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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.


Related in: MedlinePlus

Phylogenetic dendrograms based on the nucleotide sequences of NSP1 and NSP3.Bootstrap values (500 replicates) above 70 are shown. G8 RVA strains analysed in this study are indicated with a triangle (colour code according to Fig. 1), selected non-G8 strains were indicated with a black triangle, viruses present in RV5 are indicated with a diamond.
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f4: Phylogenetic dendrograms based on the nucleotide sequences of NSP1 and NSP3.Bootstrap values (500 replicates) above 70 are shown. G8 RVA strains analysed in this study are indicated with a triangle (colour code according to Fig. 1), selected non-G8 strains were indicated with a black triangle, viruses present in RV5 are indicated with a diamond.

Mentions: The second ‘tree-group’ contains segments NSP1 and NSP3 (Fig. 4). Both the NSP1 and NSP3 genes of all six West-African G8P[6] RVA strains clustered closely to typical human DS-1-like RVAs isolated in countries all over the world, including Belgium (RVA/Human-wt/BEL/BE1498/2009/G3P[6] and RVA/Human-wt/BEL/BE1322/2009/G3P[6]), South-Africa (2371WC), Ghana (GH018-08 and GH019-08), Bangladesh (RVA/Human-wt/BGD/RV161/2000/G12P[6] and RVA/Human-wt/BGD/RV176/2000/G12P[6]), the Democratic Republic of the Congo (RVA/Human-wt/COD/KisB554/2010/G8P[6], RVA/Human-wt/COD/KisB565/2010/G8P[6] and RVA/Human-wt/COD/DRC86/2003/G8P[6]) and Malawi (RVA/Human-wt/MWI/1473/2001/G8P[4]).


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)

Phylogenetic dendrograms based on the nucleotide sequences of NSP1 and NSP3.Bootstrap values (500 replicates) above 70 are shown. G8 RVA strains analysed in this study are indicated with a triangle (colour code according to Fig. 1), selected non-G8 strains were indicated with a black triangle, viruses present in RV5 are indicated with a diamond.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Phylogenetic dendrograms based on the nucleotide sequences of NSP1 and NSP3.Bootstrap values (500 replicates) above 70 are shown. G8 RVA strains analysed in this study are indicated with a triangle (colour code according to Fig. 1), selected non-G8 strains were indicated with a black triangle, viruses present in RV5 are indicated with a diamond.
Mentions: The second ‘tree-group’ contains segments NSP1 and NSP3 (Fig. 4). Both the NSP1 and NSP3 genes of all six West-African G8P[6] RVA strains clustered closely to typical human DS-1-like RVAs isolated in countries all over the world, including Belgium (RVA/Human-wt/BEL/BE1498/2009/G3P[6] and RVA/Human-wt/BEL/BE1322/2009/G3P[6]), South-Africa (2371WC), Ghana (GH018-08 and GH019-08), Bangladesh (RVA/Human-wt/BGD/RV161/2000/G12P[6] and RVA/Human-wt/BGD/RV176/2000/G12P[6]), the Democratic Republic of the Congo (RVA/Human-wt/COD/KisB554/2010/G8P[6], RVA/Human-wt/COD/KisB565/2010/G8P[6] and RVA/Human-wt/COD/DRC86/2003/G8P[6]) and Malawi (RVA/Human-wt/MWI/1473/2001/G8P[4]).

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.


Related in: MedlinePlus