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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 VP2, NSP4 and NSP5.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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f5: Phylogenetic dendrograms based on the nucleotide sequences of VP2, NSP4 and NSP5.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 third ‘tree-group’ includes the remaining genes, VP2, NSP4 and NSP5. For these genes, the most likely host origin of the strains is either animal or human depending on their country of origin. Figure 5 shows that the G8P[6] strains from Ghana are more closely related to RVAs of animal origin (blue bar) than to typical human RVAs (red bar). The VP2 genes of the Ghanaian strains are divided in two clusters sharing only 85.9% nt similarity with each other and showing high similarity to the VP2 sequences of GH018-08 and GH019-08. For NSP5, the Ghanaian strains belong to genotype H3, clustering together with RVAs isolated from animals such as cow, goat and sheep. For NSP4, the three Ghanaian strains belonged to genotype E2. Both G8P[6] strains are identical and show 90.9% nt similarity to the G8P[1] strain Ghan-059. For all three genes (VP2, NSP4 and NSP5) the strains from Mali and the non-G8 strains from Ghana, formed a monophyletic cluster within the C2, E2 and H2 genotypes, clustering together with typical human RVA strains, isolated in different parts of the world.


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 VP2, NSP4 and NSP5.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

f5: Phylogenetic dendrograms based on the nucleotide sequences of VP2, NSP4 and NSP5.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 third ‘tree-group’ includes the remaining genes, VP2, NSP4 and NSP5. For these genes, the most likely host origin of the strains is either animal or human depending on their country of origin. Figure 5 shows that the G8P[6] strains from Ghana are more closely related to RVAs of animal origin (blue bar) than to typical human RVAs (red bar). The VP2 genes of the Ghanaian strains are divided in two clusters sharing only 85.9% nt similarity with each other and showing high similarity to the VP2 sequences of GH018-08 and GH019-08. For NSP5, the Ghanaian strains belong to genotype H3, clustering together with RVAs isolated from animals such as cow, goat and sheep. For NSP4, the three Ghanaian strains belonged to genotype E2. Both G8P[6] strains are identical and show 90.9% nt similarity to the G8P[1] strain Ghan-059. For all three genes (VP2, NSP4 and NSP5) the strains from Mali and the non-G8 strains from Ghana, formed a monophyletic cluster within the C2, E2 and H2 genotypes, clustering together with typical human RVA strains, isolated in different parts of the world.

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