A new rotavirus VP6-based foreign epitope presenting vector and immunoreactivity of VP4 epitope chimeric proteins.
The VP6, the group antigenic rotavirus (RV), is highly conserved and the most abundant, constituting about 39% of the viral structure proteins by weight. The high degree of identity (>87%-99%) in the primary amino acid sequences suggests VP6-based vaccines could potentially provide heterotypic protection. Although some efforts have been made toward producing recombinant rotavirus VP6 vaccines, the native VP6 is still unsatisfactory as an optimal vaccine. The major neutralizing antigenic epitopes that exist on VP4 or VP7 are not on the native VP6, and as a vector the native VP6 lacks insertion sites that can be used for insertion of foreign epitopes. In this study, a new foreign epitope presenting system using VP6 as a vector (VP6F) was constructed on the outer surface of the vector six sites that could be used for insertion of the foreign epitopes created. Using this system, three VP6-based VP4 epitope chimeric proteins were constructed. Results showed that these chimeric proteins reacted with anti-VP6 and -VP4 antibodies, and elicited antibodies against VP6 and VP4 in guinea pigs. Antibodies against VP6F or antibodies against the chimeric proteins neutralized RV Wa and SA11 infection in vitro. It is optimistic that the limitation for using the native VP6 as a vaccine candidate or vector will be solved with our proposed approach. It is expected that this VP6-based epitope presenting system and the VP6-based VP4 epitope chimeric proteins will be valuable for and contribute to the development of novel RV vaccines and vaccine vectors.
1 Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Institute of Medical Biology , Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, China .
Yumei
Y
Teng
Bingxin
B
Zhao
Xiaoxia
X
Pan
Yuling
Y
Wen
Yuanding
Y
Chen
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics* / Q000276:immunology*; D019677:Artificial Gene Fusion; D036022:Capsid Proteins / Q000235:genetics* / Q000276:immunology*; D000939:Epitopes / Q000235:genetics* / Q000276:immunology*; D005822:Genetic Vectors; D006168:Guinea Pigs; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012401:Rotavirus / Q000235:genetics; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D022243:Rotavirus Vaccines; C060339:VP4 protein, Rotavirus; C061332:VP6 protein, Rotavirus; D014614:Vaccines, Synthetic