Immunogenicity of a bivalent virus-like particle norovirus vaccine in children from 1 to 8 years of age: A phase 2 randomized, double-blind study

Timo Vesikari; Xavier Saez-Llorens; Vezna Blazevic; Pio Lopez; Eduardo Lopez; Taisei Masuda; Paul M. Mendelman; Mengya Liu; James Sherwood; Frank Baehner; Astrid Borkowski

doi:10.1016/j.vaccine.2022.04.089

Immunogenicity of a bivalent virus-like particle norovirus vaccine in children from 1 to 8 years of age: A phase 2 randomized, double-blind study

Timo Vesikari
, Xavier Saez-Llorens
, Vezna Blazevic
, Pio Lopez
, Eduardo Lopez
, Taisei Masuda
, Paul M. Mendelman
, Mengya Liu
, James Sherwood^*
, Frank Baehner
, Astrid Borkowski

^*Tämän työn vastaava kirjoittaja

Tutkimustuotos: Artikkeli › Tieteellinen › vertaisarvioitu

23 Sitaatiot (Scopus)

75 Lataukset (Pure)

Abstrakti

Background: Young children can suffer severe consequences of norovirus gastroenteritis. We performed a dose-finding study of a bivalent virus-like particle (VLP) vaccine candidate (TAK-214) in healthy 1–8-year-old children. Methods: In this phase 2 study two age cohorts (1–3 and 4–8 years of age inclusive, N = 120 per cohort) of children enrolled from Finland, Panama and Colombia were initially randomized 1:1:1:1 to four groups which were further split into two equal subgroups, to receive one or two intramuscular doses of four TAK-214 formulations containing 15/15, 15/50, 50/50 or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)₃ at 28 days interval. ELISA Pan-Ig and histoblood group antigen-blocking (HBGA) antibodies against each VLP were measured on days 1, 29, 57 and 210. Parents/guardians recorded solicited local and systemic adverse events (AE) and any unsolicited or serious AEs (SAE). Results: All formulations were well-tolerated across both age cohorts and dosage groups with no vaccine-related SAEs reported. Solicited AEs were mostly mild-to-moderate, resolved quickly, and did not increase after the second dose. Pan-Ig and HBGA responses induced after one dose were only slightly increased by the second dose. Across dose groups at Day 29 after one dose GI.1 Pan Ig seroresponse rates (SRR) were 82–97% and 81–96% and GII.4c SRR were 79–97% and 80–91% in 1–3 and 4–8 year-olds, respectively. Respective rates were to 92–93% and 73–92% for GI.1, and 77–100% and 62–83% for GII.4c at Day 57 following two doses. HBGA responses had similar profiles. Both Pan Ig and HBGA geometric mean titers persisted above baseline up to Day 210. Conclusions: All dosages of TAK-214 displayed acceptable reactogenicity in 1–8-year-old children and induced robust, durable immune responses after one dose which are further increased after two doses.

Alkuperäiskieli	Englanti
Sivut	3588-3596
Sivumäärä	9
Julkaisu	Vaccine
Vuosikerta	40
Numero	26
DOI - pysyväislinkit	https://doi.org/10.1016/j.vaccine.2022.04.089
Tila	Julkaistu - 9 kesäk. 2022
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Rahoitus

We are grateful to all the participants and their parents, and to all of the staff at each of the study centers at CEVAXIN Plaza Carolina, Panama, the Centro de Estudios en Infectología Pediátrica S.A.S. Colombia, the University of Tampere Medical School, Finland, and Drs Anitta Ahonen, Tiina Karppa, Aino Forstén, Marita Paassilta, Satu S. Kokko, Tiina Korhonen, Ilkka Seppä and their staff at Järvenpää, Etelä-Helsinki, Pori, Seinäjoki, Itä-Helsinki, Espoo, Oulu, Tampere and Turku sites. We thank Keith Veitch (keithveitch communications, Amsterdam, the Netherlands) for drafting and editorial management of the manuscript funded by Takeda Vaccines GmbH. The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. The investigator(s) adhered to the policies regarding the protection of human subjects as prescribed by Code of Federal Regulations (CFR) Title 45, Volume 1, Part 46; Title 32, Chapter 1, Part 219; and Title 21, Chapter 1, Part 50 (Protection of Human Subjects). The datasets, including the redacted study protocol, redacted statistical analysis plan, and individual participants' data supporting the results reported in this article, will be available three months from an initial request made by researchers who provide a methodologically sound proposal. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protection and requirements for consent and anonymization. This work was supported by the US Army Medical Research and Materiel Command under Contract No. W81XWH-15-C-0063, and by Takeda Vaccines Inc. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: As an institution Takeda Pharmaceuticals International AG reports financial support was provided by US Army Medical Research and Materiel Command. Taisei Masuda, Paul M Mendelman, Mengya Lui, James Sherwood, Frank Baehner, Astrid Borkowski report financial support was provided by Takeda Pharmaceuticals International AG or Takeda Vaccines Inc. TM, PMM, ML, JS, FB and AB were all full-time employees of Takeda Pharmaceuticals International AG or Takeda Vaccines Inc. at the time of the study.

YK:n kestävän kehityksen tavoitteet

Tämä tuotos edistää seuraavia kestävän kehityksen tavoitteita:

SDG 3 – Hyvä terveys ja hyvinvointi

Julkaisufoorumi-taso

Jufo-taso 1

!!ASJC Scopus subject areas

Molecular Medicine
Yleinen immunologia ja mikrobiologia
Yleinen eläinlääketiede
Public Health, Environmental and Occupational Health
Infectious Diseases

Pääsy asiakirjaan

10.1016/j.vaccine.2022.04.089Lisenssi: CC BY

1-s2.0-S0264410X22005503-mainFinal published version, 878 KBLisenssi: CC BY

https://urn.fi/URN:NBN:fi:tuni-202208096303Lisenssi: CC BY

Siteeraa tätä

Vesikari, T., Saez-Llorens, X., Blazevic, V., Lopez, P., Lopez, E., Masuda, T., Mendelman, P. M., Liu, M., Sherwood, J., Baehner, F., & Borkowski, A. (2022). Immunogenicity of a bivalent virus-like particle norovirus vaccine in children from 1 to 8 years of age: A phase 2 randomized, double-blind study. Vaccine, 40(26), 3588-3596. https://doi.org/10.1016/j.vaccine.2022.04.089

@article{b104fafcc47f4550aea2a4568f45749c,

title = "Immunogenicity of a bivalent virus-like particle norovirus vaccine in children from 1 to 8 years of age: A phase 2 randomized, double-blind study",

abstract = "Background: Young children can suffer severe consequences of norovirus gastroenteritis. We performed a dose-finding study of a bivalent virus-like particle (VLP) vaccine candidate (TAK-214) in healthy 1–8-year-old children. Methods: In this phase 2 study two age cohorts (1–3 and 4–8 years of age inclusive, N = 120 per cohort) of children enrolled from Finland, Panama and Colombia were initially randomized 1:1:1:1 to four groups which were further split into two equal subgroups, to receive one or two intramuscular doses of four TAK-214 formulations containing 15/15, 15/50, 50/50 or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3 at 28 days interval. ELISA Pan-Ig and histoblood group antigen-blocking (HBGA) antibodies against each VLP were measured on days 1, 29, 57 and 210. Parents/guardians recorded solicited local and systemic adverse events (AE) and any unsolicited or serious AEs (SAE). Results: All formulations were well-tolerated across both age cohorts and dosage groups with no vaccine-related SAEs reported. Solicited AEs were mostly mild-to-moderate, resolved quickly, and did not increase after the second dose. Pan-Ig and HBGA responses induced after one dose were only slightly increased by the second dose. Across dose groups at Day 29 after one dose GI.1 Pan Ig seroresponse rates (SRR) were 82–97\% and 81–96\% and GII.4c SRR were 79–97\% and 80–91\% in 1–3 and 4–8 year-olds, respectively. Respective rates were to 92–93\% and 73–92\% for GI.1, and 77–100\% and 62–83\% for GII.4c at Day 57 following two doses. HBGA responses had similar profiles. Both Pan Ig and HBGA geometric mean titers persisted above baseline up to Day 210. Conclusions: All dosages of TAK-214 displayed acceptable reactogenicity in 1–8-year-old children and induced robust, durable immune responses after one dose which are further increased after two doses.",

keywords = "Children, Immunogenicity, Norovirus, Reactogenicity, Vaccine",

author = "Timo Vesikari and Xavier Saez-Llorens and Vezna Blazevic and Pio Lopez and Eduardo Lopez and Taisei Masuda and Mendelman, \{Paul M.\} and Mengya Liu and James Sherwood and Frank Baehner and Astrid Borkowski",

note = "Funding Information: We are grateful to all the participants and their parents, and to all of the staff at each of the study centers at CEVAXIN Plaza Carolina, Panama, the Centro de Estudios en Infectolog{\'i}a Pedi{\'a}trica S.A.S. Colombia, the University of Tampere Medical School, Finland, and Drs Anitta Ahonen, Tiina Karppa, Aino Forst{\'e}n, Marita Paassilta, Satu S. Kokko, Tiina Korhonen, Ilkka Sepp{\"a} and their staff at J{\"a}rvenp{\"a}{\"a}, Etel{\"a}-Helsinki, Pori, Sein{\"a}joki, It{\"a}-Helsinki, Espoo, Oulu, Tampere and Turku sites. We thank Keith Veitch (keithveitch communications, Amsterdam, the Netherlands) for drafting and editorial management of the manuscript funded by Takeda Vaccines GmbH. The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. The investigator(s) adhered to the policies regarding the protection of human subjects as prescribed by Code of Federal Regulations (CFR) Title 45, Volume 1, Part 46; Title 32, Chapter 1, Part 219; and Title 21, Chapter 1, Part 50 (Protection of Human Subjects). The datasets, including the redacted study protocol, redacted statistical analysis plan, and individual participants' data supporting the results reported in this article, will be available three months from an initial request made by researchers who provide a methodologically sound proposal. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protection and requirements for consent and anonymization. Funding Information: This work was supported by the US Army Medical Research and Materiel Command under Contract No. W81XWH-15-C-0063, and by Takeda Vaccines Inc. Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: As an institution Takeda Pharmaceuticals International AG reports financial support was provided by US Army Medical Research and Materiel Command. Taisei Masuda, Paul M Mendelman, Mengya Lui, James Sherwood, Frank Baehner, Astrid Borkowski report financial support was provided by Takeda Pharmaceuticals International AG or Takeda Vaccines Inc. TM, PMM, ML, JS, FB and AB were all full-time employees of Takeda Pharmaceuticals International AG or Takeda Vaccines Inc. at the time of the study. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = jun,

day = "9",

doi = "10.1016/j.vaccine.2022.04.089",

language = "English",

volume = "40",

pages = "3588--3596",

journal = "Vaccine",

issn = "0264-410X",

publisher = "Elsevier",

number = "26",

}

Vesikari, T, Saez-Llorens, X, Blazevic, V, Lopez, P, Lopez, E, Masuda, T, Mendelman, PM, Liu, M, Sherwood, J, Baehner, F & Borkowski, A 2022, 'Immunogenicity of a bivalent virus-like particle norovirus vaccine in children from 1 to 8 years of age: A phase 2 randomized, double-blind study', Vaccine, Vuosikerta 40, Nro 26, Sivut 3588-3596. https://doi.org/10.1016/j.vaccine.2022.04.089

TY - JOUR

T1 - Immunogenicity of a bivalent virus-like particle norovirus vaccine in children from 1 to 8 years of age

T2 - A phase 2 randomized, double-blind study

AU - Vesikari, Timo

AU - Saez-Llorens, Xavier

AU - Blazevic, Vezna

AU - Lopez, Pio

AU - Lopez, Eduardo

AU - Masuda, Taisei

AU - Mendelman, Paul M.

AU - Liu, Mengya

AU - Sherwood, James

AU - Baehner, Frank

AU - Borkowski, Astrid

N1 - Funding Information: We are grateful to all the participants and their parents, and to all of the staff at each of the study centers at CEVAXIN Plaza Carolina, Panama, the Centro de Estudios en Infectología Pediátrica S.A.S. Colombia, the University of Tampere Medical School, Finland, and Drs Anitta Ahonen, Tiina Karppa, Aino Forstén, Marita Paassilta, Satu S. Kokko, Tiina Korhonen, Ilkka Seppä and their staff at Järvenpää, Etelä-Helsinki, Pori, Seinäjoki, Itä-Helsinki, Espoo, Oulu, Tampere and Turku sites. We thank Keith Veitch (keithveitch communications, Amsterdam, the Netherlands) for drafting and editorial management of the manuscript funded by Takeda Vaccines GmbH. The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. The investigator(s) adhered to the policies regarding the protection of human subjects as prescribed by Code of Federal Regulations (CFR) Title 45, Volume 1, Part 46; Title 32, Chapter 1, Part 219; and Title 21, Chapter 1, Part 50 (Protection of Human Subjects). The datasets, including the redacted study protocol, redacted statistical analysis plan, and individual participants' data supporting the results reported in this article, will be available three months from an initial request made by researchers who provide a methodologically sound proposal. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protection and requirements for consent and anonymization. Funding Information: This work was supported by the US Army Medical Research and Materiel Command under Contract No. W81XWH-15-C-0063, and by Takeda Vaccines Inc. Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: As an institution Takeda Pharmaceuticals International AG reports financial support was provided by US Army Medical Research and Materiel Command. Taisei Masuda, Paul M Mendelman, Mengya Lui, James Sherwood, Frank Baehner, Astrid Borkowski report financial support was provided by Takeda Pharmaceuticals International AG or Takeda Vaccines Inc. TM, PMM, ML, JS, FB and AB were all full-time employees of Takeda Pharmaceuticals International AG or Takeda Vaccines Inc. at the time of the study. Publisher Copyright: © 2022 The Author(s)

PY - 2022/6/9

Y1 - 2022/6/9

N2 - Background: Young children can suffer severe consequences of norovirus gastroenteritis. We performed a dose-finding study of a bivalent virus-like particle (VLP) vaccine candidate (TAK-214) in healthy 1–8-year-old children. Methods: In this phase 2 study two age cohorts (1–3 and 4–8 years of age inclusive, N = 120 per cohort) of children enrolled from Finland, Panama and Colombia were initially randomized 1:1:1:1 to four groups which were further split into two equal subgroups, to receive one or two intramuscular doses of four TAK-214 formulations containing 15/15, 15/50, 50/50 or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3 at 28 days interval. ELISA Pan-Ig and histoblood group antigen-blocking (HBGA) antibodies against each VLP were measured on days 1, 29, 57 and 210. Parents/guardians recorded solicited local and systemic adverse events (AE) and any unsolicited or serious AEs (SAE). Results: All formulations were well-tolerated across both age cohorts and dosage groups with no vaccine-related SAEs reported. Solicited AEs were mostly mild-to-moderate, resolved quickly, and did not increase after the second dose. Pan-Ig and HBGA responses induced after one dose were only slightly increased by the second dose. Across dose groups at Day 29 after one dose GI.1 Pan Ig seroresponse rates (SRR) were 82–97% and 81–96% and GII.4c SRR were 79–97% and 80–91% in 1–3 and 4–8 year-olds, respectively. Respective rates were to 92–93% and 73–92% for GI.1, and 77–100% and 62–83% for GII.4c at Day 57 following two doses. HBGA responses had similar profiles. Both Pan Ig and HBGA geometric mean titers persisted above baseline up to Day 210. Conclusions: All dosages of TAK-214 displayed acceptable reactogenicity in 1–8-year-old children and induced robust, durable immune responses after one dose which are further increased after two doses.

AB - Background: Young children can suffer severe consequences of norovirus gastroenteritis. We performed a dose-finding study of a bivalent virus-like particle (VLP) vaccine candidate (TAK-214) in healthy 1–8-year-old children. Methods: In this phase 2 study two age cohorts (1–3 and 4–8 years of age inclusive, N = 120 per cohort) of children enrolled from Finland, Panama and Colombia were initially randomized 1:1:1:1 to four groups which were further split into two equal subgroups, to receive one or two intramuscular doses of four TAK-214 formulations containing 15/15, 15/50, 50/50 or 50/150 μg of GI.1/GII.4c genotype VLPs and 0.5 mg Al(OH)3 at 28 days interval. ELISA Pan-Ig and histoblood group antigen-blocking (HBGA) antibodies against each VLP were measured on days 1, 29, 57 and 210. Parents/guardians recorded solicited local and systemic adverse events (AE) and any unsolicited or serious AEs (SAE). Results: All formulations were well-tolerated across both age cohorts and dosage groups with no vaccine-related SAEs reported. Solicited AEs were mostly mild-to-moderate, resolved quickly, and did not increase after the second dose. Pan-Ig and HBGA responses induced after one dose were only slightly increased by the second dose. Across dose groups at Day 29 after one dose GI.1 Pan Ig seroresponse rates (SRR) were 82–97% and 81–96% and GII.4c SRR were 79–97% and 80–91% in 1–3 and 4–8 year-olds, respectively. Respective rates were to 92–93% and 73–92% for GI.1, and 77–100% and 62–83% for GII.4c at Day 57 following two doses. HBGA responses had similar profiles. Both Pan Ig and HBGA geometric mean titers persisted above baseline up to Day 210. Conclusions: All dosages of TAK-214 displayed acceptable reactogenicity in 1–8-year-old children and induced robust, durable immune responses after one dose which are further increased after two doses.

KW - Children

KW - Immunogenicity

KW - Norovirus

KW - Reactogenicity

KW - Vaccine

U2 - 10.1016/j.vaccine.2022.04.089

DO - 10.1016/j.vaccine.2022.04.089

M3 - Article

C2 - 35595661

AN - SCOPUS:85130316756

SN - 0264-410X

VL - 40

SP - 3588

EP - 3596

JO - Vaccine

JF - Vaccine

IS - 26

ER -

Immunogenicity of a bivalent virus-like particle norovirus vaccine in children from 1 to 8 years of age: A phase 2 randomized, double-blind study

Abstrakti

Rahoitus

YK:n kestävän kehityksen tavoitteet

Julkaisufoorumi-taso

!!ASJC Scopus subject areas

Pääsy asiakirjaan

Sormenjälki

Siteeraa tätä