Skip to main content
SpringerLink
Log in

Comparative characteristics of the VP7 and VP4 antigenic epitopes of the rotaviruses circulating in Russia (Nizhny Novgorod) and the Rotarix and RotaTeq vaccines

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Two live, attenuated rotavirus A (RVA) vaccines, Rotarix and RotaTeq, have been successfully introduced into national immunization programs worldwide. The parent strains of both vaccines were obtained more than 30 years ago. Nonetheless, only very limited data are available on the molecular similarity of the vaccine strains and their genetic relationships to the wild-type strains circulating within the territory of Russian Federation. In this study, we have determined the nucleotide sequences of the genes encoding the viral proteins VP7 and VP4 (the globular domain VP8*) of vaccine strains and natural isolates of rotaviruses in Nizhny Novgorod, Russia. The VP7 and VP4 proteins contain antigenic sites that are the main targets of neutralizing antibodies. Phylogenetic analysis based on VP4 and VP7 showed that the majority of the natural RVA isolates from Nizhny Novgorod and the vaccine strains belong to different clusters. Four amino acids within the VP7 antigenic sites were common in both the wild-type and vaccine strains. The largest number of amino acid differences was found between the vaccine strain Rotarix and the Nizhny Novgorod G2 strains (19 residues out of 29). From 3 to 5 amino acid differences per strain were identified in the antigenic sites of VP4 (domain VP8*) between wild-type strains and the vaccine RotaTeq, and 6-8 substitutions were found when they were compared with the vaccine strain Rotarix. For the first time, immunodominant T-cell epitopes of VP7 were analyzed, and differences in the sequences between the vaccine and the wild-type strains were found. The accumulation of amino acid substitutions in the VP7 and VP4 antigenic sites may potentially reduce the immune protection of vaccinated children from wild-type strains of rotavirus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Aoki ST, Settembre EC, Trask SD et al (2009) Structure of rotavirus outer-layer protein VP7 bound with a neutralizing Fab. Science 12;324(5933):1444–1447. doi:10.1126/science.1170481

  2. Dormitzer PR, Sun ZY, Wagner G, Harrison SC (2002) The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site. EMBO J 21(5):885–897

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Santos N, Hoshino Y (2005) Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine. Rev Med Virol 15(1):29–56

    Article  PubMed  Google Scholar 

  4. Iturriza-Gomara M, Dallman T, Banyai K et al (2009) Rotavirus surveillance in the Europe, 2005–2008: web-enabled reporting and real-time analysis of genotyping and epidemiological data. J Infect Dis 1(200 Suppl 1):215–221. doi:10.1086/605049

    Article  Google Scholar 

  5. Epifanova NV, Sashina TA, Novikova NA et al (2014) Spectrum of rotavirus genotypes circulating in Nizhny Novgorod, 2005–2012. Predominance of genotype G4P[8]. Med Almanac 2(32):52–57 (published in Russian)

    Google Scholar 

  6. Zhirakovskaia EV, Aksanova RKh, Gorbunova MG et al (2012) Genetic diversity of group A rotavirus isolates found in Western Siberia in 2007–2011. Mol Gen Mikrobiol Virusol 1(4):33–41 (published in Russian)

    Google Scholar 

  7. Ward RL, Bernstein DI (2009) Rotarix: a rotavirus vaccine for the world. Clin Infect Dis 48(2):222-228. doi:10.1086/595702

  8. Ciarlet M, Schodel F (2009) Development of a rotavirus vaccine: clinical safety, immunogenicity, and efficacy of the pentavalent rotavirus vaccine, RotaTeq. Vaccine 27(Suppl 6):72–81. doi:10.1016/j.vaccine.2009.09.107

  9. Matthijnssens J, Joelsson DB, Warakomski DJ et al (2010) Molecular and biological characterization of the 5 human-bovine rotavirus (WC3)-based reassortant strains of the pentavalent rotavirus vaccine, RotaTeq. Virology 403(2):111–127. doi:10.1016/j.virol.2010.04.004

    Article  CAS  PubMed  Google Scholar 

  10. WHO (2009) Meeting of the immunization Strategic Advisory Group of Experts, April 2009—conclusions and recommendations. Wkly Epidemiol Rec 84(23):220–236

  11. Soares-Weiser K, Maclehose H, Bergman H et al (2012) Vaccines for preventing rotavirus diarrhea: vaccine in use. Cochrane Database Syst Rev 11:CD008521. doi:10.1002/14651858.CD008521.pub3

  12. Ward RL (2008) Rotavirus vaccines: how they work or don’t work. Expert Rev Mol Med 12(10):e5. doi:10.1017/S1462399408000574

    Article  Google Scholar 

  13. Ward RL (2009) Mechanisms of protection against rotavirus infection and disease. Pediatr Infect Dis J 28(3 Suppl):57–59. doi:10.1097/INF.0b013e3181967c16

    Article  CAS  Google Scholar 

  14. Hoshino Y, Jones RW, Ross J et al (2004) Rotavirus serotype G9 strains belonging to VP7 gene phylogenetic sequence lineage 1 may be more suitable for serotype G9 vaccine candidates than those belonging to lineage 2 or 3. J Virol 78(14):7795–7802

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Ward RL, McNeal MM, Sander DS et al (1993) Immunodominance of the VP4 neutralization protein of rotavirus in protective natural infections of young children. J Virol 67(1):464–468

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Franco MA, Tin C, Greenberg HB (1997) CD8+ T cells can mediate almost complete short-term and partial long-term immunity to rotavirus in mice. J Virol 71(5):4165–4170

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Jaimes MC, Feng N, Greenberg HB (2005) Characterization of homologous and heterologous RV-specific T-cell responses in infant and adult mice. J Virol 79(8):4568–4579

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Honeyman MC, Stone NL, Falk BA et al (2010) Evidence for molecular mimicry between human T cell epitopes in rotavirus and pancreatic islet autoantigens. J Immunol 184(4):2204–2210. doi:10.4049/jimmunol.0900709

  19. Wei J, Li J, Zhang X et al (2009) A naturally processed epitiope on rotavirus VP7 glycoprotein recognized by HLA-A2.1-restricted cytotoxic CD8+ T cells. Viral Immunol 22(3):189–194. doi:10.1089/vim.2008.0091

    Article  CAS  PubMed  Google Scholar 

  20. Arista S, Giammanco GM, De Grazia S et al (2006) Heterogeneity and temporal dynamics of evolution of G1 human rotaviruses in a settled population. J Virol 80(21):10724–10733. doi:10.1128/JVI.00340-06

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Banyai K, Gentsch JR, Martella V et al (2009) Trends in the epidemiology of human G1P[8] rotaviruses: a Hungarian study. J Infect Dis 200(Suppl 1):222–227. doi:10.1086/605052

  22. McDonald SM, Matthijnssens J, McAllen JK et al (2009) Evolutionary dynamics of human rotaviruses: balancing reassortment with preferred genome constellations. PLoS Pathog 5(10):e1000634. doi:10.1371/journal.ppat.1000634

    Article  PubMed Central  PubMed  Google Scholar 

  23. Gentsch JR, Glass RI, Woods P et al (1992) Identification of group A rotavirus gene 4 types by polymerase chain reaction. J Clin Microbiol 30(6):1365–1373

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Maunula L, von Bonsdorff CH (1998) Short sequences define genetic lineages: phylogenetic analysis of group A rotaviruses based on partial sequences of genome segments 4 and 9. J Gen Virol 79:321–332

    CAS  PubMed  Google Scholar 

  25. Gouvea V, Glass RI, Woods P et al (1990) Polymerase chain reaction amplification and typing of rotavirus nucleic acid from stool specimens. J Clin Microbiol 28(2):276–282

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Tamura K, Peterson D, Peterson N et al (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Pettersen EF, Goddard TD, Huang CC et al (2004) UCSF Chimera-a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605–1612

    Article  CAS  PubMed  Google Scholar 

  28. Mouna BH, Hamida-Rebai MB, Heylen E et al (2013) Sequence and phylogenetic analyses of human rotavirus strains: comparison of VP7 and VP8* antigenic epitopes between Tunisian and vaccine strains before national rotavirus vaccine introduction. Infect Genet Evol 18:132–144. doi:10.1016/j.meegid.2013.05.008

    Article  PubMed  Google Scholar 

  29. Zeller M, Patton JT, Heylen E et al (2011) Genetic analyses reveal differences in the VP7 and VP4 antigenic epitopes between human rotaviruses circulating in Belgium and rotaviruses in Rotarix and RotaTeq. J Clin Microbiol 50(3):966–976. doi:10.1128/JCM.05590-11

    Article  PubMed  Google Scholar 

  30. Coulson BS, Grimwood K, Hudson IL et al (1992) Role of coproantibody in clinical protection of children during reinfection with rotavirus. J Clin Microbiol 30(7):1678–1684

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Franco MA, Angel J, Greenberg HB (2006) Immunity and correlates of protection for rotavirus vaccines. Vaccine 24(15):2718–2731

  32. Offit PA, Coupar BE, Svoboda YM et al (1994) Induction of RV-specific cytotoxic T lymphocytes by vaccinia virus recombinants expressing individual RV genes. Virology 198(1):10–16

    Article  CAS  PubMed  Google Scholar 

  33. Novikova NA, Morozova OV, Epifanova NV et al (2012) Rotavirus infection in children of Nizhny Novgorod, Russia: the gradual change of the virus allele from P[8]-1 to P[8]-3 in the period 1984-2010. Arch Virol 157(12):2405–2409. doi:10.1007/s00705-012-1426-4

    Article  CAS  PubMed  Google Scholar 

  34. Hull JJ, Teel EN, Kerin TK et al (2011) National Rotavirus Strain Surveillance System. United States rotavirus strain surveillance from 2005 to 2008: genotype prevalence before and after vaccine introduction. Pediatr Infect Dis J 30(1 Suppl):42–47. doi:10.1097/INF.0b013e3181fefd78

  35. Kirkwood CD, Boniface K, Barnes GL, Bishop RF (2011) Distribution of rotavirus genotypes after introduction of rotavirus vaccines, Rotarix® and RotaTeq®, into the National Immunization Program of Australia. Pediatr Infect Dis J 30(1 Suppl):48–53. doi:10.1097/INF.0b013e3181fefd90

    Article  Google Scholar 

  36. Pelte C, Cherepnev G, Wang Y et al (2004) Random screening of proteins for HLA-A*0201-binding nine-amino acid peptides is not sufficient for identifying CD8 T cell epitopes recognized in the context of HLA-A*0201. J Immunol 172(11):6783–6789

    Article  CAS  PubMed  Google Scholar 

  37. Zeller M, Rahman M, Heylen E et al (2010) Rotavirus incidence and genotype distribution before and after national rotavirus vaccine introduction in Belgium. Vaccine 28(47):7507–7513. doi:10.1016/j.vaccine.2010.09.004

  38. Ward RL, Clark HF, Offit PA (2010) Influence of potential protective mechanisms on the development of live rotavirus vaccines. J Infect Dis 1(202 Suppl):S72–S79. doi:10.1086/653549

    Article  Google Scholar 

  39. Bernstain DI, Ward RL (2004) Rotaviruses. Textbook of pediatric infectious diseases, 5th edn, vol 2. Saunders, Philadelphia, pp 2110–2133

  40. Feng N, Lawton JA, Gilbert J et al (2002) Inhibition of rotavirus replication by a non-neutralizing, rotavirus VP6-specific IgA mAb. J Clin Invest 109(9):1203–1213

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Corthésy B, Benureau Y, Perrier C et al (2006) Rotavirus anti-VP6 secretory immunoglobulin A contributes to protection via intracellular neutralization but not via immune exclusion. J Virol 80(21):10692–10699

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Sergei Gutnikov of Oxford Progress Ltd (Oxford, UK) for his valuable suggestions on stylistic improvements of the manuscript.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Epidemiology of Viral Infections, I.N. Blokhina Nizhny Novgorod Research Institute of Epidemiology and Microbiology, Nizhny Novgorod, Russia

    O. V. Morozova, T. A. Sashina, S. G. Fomina & N. A. Novikova

  2. Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia

    O. V. Morozova, T. A. Sashina, S. G. Fomina & N. A. Novikova

Authors
  1. O. V. Morozova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. A. Sashina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. G. Fomina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. N. A. Novikova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. V. Morozova.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morozova, O.V., Sashina, T.A., Fomina, S.G. et al. Comparative characteristics of the VP7 and VP4 antigenic epitopes of the rotaviruses circulating in Russia (Nizhny Novgorod) and the Rotarix and RotaTeq vaccines. Arch Virol 160, 1693–1703 (2015). https://doi.org/10.1007/s00705-015-2439-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-015-2439-6

Keywords

Search

Navigation