Immunogenicity and safety of two monovalent rotavirus vaccines, ROTAVAC® and ROTAVAC 5D® in Zambian infants.
Immunogenicity
ROTAVAC
ROTAVAC 5D
Rotavirus Vaccine
Safety
Zambia
Journal
Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899
Informations de publication
Date de publication:
16 06 2021
16 06 2021
Historique:
received:
01
10
2020
revised:
17
03
2021
accepted:
28
04
2021
pubmed:
17
5
2021
medline:
9
7
2021
entrez:
16
5
2021
Statut:
ppublish
Résumé
ROTAVAC® (frozen formulation stored at -20 °C) and ROTAVAC 5D® (liquid formulation stable at 2-8 °C) are rotavirus vaccines derived from the 116E human neonatal rotavirus strain, developed and licensed in India. This study evaluated and compared the safety and immunogenicity of these vaccines in an infant population in Zambia. We conducted a phase 2b, open-label, randomized, controlled trial wherein 450 infants 6 to 8 weeks of age were randomized equally to receive three doses of ROTAVAC or ROTAVAC 5D, or two doses of ROTARIX®. Study vaccines were administered concomitantly with routine immunizations. Blood samples were collected pre-vaccination and 28 days after the last dose. Serum anti-rotavirus IgA antibodies were measured by ELISA, with WC3 and 89-12 rotavirus strains as viral lysates in the assays. The primary analysis was to assess non-inferiority of ROTAVAC 5D to ROTAVAC in terms of the geometric mean concentration (GMC) of serum IgA (WC3) antibodies. Seroresponse and seropositivity were also determined. Safety was evaluated as occurrence of immediate, solicited, unsolicited, and serious adverse events after each dose. The study evaluated 388 infants in the per-protocol population. All three vaccines were well tolerated and immunogenic. The post-vaccination GMCs were 14.0 U/mL (95% CI: 10.4, 18.8) and 18.1 U/mL (95% CI: 13.7, 24.0) for the ROTAVAC and ROTAVAC 5D groups, respectively, yielding a ratio of 1.3 (95% CI: 0.9, 1.9), thus meeting the pre-set non-inferiority criteria. Solicited and unsolicited adverse events were similar across all study arms. No death or intussusception case was reported during study period. Among Zambian infants, both ROTAVAC and ROTAVAC 5D were well tolerated and the immunogenicity of ROTAVAC 5D was non-inferior to that of ROTAVAC. These results are consistent with those observed in licensure trials in India and support use of these vaccines across wider geographical areas.
Sections du résumé
BACKGROUND AND AIMS
ROTAVAC® (frozen formulation stored at -20 °C) and ROTAVAC 5D® (liquid formulation stable at 2-8 °C) are rotavirus vaccines derived from the 116E human neonatal rotavirus strain, developed and licensed in India. This study evaluated and compared the safety and immunogenicity of these vaccines in an infant population in Zambia.
METHODS
We conducted a phase 2b, open-label, randomized, controlled trial wherein 450 infants 6 to 8 weeks of age were randomized equally to receive three doses of ROTAVAC or ROTAVAC 5D, or two doses of ROTARIX®. Study vaccines were administered concomitantly with routine immunizations. Blood samples were collected pre-vaccination and 28 days after the last dose. Serum anti-rotavirus IgA antibodies were measured by ELISA, with WC3 and 89-12 rotavirus strains as viral lysates in the assays. The primary analysis was to assess non-inferiority of ROTAVAC 5D to ROTAVAC in terms of the geometric mean concentration (GMC) of serum IgA (WC3) antibodies. Seroresponse and seropositivity were also determined. Safety was evaluated as occurrence of immediate, solicited, unsolicited, and serious adverse events after each dose.
RESULTS
The study evaluated 388 infants in the per-protocol population. All three vaccines were well tolerated and immunogenic. The post-vaccination GMCs were 14.0 U/mL (95% CI: 10.4, 18.8) and 18.1 U/mL (95% CI: 13.7, 24.0) for the ROTAVAC and ROTAVAC 5D groups, respectively, yielding a ratio of 1.3 (95% CI: 0.9, 1.9), thus meeting the pre-set non-inferiority criteria. Solicited and unsolicited adverse events were similar across all study arms. No death or intussusception case was reported during study period.
CONCLUSIONS
Among Zambian infants, both ROTAVAC and ROTAVAC 5D were well tolerated and the immunogenicity of ROTAVAC 5D was non-inferior to that of ROTAVAC. These results are consistent with those observed in licensure trials in India and support use of these vaccines across wider geographical areas.
Identifiants
pubmed: 33992437
pii: S0264-410X(21)00542-9
doi: 10.1016/j.vaccine.2021.04.060
pmc: PMC8204902
pii:
doi:
Substances chimiques
Antibodies, Viral
0
Rotavirus Vaccines
0
Vaccines, Attenuated
0
Types de publication
Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3633-3640Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
J Infect Dis. 2009 Aug 1;200(3):421-9
pubmed: 19545211
Clin Infect Dis. 2016 May 1;62 Suppl 2:S96-S105
pubmed: 27059362
Vaccine. 2019 Jul 18;37(31):4407-4413
pubmed: 31178377
Vaccine. 1998 Feb;16(4):381-7
pubmed: 9607059
Clin Infect Dis. 2016 May 1;62 Suppl 2:S183-7
pubmed: 27059354
Vaccine. 2014 May 23;32(25):3094-100
pubmed: 24704505
JAMA Pediatr. 2018 Oct 1;172(10):958-965
pubmed: 30105384
Lancet. 2014 Jun 21;383(9935):2136-43
pubmed: 24629994
Vaccine. 2019 May 1;37(19):2554-2560
pubmed: 30955982
Stat Med. 1985 Apr-Jun;4(2):213-26
pubmed: 4023479
Vaccine. 2014 Aug 11;32 Suppl 1:A110-6
pubmed: 25091663
Hum Vaccin Immunother. 2018 Jul 3;14(7):1791-1799
pubmed: 29543547
Heliyon. 2017 May 16;3(5):e00302
pubmed: 28560356
Pediatrics. 2016 Feb;137(2):e20152603
pubmed: 26823540
J Infect Dis. 2004 Jun 15;189(12):2290-3
pubmed: 15181577