Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy

A randomised, double-blind, placebo-controlled trial

Julie E. Bines, Margaret Danchin, Pamela Jackson, Amanda Handley, Emma Watts, Katherine J Lee, Amanda West, Daniel Cowley, Mee Yew Chen, Graeme L. Barnes, Frances Justice, Jim P. Buttery, John B. Carlin, Ruth F Bishop, Barry Taylor, Carl D. Kirkwood, Karen Boniface, Nada Bogdanovic-Sakran, Dan Pavlic, Will Siero & 7 others Jane Standish, Catherine Barker, Nicola Hough, Jane Columb, Frances McCaffrey, Andria McGhie, David Reith

Research output: Contribution to journalArticleResearchpeer-review

41 Citations (Scopus)

Abstract

Background: Despite the success of rotavirus vaccines, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. A birth dose strategy with a vaccine developed from an asymptomatic neonatal rotavirus strain has the potential to address this challenge and provide protection from severe rotavirus disease from birth. Methods: This phase 2a randomised, double-blind, three-arm, placebo-controlled safety and immunogenicity trial was undertaken at a single centre in New Zealand between Jan 13, 2012, and April 17, 2014. Healthy, full-term (≥36 weeks gestation) babies, who weighed at least 2500 g, and were 0-5 days old at the time of randomisation were randomly assigned (1:1:1; computer-generated; telephone central allocation) according to a concealed block randomisation schedule to oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), to vaccine with the first dose given at about 8 weeks after birth (infant schedule), or to placebo. The primary endpoint was cumulative vaccine take (serum immune response or stool shedding of vaccine virus after any dose) after three doses. The immunogenicity analysis included all randomised participants with available outcome data. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611001212943. Findings: 95 eligible participants were randomised, of whom 89 were included in the primary analysis. A cumulative vaccine take was detected in 27 (90%) of 30 participants in the neonatal schedule group after three doses of RV3-BB vaccine compared with four (13%) of 32 participants in the placebo group (difference in proportions 0·78, 95% CI 0·55-0·88; p<0·0001). 25 (93%) of 27 participants in the infant schedule group had a cumulative vaccine take after three doses compared with eight (25%) of 32 participants in the placebo group (difference in proportions 0·68, 0·44-0·81; p<0·0001). A serum IgA response was detected in 19 (63%) of 30 participants and 20 (74%) of 27 participants, and stool shedding of RV3-BB was detected in 21 (70%) of 30 participants and 21 (78%) of 27 participants in the neonatal and infant schedule groups, respectively. The frequency of solicited and unsolicited adverse events was similar across the treatment groups. RV3-BB vaccine was not associated with an increased frequency of fever or gastrointestinal symptoms compared with placebo. Interpretation: RV3-BB vaccine was immunogenic and well tolerated when given as a three-dose neonatal or infant schedule. A birth dose strategy of RV3-BB vaccine has the potential to improve the effectiveness and implementation of rotavirus vaccines. Funding: Australian National Health and Medical Research Council, the New Zealand Health Research Council, and the Murdoch Childrens Research Institute.

Original languageEnglish
Pages (from-to)1389-1397
Number of pages9
JournalLancet Infectious Diseases
Volume15
Issue number12
DOIs
Publication statusPublished - 1 Dec 2015

Cite this

Bines, Julie E. ; Danchin, Margaret ; Jackson, Pamela ; Handley, Amanda ; Watts, Emma ; Lee, Katherine J ; West, Amanda ; Cowley, Daniel ; Chen, Mee Yew ; Barnes, Graeme L. ; Justice, Frances ; Buttery, Jim P. ; Carlin, John B. ; Bishop, Ruth F ; Taylor, Barry ; Kirkwood, Carl D. ; Boniface, Karen ; Bogdanovic-Sakran, Nada ; Pavlic, Dan ; Siero, Will ; Standish, Jane ; Barker, Catherine ; Hough, Nicola ; Columb, Jane ; McCaffrey, Frances ; McGhie, Andria ; Reith, David. / Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy : A randomised, double-blind, placebo-controlled trial. In: Lancet Infectious Diseases. 2015 ; Vol. 15, No. 12. pp. 1389-1397.
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abstract = "Background: Despite the success of rotavirus vaccines, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. A birth dose strategy with a vaccine developed from an asymptomatic neonatal rotavirus strain has the potential to address this challenge and provide protection from severe rotavirus disease from birth. Methods: This phase 2a randomised, double-blind, three-arm, placebo-controlled safety and immunogenicity trial was undertaken at a single centre in New Zealand between Jan 13, 2012, and April 17, 2014. Healthy, full-term (≥36 weeks gestation) babies, who weighed at least 2500 g, and were 0-5 days old at the time of randomisation were randomly assigned (1:1:1; computer-generated; telephone central allocation) according to a concealed block randomisation schedule to oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), to vaccine with the first dose given at about 8 weeks after birth (infant schedule), or to placebo. The primary endpoint was cumulative vaccine take (serum immune response or stool shedding of vaccine virus after any dose) after three doses. The immunogenicity analysis included all randomised participants with available outcome data. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611001212943. Findings: 95 eligible participants were randomised, of whom 89 were included in the primary analysis. A cumulative vaccine take was detected in 27 (90{\%}) of 30 participants in the neonatal schedule group after three doses of RV3-BB vaccine compared with four (13{\%}) of 32 participants in the placebo group (difference in proportions 0·78, 95{\%} CI 0·55-0·88; p<0·0001). 25 (93{\%}) of 27 participants in the infant schedule group had a cumulative vaccine take after three doses compared with eight (25{\%}) of 32 participants in the placebo group (difference in proportions 0·68, 0·44-0·81; p<0·0001). A serum IgA response was detected in 19 (63{\%}) of 30 participants and 20 (74{\%}) of 27 participants, and stool shedding of RV3-BB was detected in 21 (70{\%}) of 30 participants and 21 (78{\%}) of 27 participants in the neonatal and infant schedule groups, respectively. The frequency of solicited and unsolicited adverse events was similar across the treatment groups. RV3-BB vaccine was not associated with an increased frequency of fever or gastrointestinal symptoms compared with placebo. Interpretation: RV3-BB vaccine was immunogenic and well tolerated when given as a three-dose neonatal or infant schedule. A birth dose strategy of RV3-BB vaccine has the potential to improve the effectiveness and implementation of rotavirus vaccines. Funding: Australian National Health and Medical Research Council, the New Zealand Health Research Council, and the Murdoch Childrens Research Institute.",
author = "Bines, {Julie E.} and Margaret Danchin and Pamela Jackson and Amanda Handley and Emma Watts and Lee, {Katherine J} and Amanda West and Daniel Cowley and Chen, {Mee Yew} and Barnes, {Graeme L.} and Frances Justice and Buttery, {Jim P.} and Carlin, {John B.} and Bishop, {Ruth F} and Barry Taylor and Kirkwood, {Carl D.} and Karen Boniface and Nada Bogdanovic-Sakran and Dan Pavlic and Will Siero and Jane Standish and Catherine Barker and Nicola Hough and Jane Columb and Frances McCaffrey and Andria McGhie and David Reith",
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Bines, JE, Danchin, M, Jackson, P, Handley, A, Watts, E, Lee, KJ, West, A, Cowley, D, Chen, MY, Barnes, GL, Justice, F, Buttery, JP, Carlin, JB, Bishop, RF, Taylor, B, Kirkwood, CD, Boniface, K, Bogdanovic-Sakran, N, Pavlic, D, Siero, W, Standish, J, Barker, C, Hough, N, Columb, J, McCaffrey, F, McGhie, A & Reith, D 2015, 'Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: A randomised, double-blind, placebo-controlled trial', Lancet Infectious Diseases, vol. 15, no. 12, pp. 1389-1397. https://doi.org/10.1016/S1473-3099(15)00227-3

Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy : A randomised, double-blind, placebo-controlled trial. / Bines, Julie E.; Danchin, Margaret; Jackson, Pamela; Handley, Amanda; Watts, Emma; Lee, Katherine J; West, Amanda; Cowley, Daniel; Chen, Mee Yew; Barnes, Graeme L.; Justice, Frances; Buttery, Jim P.; Carlin, John B.; Bishop, Ruth F; Taylor, Barry; Kirkwood, Carl D.; Boniface, Karen; Bogdanovic-Sakran, Nada; Pavlic, Dan; Siero, Will; Standish, Jane; Barker, Catherine; Hough, Nicola; Columb, Jane; McCaffrey, Frances; McGhie, Andria; Reith, David.

In: Lancet Infectious Diseases, Vol. 15, No. 12, 01.12.2015, p. 1389-1397.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy

T2 - A randomised, double-blind, placebo-controlled trial

AU - Bines, Julie E.

AU - Danchin, Margaret

AU - Jackson, Pamela

AU - Handley, Amanda

AU - Watts, Emma

AU - Lee, Katherine J

AU - West, Amanda

AU - Cowley, Daniel

AU - Chen, Mee Yew

AU - Barnes, Graeme L.

AU - Justice, Frances

AU - Buttery, Jim P.

AU - Carlin, John B.

AU - Bishop, Ruth F

AU - Taylor, Barry

AU - Kirkwood, Carl D.

AU - Boniface, Karen

AU - Bogdanovic-Sakran, Nada

AU - Pavlic, Dan

AU - Siero, Will

AU - Standish, Jane

AU - Barker, Catherine

AU - Hough, Nicola

AU - Columb, Jane

AU - McCaffrey, Frances

AU - McGhie, Andria

AU - Reith, David

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Background: Despite the success of rotavirus vaccines, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. A birth dose strategy with a vaccine developed from an asymptomatic neonatal rotavirus strain has the potential to address this challenge and provide protection from severe rotavirus disease from birth. Methods: This phase 2a randomised, double-blind, three-arm, placebo-controlled safety and immunogenicity trial was undertaken at a single centre in New Zealand between Jan 13, 2012, and April 17, 2014. Healthy, full-term (≥36 weeks gestation) babies, who weighed at least 2500 g, and were 0-5 days old at the time of randomisation were randomly assigned (1:1:1; computer-generated; telephone central allocation) according to a concealed block randomisation schedule to oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), to vaccine with the first dose given at about 8 weeks after birth (infant schedule), or to placebo. The primary endpoint was cumulative vaccine take (serum immune response or stool shedding of vaccine virus after any dose) after three doses. The immunogenicity analysis included all randomised participants with available outcome data. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611001212943. Findings: 95 eligible participants were randomised, of whom 89 were included in the primary analysis. A cumulative vaccine take was detected in 27 (90%) of 30 participants in the neonatal schedule group after three doses of RV3-BB vaccine compared with four (13%) of 32 participants in the placebo group (difference in proportions 0·78, 95% CI 0·55-0·88; p<0·0001). 25 (93%) of 27 participants in the infant schedule group had a cumulative vaccine take after three doses compared with eight (25%) of 32 participants in the placebo group (difference in proportions 0·68, 0·44-0·81; p<0·0001). A serum IgA response was detected in 19 (63%) of 30 participants and 20 (74%) of 27 participants, and stool shedding of RV3-BB was detected in 21 (70%) of 30 participants and 21 (78%) of 27 participants in the neonatal and infant schedule groups, respectively. The frequency of solicited and unsolicited adverse events was similar across the treatment groups. RV3-BB vaccine was not associated with an increased frequency of fever or gastrointestinal symptoms compared with placebo. Interpretation: RV3-BB vaccine was immunogenic and well tolerated when given as a three-dose neonatal or infant schedule. A birth dose strategy of RV3-BB vaccine has the potential to improve the effectiveness and implementation of rotavirus vaccines. Funding: Australian National Health and Medical Research Council, the New Zealand Health Research Council, and the Murdoch Childrens Research Institute.

AB - Background: Despite the success of rotavirus vaccines, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. A birth dose strategy with a vaccine developed from an asymptomatic neonatal rotavirus strain has the potential to address this challenge and provide protection from severe rotavirus disease from birth. Methods: This phase 2a randomised, double-blind, three-arm, placebo-controlled safety and immunogenicity trial was undertaken at a single centre in New Zealand between Jan 13, 2012, and April 17, 2014. Healthy, full-term (≥36 weeks gestation) babies, who weighed at least 2500 g, and were 0-5 days old at the time of randomisation were randomly assigned (1:1:1; computer-generated; telephone central allocation) according to a concealed block randomisation schedule to oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), to vaccine with the first dose given at about 8 weeks after birth (infant schedule), or to placebo. The primary endpoint was cumulative vaccine take (serum immune response or stool shedding of vaccine virus after any dose) after three doses. The immunogenicity analysis included all randomised participants with available outcome data. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611001212943. Findings: 95 eligible participants were randomised, of whom 89 were included in the primary analysis. A cumulative vaccine take was detected in 27 (90%) of 30 participants in the neonatal schedule group after three doses of RV3-BB vaccine compared with four (13%) of 32 participants in the placebo group (difference in proportions 0·78, 95% CI 0·55-0·88; p<0·0001). 25 (93%) of 27 participants in the infant schedule group had a cumulative vaccine take after three doses compared with eight (25%) of 32 participants in the placebo group (difference in proportions 0·68, 0·44-0·81; p<0·0001). A serum IgA response was detected in 19 (63%) of 30 participants and 20 (74%) of 27 participants, and stool shedding of RV3-BB was detected in 21 (70%) of 30 participants and 21 (78%) of 27 participants in the neonatal and infant schedule groups, respectively. The frequency of solicited and unsolicited adverse events was similar across the treatment groups. RV3-BB vaccine was not associated with an increased frequency of fever or gastrointestinal symptoms compared with placebo. Interpretation: RV3-BB vaccine was immunogenic and well tolerated when given as a three-dose neonatal or infant schedule. A birth dose strategy of RV3-BB vaccine has the potential to improve the effectiveness and implementation of rotavirus vaccines. Funding: Australian National Health and Medical Research Council, the New Zealand Health Research Council, and the Murdoch Childrens Research Institute.

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U2 - 10.1016/S1473-3099(15)00227-3

DO - 10.1016/S1473-3099(15)00227-3

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SP - 1389

EP - 1397

JO - Lancet Infectious Diseases

JF - Lancet Infectious Diseases

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