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Characterization of a G1P[8] rotavirus causing an outbreak of gastroenteritis in the Northern Territory, Australia, in the vaccine era.

Donato CM, Cowley D, Snelling TL, Akopov A, Kirkness EF, Kirkwood CD - Emerg Microbes Infect (2014)

Bottom Line: In 2010, a large outbreak of rotavirus gastroenteritis occurred in the Alice Springs region of the Northern Territory, Australia.The outbreak occurred 43 months after the introduction of the G1P[8] rotavirus vaccine Rotarix(®).The outbreak was associated with moderate vaccine coverage and possibly low vaccine take in the population.

View Article: PubMed Central - PubMed

Affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital , Melbourne 3052, Victoria, Australia ; La Trobe University , Bundoora 3086, Victoria, Australia.

ABSTRACT
In 2010, a large outbreak of rotavirus gastroenteritis occurred in the Alice Springs region of the Northern Territory, Australia. The outbreak occurred 43 months after the introduction of the G1P[8] rotavirus vaccine Rotarix(®). Forty-three infants were hospitalized during the outbreak and analysis of fecal samples from each infant revealed a G1P[8] rotavirus strain. The outbreak strain was adapted to cell culture and neutralization assays were performed using VP7 and VP4 neutralizing monoclonal antibodies. The outbreak strain exhibited a distinct neutralization resistance pattern compared to the Rotarix(®) vaccine strain. Whole genome sequencing of the 2010 outbreak virus strain demonstrated numerous amino acid differences compared to the Rotarix(®) vaccine strain in the characterized neutralization epitopes of the VP7 and VP4 proteins. Phylogenetic analysis of the outbreak strain revealed a close genetic relationship to global strains, in particular RVA/Human-wt/BEL/BE0098/2009/G1P[8] and RVA/Human-wt/BEL/BE00038/2008/G1P[8] for numerous genes. The 2010 outbreak strain was likely introduced from a globally circulating population of strains rather than evolving from an endemic Australian strain. The outbreak strain possessed antigenic differences in the VP7 and VP4 proteins compared to the Rotarix(®) vaccine strain. The outbreak was associated with moderate vaccine coverage and possibly low vaccine take in the population.

No MeSH data available.


Related in: MedlinePlus

Alignment of VP7 gene of the prototype G1P[8] strains RV4, D, the 2010 G1P[8] Alice Springs outbreak strain and Rotarix® vaccine strain. Amino acid differences between these strains are shaded. Residues comprising the antigenic regions are defined within in brackets. The sites shown to escape neutralization with monoclonal antibodies include RV4:1 (sites 147 and 148, filled circle), RV4:2 (sites 213, filled square), RV4:3 (site 94, filled triangle) and RV4:5: (sites 147, 148 and other undefined sites, filled right pointing triangle).
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fig2: Alignment of VP7 gene of the prototype G1P[8] strains RV4, D, the 2010 G1P[8] Alice Springs outbreak strain and Rotarix® vaccine strain. Amino acid differences between these strains are shaded. Residues comprising the antigenic regions are defined within in brackets. The sites shown to escape neutralization with monoclonal antibodies include RV4:1 (sites 147 and 148, filled circle), RV4:2 (sites 213, filled square), RV4:3 (site 94, filled triangle) and RV4:5: (sites 147, 148 and other undefined sites, filled right pointing triangle).

Mentions: The VP7 gene of the 2010 outbreak samples possessed 94.2% nt and 95.7% aa identity the VP7 gene of Rotarix®. The amino acid differences between the outbreak strains and Rotarix® were analyzed and mapped to the VP7 trimer (Figure 1), identifying several changes in regions of biological function (Figure 2). Several changes in the VP7 protein were located within antigenic regions, T91N and N94S in antigenic region A and M217T in antigenic region C. An additional change was identified at position K291R previously identified in neutralization escape mutants.27 The N94S change identified in the outbreak virus correlated with the loss of neutralization by N-MAb RV4:3 and RV4 polyclonal sera.27 Similarly, the outbreak virus was resistant to neutralization with RV4:5 when compared to Rotarix®. The N-MAb RV4:5 requires the sequence asparagine-lysine at position 147–148 in antigenic region B for neutralization, plus additional unidentified amino acids.27 Resistance to RV4:5 by strain D correlates with the N147S change in antigenic region B (Figure 2). The outbreak strain is resistant to RV4:5, despite a conserved amino acid sequence in antigenic region B when compared to RV4 and Rotarix®. This suggests that additional surface exposed amino acids, potentially the S123N change, are responsible neutralization resistance.


Characterization of a G1P[8] rotavirus causing an outbreak of gastroenteritis in the Northern Territory, Australia, in the vaccine era.

Donato CM, Cowley D, Snelling TL, Akopov A, Kirkness EF, Kirkwood CD - Emerg Microbes Infect (2014)

Alignment of VP7 gene of the prototype G1P[8] strains RV4, D, the 2010 G1P[8] Alice Springs outbreak strain and Rotarix® vaccine strain. Amino acid differences between these strains are shaded. Residues comprising the antigenic regions are defined within in brackets. The sites shown to escape neutralization with monoclonal antibodies include RV4:1 (sites 147 and 148, filled circle), RV4:2 (sites 213, filled square), RV4:3 (site 94, filled triangle) and RV4:5: (sites 147, 148 and other undefined sites, filled right pointing triangle).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126178&req=5

fig2: Alignment of VP7 gene of the prototype G1P[8] strains RV4, D, the 2010 G1P[8] Alice Springs outbreak strain and Rotarix® vaccine strain. Amino acid differences between these strains are shaded. Residues comprising the antigenic regions are defined within in brackets. The sites shown to escape neutralization with monoclonal antibodies include RV4:1 (sites 147 and 148, filled circle), RV4:2 (sites 213, filled square), RV4:3 (site 94, filled triangle) and RV4:5: (sites 147, 148 and other undefined sites, filled right pointing triangle).
Mentions: The VP7 gene of the 2010 outbreak samples possessed 94.2% nt and 95.7% aa identity the VP7 gene of Rotarix®. The amino acid differences between the outbreak strains and Rotarix® were analyzed and mapped to the VP7 trimer (Figure 1), identifying several changes in regions of biological function (Figure 2). Several changes in the VP7 protein were located within antigenic regions, T91N and N94S in antigenic region A and M217T in antigenic region C. An additional change was identified at position K291R previously identified in neutralization escape mutants.27 The N94S change identified in the outbreak virus correlated with the loss of neutralization by N-MAb RV4:3 and RV4 polyclonal sera.27 Similarly, the outbreak virus was resistant to neutralization with RV4:5 when compared to Rotarix®. The N-MAb RV4:5 requires the sequence asparagine-lysine at position 147–148 in antigenic region B for neutralization, plus additional unidentified amino acids.27 Resistance to RV4:5 by strain D correlates with the N147S change in antigenic region B (Figure 2). The outbreak strain is resistant to RV4:5, despite a conserved amino acid sequence in antigenic region B when compared to RV4 and Rotarix®. This suggests that additional surface exposed amino acids, potentially the S123N change, are responsible neutralization resistance.

Bottom Line: In 2010, a large outbreak of rotavirus gastroenteritis occurred in the Alice Springs region of the Northern Territory, Australia.The outbreak occurred 43 months after the introduction of the G1P[8] rotavirus vaccine Rotarix(®).The outbreak was associated with moderate vaccine coverage and possibly low vaccine take in the population.

View Article: PubMed Central - PubMed

Affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital , Melbourne 3052, Victoria, Australia ; La Trobe University , Bundoora 3086, Victoria, Australia.

ABSTRACT
In 2010, a large outbreak of rotavirus gastroenteritis occurred in the Alice Springs region of the Northern Territory, Australia. The outbreak occurred 43 months after the introduction of the G1P[8] rotavirus vaccine Rotarix(®). Forty-three infants were hospitalized during the outbreak and analysis of fecal samples from each infant revealed a G1P[8] rotavirus strain. The outbreak strain was adapted to cell culture and neutralization assays were performed using VP7 and VP4 neutralizing monoclonal antibodies. The outbreak strain exhibited a distinct neutralization resistance pattern compared to the Rotarix(®) vaccine strain. Whole genome sequencing of the 2010 outbreak virus strain demonstrated numerous amino acid differences compared to the Rotarix(®) vaccine strain in the characterized neutralization epitopes of the VP7 and VP4 proteins. Phylogenetic analysis of the outbreak strain revealed a close genetic relationship to global strains, in particular RVA/Human-wt/BEL/BE0098/2009/G1P[8] and RVA/Human-wt/BEL/BE00038/2008/G1P[8] for numerous genes. The 2010 outbreak strain was likely introduced from a globally circulating population of strains rather than evolving from an endemic Australian strain. The outbreak strain possessed antigenic differences in the VP7 and VP4 proteins compared to the Rotarix(®) vaccine strain. The outbreak was associated with moderate vaccine coverage and possibly low vaccine take in the population.

No MeSH data available.


Related in: MedlinePlus