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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.


Comparison of the similarity of the G8 strains to RV5 and the non-G8 strains to RV5 per amino acid position.Each amino acid position with a score different from zero was indicated with a dot, color-coded ranging from red (1) to blue (–1). Positive similarity scores represent positions for which G8 strains were more similar to RV5 than non-G8 strains. Negative scores indicate amino acids positions were non-G8 strains are more similar to RV5 strains than G8 strains.
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f7: Comparison of the similarity of the G8 strains to RV5 and the non-G8 strains to RV5 per amino acid position.Each amino acid position with a score different from zero was indicated with a dot, color-coded ranging from red (1) to blue (–1). Positive similarity scores represent positions for which G8 strains were more similar to RV5 than non-G8 strains. Negative scores indicate amino acids positions were non-G8 strains are more similar to RV5 strains than G8 strains.

Mentions: To evaluate if certain individual amino acid positions could contribute to the increased VE of RV5 against G8 strains, we plotted all 5771 amino acids (aa) for which data were available on a scale from –1 to 1, with a score of 1 corresponding to an aa of the G8 strains which was identical to one of those present in RV5, but was not present in the non-G8 DS-1-like RVAs (Fig. 7). In 86.33% of the aa positions the similarity score was 0 (these positions were omitted in Fig. 7), indicating no difference between the G8 and non-G8 strains versus RV5 strains. 7.82% of investigate sites showed a positive score compared to 5.85% with a negative score, indicating that more aa of the G8 RVAs were similar to RV5 than the non-G8 RVAs. Of particular interest were the aa with a score ranging between 0.5 and 1, as these positions in the G8 strains were much more similar to the RV5 strains, compared to the non-G8 RVAs. In total we identified 49 amino acids with a score ranging between 0.57 and 1. Of these, 8 aa were located in VP7, 4 in VP6, 10 in VP1, 21 within VP3, 3 in NSP2 and 3 in NSP5 (Table S3).


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)

Comparison of the similarity of the G8 strains to RV5 and the non-G8 strains to RV5 per amino acid position.Each amino acid position with a score different from zero was indicated with a dot, color-coded ranging from red (1) to blue (–1). Positive similarity scores represent positions for which G8 strains were more similar to RV5 than non-G8 strains. Negative scores indicate amino acids positions were non-G8 strains are more similar to RV5 strains than G8 strains.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Comparison of the similarity of the G8 strains to RV5 and the non-G8 strains to RV5 per amino acid position.Each amino acid position with a score different from zero was indicated with a dot, color-coded ranging from red (1) to blue (–1). Positive similarity scores represent positions for which G8 strains were more similar to RV5 than non-G8 strains. Negative scores indicate amino acids positions were non-G8 strains are more similar to RV5 strains than G8 strains.
Mentions: To evaluate if certain individual amino acid positions could contribute to the increased VE of RV5 against G8 strains, we plotted all 5771 amino acids (aa) for which data were available on a scale from –1 to 1, with a score of 1 corresponding to an aa of the G8 strains which was identical to one of those present in RV5, but was not present in the non-G8 DS-1-like RVAs (Fig. 7). In 86.33% of the aa positions the similarity score was 0 (these positions were omitted in Fig. 7), indicating no difference between the G8 and non-G8 strains versus RV5 strains. 7.82% of investigate sites showed a positive score compared to 5.85% with a negative score, indicating that more aa of the G8 RVAs were similar to RV5 than the non-G8 RVAs. Of particular interest were the aa with a score ranging between 0.5 and 1, as these positions in the G8 strains were much more similar to the RV5 strains, compared to the non-G8 RVAs. In total we identified 49 amino acids with a score ranging between 0.57 and 1. Of these, 8 aa were located in VP7, 4 in VP6, 10 in VP1, 21 within VP3, 3 in NSP2 and 3 in NSP5 (Table S3).

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.