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Comparative analysis of pentavalent rotavirus vaccine strains and G8 rotaviruses identified during vaccine trial in Africa.

Heylen E, Zeller M, Ciarlet M, Lawrence J, Steele D, Van Ranst M, Matthijnssens J - Sci Rep (2015)

Bottom Line: RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic backbone in vitro reassorted with human outer capsid genes.Because RotaTeqTM possesses a bovine genetic backbone, the high vaccine efficacy against G8 strains might be partially explained by the fact that all these strains contain a complete or partial bovine-like backbone.Altogether, this study supports the hypothesis that gene segments other than VP7 and VP4 play a role in vaccine-induced immunity.

View Article: PubMed Central - PubMed

Affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Laboratory for Clinical and Epidemiological virology, Rega Institute for Medical Research, Leuven, Belgium.

ABSTRACT
RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic backbone in vitro reassorted with human outer capsid genes. During clinical trials of RotaTeqTM in Sub-Saharan Africa, the vaccine efficacy over a 2-year follow-up was lower against the genotypes contained in the vaccine than against the heterotypic G8P[6] and G8P[1] rotavirus strains of which the former is highly prevalent in Africa. Complete genome analyses of 43 complete rotavirus genomes collected during phase III clinical trials of RotaTeqTM in Sub-Saharan Africa, were conducted to gain insight into the high level of cross-protection afforded by RotaTeqTM against these G8 strains. Phylogenetic analysis revealed the presence of a high number of bovine rotavirus gene segments in these human G8 strains. In addition, we performed an in depth analysis on the individual amino acid level which showed that G8 rotaviruses were more similar to the RotaTeqTM vaccine than non-G8 strains. Because RotaTeqTM possesses a bovine genetic backbone, the high vaccine efficacy against G8 strains might be partially explained by the fact that all these strains contain a complete or partial bovine-like backbone. Altogether, this study supports the hypothesis that gene segments other than VP7 and VP4 play a role in vaccine-induced immunity.

No MeSH data available.


Genomic constellations of the reassortant RVA strains of RV5 and the G8 RVA strains analysed in this study.Gene segments of typical human DS-1-like RVA origin are coloured red, the human P[6] VP4 genotype is coloured yellow, and different shades of blue are used to indicate gene segments of distinct animal (most likely bovine or similar) origin.
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f1: Genomic constellations of the reassortant RVA strains of RV5 and the G8 RVA strains analysed in this study.Gene segments of typical human DS-1-like RVA origin are coloured red, the human P[6] VP4 genotype is coloured yellow, and different shades of blue are used to indicate gene segments of distinct animal (most likely bovine or similar) origin.

Mentions: In 2009, the WHO recommended the global use of two oral RVA vaccines, Rotarix™ (GlaxoSmithKline Biologicals, Rixensart, Belgium) and RotaTeq™ (RV5, Merck, Whitehouse Station, NJ, USA). Rotarix™ contains a monovalent live attenuated human G1P[8] strain, whereas RV5 contains 5 reassortant RVA strains (Fig. 1), all possessing a bovine RVA genetic constellation with a human RVA VP7 (G1-G4) or VP4 (P[8]) gene segment7. The WHO recommended clinical studies in Africa and Asia where disease burden is highest and oral vaccines have been less than optimal8910111213. One of these studies was a double-blind, placebo-controlled Phase III clinical trial of RV5 in Ghana, Mali and Kenya, where a large genotypic diversity of RVA strains circulated within the site communities14. Interestingly, the VE against severe rotavirus gastroenteritis during the 2-year period of the study was numerically lower against RVA strains with the G1-G4 or P[8] genotypes contained in the vaccine (34.0%, 95% CI 11.2–51.2) than against heterotypic G8 RVAs (87.5%, 95% CI 6.5–99.7), although this study was not designed to differentiate relative efficacy against individual genotypes1415. Tapia and colleagues described a high prevalence of G8 RVAs during this clinical trial in Africa: 5% (n = 17), 6% (n = 9) and 23% (n = 22) in Mali, Ghana and Kenya respectively14. The VP7 genotype G8 is a typical bovine RVA genotype, in addition to G6 and G10, which are mainly found in combination with several different P-genotypes (P[1], P[5] and P[11])16. A limited number of G8 rotavirus strains have been described in other animal species such as sheep, vicuña, guanaco, goat and camel17181920. G8 has also been detected in humans, with sporadic detection of G8 outside Africa and significant rates of detection inside Africa212223242526272829303132.


Comparative analysis of pentavalent rotavirus vaccine strains and G8 rotaviruses identified during vaccine trial in Africa.

Heylen E, Zeller M, Ciarlet M, Lawrence J, Steele D, Van Ranst M, Matthijnssens J - Sci Rep (2015)

Genomic constellations of the reassortant RVA strains of RV5 and the G8 RVA strains analysed in this study.Gene segments of typical human DS-1-like RVA origin are coloured red, the human P[6] VP4 genotype is coloured yellow, and different shades of blue are used to indicate gene segments of distinct animal (most likely bovine or similar) origin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4594120&req=5

f1: Genomic constellations of the reassortant RVA strains of RV5 and the G8 RVA strains analysed in this study.Gene segments of typical human DS-1-like RVA origin are coloured red, the human P[6] VP4 genotype is coloured yellow, and different shades of blue are used to indicate gene segments of distinct animal (most likely bovine or similar) origin.
Mentions: In 2009, the WHO recommended the global use of two oral RVA vaccines, Rotarix™ (GlaxoSmithKline Biologicals, Rixensart, Belgium) and RotaTeq™ (RV5, Merck, Whitehouse Station, NJ, USA). Rotarix™ contains a monovalent live attenuated human G1P[8] strain, whereas RV5 contains 5 reassortant RVA strains (Fig. 1), all possessing a bovine RVA genetic constellation with a human RVA VP7 (G1-G4) or VP4 (P[8]) gene segment7. The WHO recommended clinical studies in Africa and Asia where disease burden is highest and oral vaccines have been less than optimal8910111213. One of these studies was a double-blind, placebo-controlled Phase III clinical trial of RV5 in Ghana, Mali and Kenya, where a large genotypic diversity of RVA strains circulated within the site communities14. Interestingly, the VE against severe rotavirus gastroenteritis during the 2-year period of the study was numerically lower against RVA strains with the G1-G4 or P[8] genotypes contained in the vaccine (34.0%, 95% CI 11.2–51.2) than against heterotypic G8 RVAs (87.5%, 95% CI 6.5–99.7), although this study was not designed to differentiate relative efficacy against individual genotypes1415. Tapia and colleagues described a high prevalence of G8 RVAs during this clinical trial in Africa: 5% (n = 17), 6% (n = 9) and 23% (n = 22) in Mali, Ghana and Kenya respectively14. The VP7 genotype G8 is a typical bovine RVA genotype, in addition to G6 and G10, which are mainly found in combination with several different P-genotypes (P[1], P[5] and P[11])16. A limited number of G8 rotavirus strains have been described in other animal species such as sheep, vicuña, guanaco, goat and camel17181920. G8 has also been detected in humans, with sporadic detection of G8 outside Africa and significant rates of detection inside Africa212223242526272829303132.

Bottom Line: RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic backbone in vitro reassorted with human outer capsid genes.Because RotaTeqTM possesses a bovine genetic backbone, the high vaccine efficacy against G8 strains might be partially explained by the fact that all these strains contain a complete or partial bovine-like backbone.Altogether, this study supports the hypothesis that gene segments other than VP7 and VP4 play a role in vaccine-induced immunity.

View Article: PubMed Central - PubMed

Affiliation: KU Leuven - University of Leuven, Department of Microbiology and Immunology, Laboratory for Clinical and Epidemiological virology, Rega Institute for Medical Research, Leuven, Belgium.

ABSTRACT
RotaTeqTM is a pentavalent rotavirus vaccine based on a bovine rotavirus genetic backbone in vitro reassorted with human outer capsid genes. During clinical trials of RotaTeqTM in Sub-Saharan Africa, the vaccine efficacy over a 2-year follow-up was lower against the genotypes contained in the vaccine than against the heterotypic G8P[6] and G8P[1] rotavirus strains of which the former is highly prevalent in Africa. Complete genome analyses of 43 complete rotavirus genomes collected during phase III clinical trials of RotaTeqTM in Sub-Saharan Africa, were conducted to gain insight into the high level of cross-protection afforded by RotaTeqTM against these G8 strains. Phylogenetic analysis revealed the presence of a high number of bovine rotavirus gene segments in these human G8 strains. In addition, we performed an in depth analysis on the individual amino acid level which showed that G8 rotaviruses were more similar to the RotaTeqTM vaccine than non-G8 strains. Because RotaTeqTM possesses a bovine genetic backbone, the high vaccine efficacy against G8 strains might be partially explained by the fact that all these strains contain a complete or partial bovine-like backbone. Altogether, this study supports the hypothesis that gene segments other than VP7 and VP4 play a role in vaccine-induced immunity.

No MeSH data available.