavirus vaccines,the immunogenicity of VP4*was compared tophase I/II candidate vaccine P2-VP8 in parallel.The results showed that both VP4*and P2-VP8 are homogeneous and thermal stable.In addition,the neutralizing antibody binding activity and immunogenicity of VP4*was higher than that of P2-VP8.Moreover,VP4*also has high immunogenicity and immuno-neutralizing activity in piglet and cynomologous monkeys.Finnally,the serum samples after immunization by VP4*not only neutralize the homologous rotaviruses,but also the heterogenous strains.In conclusion,the recombinant expressed VP4*are highly homogeneous and thermal stable,with higher immunogenicity and neutralizing activity than that of P2-VP8 and high immunogenicity in piglets and cynomologous monkeys,was a more viable candidate than P2-VP8 for further development of recombinant rotavirus vaccines.