Research Of Cross Reaction Caused By Rotaviruses Containing Different Genotypes

Rotavirus (RV) is the predominant cause of severe diarrhea disease in infants and young children worldwide. About 600,000 children die every year from RV, with more than 80% of all RV-related deaths occurring in countries with backward economic and sanitary condition in south Asia and sub-Saharan Africa, which brought different levels of economic burdens and disease burdens to global countries. To date, there have been no specific drugs for treatment of RV infection. The development of RV vaccine is a cost-effective way to prevent and control RV infection.The genomes of RVs are composed of 11 segments of dsRNA, which can code for six structural viral proteins (VP1-VP4 and VP6-VP7) and six nonstructural proteins (NSP1-NSP6). RVs are subdivided into 8 groups (Group A-Group H) according to VP6, of which RVs in Group A are the main cause of young children’s infection. Based on the differences between VP7 (G-type antigen or a glycoprotein) and VP4 (P-type antigen or a protease-sensitive protein), RVs are subdivided into 27 G genotypes (G1-G27) and 35 P genotypes (P[1]-P[35]). The selection of RV vaccine candidates depend on the genotypes of pandemic RVs. Several live attenuated RV vaccines have been used to protect young children against severe RV-induced gastroenteritis, a monovalent human RV vaccine Rotarix (G1P[8] genotype) developed by GlaxoSmithKline Biologicals, a pentavalent human-bovine reassortant RV vaccine RotaTeq (G1, G2, G3, G4, G6 and P[8] genotype) developed by Merck Research Co. and Oral rotavirus (live) vaccine (G10P[12] genotype), a monovalent RV vaccine which were produced by Lanzhou Institute of Biological Products.The preparation and quality control are different between monovalent and multivalent RV vaccine, but the question is whether monovalent RV vaccine can be as effective as multivalent RV vaccine and the current researches are not able to give a definite answer. The convincing efficacy depends on clinical trials, but it is difficult to obtain the data of clinical trials because of the long test period and complicated evaluation system. Therefore, it is important and forward-looking to establish a laboratory evaluation method for the issues above.In this study, we have focused on the comparison between the immunogenicity of monovalent and multivalent RV immunogens to evaluate the differences between the cross-protection caused by monovalent and multivalent RV immunogens. We selected three standard RV strains, Wa (G1P[8]), SA11 (G3P[1]) and Gottfried (G4P[6]) to prepare RV immunogens. The three standard RV strains were treated as the monovalent RV immunogens and the three standard RV stains were mixed into different combinations at various proportions to generate multivalent RV immunogens. Then, ICR mice were immunized with the same total immunogen quantity of monovalent and multivalent RV immunogens. ICR mice were divided into eight groups randomly, three monovalent RV immunogen groups (Group Wa, Group SA11 and Group Gottfried), three bivalent RV immunogen groups (Group Wa+SA11, Group Wa+Gottfried and Group SA11+Gottfried), one trivalent RV immunogen group (Group Wa+SA11+Gottfried) and one control group (Group PBS). After vaccination, serum RV-specific IgG level, serum RV-specific neutralization titers and serum IgA concentration were determined by ELISA test, neutralization test and IgA ELISA Kit respectively to compare and analyze the immunogenicity of monovalent and multivalent RV immunogens.The results revealed that cross neutralizations of serum antibodies that were weaker than homotypic reactions could be caused by monovalent RV immunogens. Cross neutralizations of serum antibodies could be also caused by multivalent RV immunogens. Immune reactions caused by bivalent RV immunogens were stronger than those caused monovalent RV immunogens. Immune reactions caused by trivalent RV immunogens were also stronger than those caused monovalent RV immunogens but weaker than those caused bivalent RV immunogens. Comprehensive analysis suggested that serum RV-specific IgG antibodies, serum RV-specific neutralization antibodies and serum IgA antibodies induced by multivalent RV immunogens were more than those induced by monovalent RV immunogens. Moreover, multivalent RV immunogens could provoke rapider and stronger heterotypic reactions than monovalent RV immunogens. The replacement of multivalent RV vaccine by monovalent RV vaccine is not able to be taken into consideration at present based on the above results.