Lot-to-lot consistency, safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine: results from a phase III randomized, multicenter study in infants

Nicola P. Klein, Remon Abu-Elyazeed, Matthew Cornish, Michael L. Leonardi, Leonard B. Weiner, Peter E. Silas, Stanley E. Grogg, Meera Varman, Robert W. Frenck, Brigitte Cheuvart, Yaela Baine, Jacqueline M. Miller, Maarten Leyssen, Narcisa Mesaros, Sumita Roy-Ghanta

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background Vaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination. Methods This phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6 months (primary vaccination) and 15–18 months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31 days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study. Results Of 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines’ antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1 µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5–96.7% and 99.6–100% of participants achieved anti-PRP levels ≥0.15 µg/mL, while 78.3–89.8% and 97.9–99.1% had anti-PRP levels ≥1 µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6%), 24/520 (4.6%), and 21/520 (4.0%) children post-primary vaccination, and 29/2337 (1.2%), 4/435 (0.9%), and 2/400 (0.5%) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1%) SAEs in the Hib-TT groups were considered vaccine-related. Conclusion Hib-TT induced seroprotective antibody concentrations in the majority of participants and was well-tolerated when co-administered with routine pediatric vaccines according to a 3 + 1 schedule.

Original languageEnglish (US)
Pages (from-to)3564-3574
Number of pages11
JournalVaccine
Volume35
Issue number28
DOIs
StatePublished - Jun 16 2017

Fingerprint

Haemophilus influenzae type b
Haemophilus influenzae
Conjugate Vaccines
Multicenter Studies
immune response
vaccines
Safety
Vaccination
Vaccines
vaccination
Pediatrics
Haemophilus Vaccines
Immunization Schedule
Tetanus Toxoid
toxoids

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Lot-to-lot consistency, safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine : results from a phase III randomized, multicenter study in infants. / Klein, Nicola P.; Abu-Elyazeed, Remon; Cornish, Matthew; Leonardi, Michael L.; Weiner, Leonard B.; Silas, Peter E.; Grogg, Stanley E.; Varman, Meera; Frenck, Robert W.; Cheuvart, Brigitte; Baine, Yaela; Miller, Jacqueline M.; Leyssen, Maarten; Mesaros, Narcisa; Roy-Ghanta, Sumita.

In: Vaccine, Vol. 35, No. 28, 16.06.2017, p. 3564-3574.

Research output: Contribution to journalArticle

Klein, NP, Abu-Elyazeed, R, Cornish, M, Leonardi, ML, Weiner, LB, Silas, PE, Grogg, SE, Varman, M, Frenck, RW, Cheuvart, B, Baine, Y, Miller, JM, Leyssen, M, Mesaros, N & Roy-Ghanta, S 2017, 'Lot-to-lot consistency, safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine: results from a phase III randomized, multicenter study in infants', Vaccine, vol. 35, no. 28, pp. 3564-3574. https://doi.org/10.1016/j.vaccine.2017.05.018
Klein, Nicola P. ; Abu-Elyazeed, Remon ; Cornish, Matthew ; Leonardi, Michael L. ; Weiner, Leonard B. ; Silas, Peter E. ; Grogg, Stanley E. ; Varman, Meera ; Frenck, Robert W. ; Cheuvart, Brigitte ; Baine, Yaela ; Miller, Jacqueline M. ; Leyssen, Maarten ; Mesaros, Narcisa ; Roy-Ghanta, Sumita. / Lot-to-lot consistency, safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine : results from a phase III randomized, multicenter study in infants. In: Vaccine. 2017 ; Vol. 35, No. 28. pp. 3564-3574.
@article{c04b1e60a31a4e419644dfde618720dd,
title = "Lot-to-lot consistency, safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine: results from a phase III randomized, multicenter study in infants",
abstract = "Background Vaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination. Methods This phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6 months (primary vaccination) and 15–18 months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31 days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study. Results Of 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines’ antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1 µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5–96.7{\%} and 99.6–100{\%} of participants achieved anti-PRP levels ≥0.15 µg/mL, while 78.3–89.8{\%} and 97.9–99.1{\%} had anti-PRP levels ≥1 µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6{\%}), 24/520 (4.6{\%}), and 21/520 (4.0{\%}) children post-primary vaccination, and 29/2337 (1.2{\%}), 4/435 (0.9{\%}), and 2/400 (0.5{\%}) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1{\%}) SAEs in the Hib-TT groups were considered vaccine-related. Conclusion Hib-TT induced seroprotective antibody concentrations in the majority of participants and was well-tolerated when co-administered with routine pediatric vaccines according to a 3 + 1 schedule.",
author = "Klein, {Nicola P.} and Remon Abu-Elyazeed and Matthew Cornish and Leonardi, {Michael L.} and Weiner, {Leonard B.} and Silas, {Peter E.} and Grogg, {Stanley E.} and Meera Varman and Frenck, {Robert W.} and Brigitte Cheuvart and Yaela Baine and Miller, {Jacqueline M.} and Maarten Leyssen and Narcisa Mesaros and Sumita Roy-Ghanta",
year = "2017",
month = "6",
day = "16",
doi = "10.1016/j.vaccine.2017.05.018",
language = "English (US)",
volume = "35",
pages = "3564--3574",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "28",

}

TY - JOUR

T1 - Lot-to-lot consistency, safety and immunogenicity of 3 lots of Haemophilus influenzae type b conjugate vaccine

T2 - results from a phase III randomized, multicenter study in infants

AU - Klein, Nicola P.

AU - Abu-Elyazeed, Remon

AU - Cornish, Matthew

AU - Leonardi, Michael L.

AU - Weiner, Leonard B.

AU - Silas, Peter E.

AU - Grogg, Stanley E.

AU - Varman, Meera

AU - Frenck, Robert W.

AU - Cheuvart, Brigitte

AU - Baine, Yaela

AU - Miller, Jacqueline M.

AU - Leyssen, Maarten

AU - Mesaros, Narcisa

AU - Roy-Ghanta, Sumita

PY - 2017/6/16

Y1 - 2017/6/16

N2 - Background Vaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination. Methods This phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6 months (primary vaccination) and 15–18 months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31 days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study. Results Of 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines’ antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1 µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5–96.7% and 99.6–100% of participants achieved anti-PRP levels ≥0.15 µg/mL, while 78.3–89.8% and 97.9–99.1% had anti-PRP levels ≥1 µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6%), 24/520 (4.6%), and 21/520 (4.0%) children post-primary vaccination, and 29/2337 (1.2%), 4/435 (0.9%), and 2/400 (0.5%) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1%) SAEs in the Hib-TT groups were considered vaccine-related. Conclusion Hib-TT induced seroprotective antibody concentrations in the majority of participants and was well-tolerated when co-administered with routine pediatric vaccines according to a 3 + 1 schedule.

AB - Background Vaccination against Haemophilus influenzae type b (Hib) is included in routine pediatric immunization schedule in the United States. Previous vaccine shortages have created the need for additional options for Hib vaccination. Methods This phase III, randomized, multi-centered study (NCT01000974) evaluated the safety and immunogenicity of a monovalent tetanus toxoid-conjugate Hib vaccine (Hib-TT) compared to a monovalent (Hib-TT control) and a combination Hib-TT vaccine. We hierarchically assessed lot-to-lot consistency of 3 Hib-TT lots and non-inferiority of Hib-TT to Hib-TT control. We co-administered routine pediatric vaccines with Hib-TT vaccines at 2, 4, 6 months (primary vaccination) and 15–18 months of age (booster vaccination). We recorded adverse events (AEs) for 4 (solicited) and 31 days (unsolicited) post-vaccination and serious AEs (SAEs) throughout the study. Results Of 4009 enrolled children, 3086 completed booster phase. Lot-to-lot consistency was not demonstrated. The study met statistical criteria for non-inferiority of Hib-TT to Hib-TT control in terms of immune responses to Hib and co-administered vaccines’ antigens, but not in terms of participants achieving post-primary vaccination anti-PRP levels ≥1 µg/mL. Because of the hierarchical nature of the objectives, non-inferiority could not be established. In all groups, 92.5–96.7% and 99.6–100% of participants achieved anti-PRP levels ≥0.15 µg/mL, while 78.3–89.8% and 97.9–99.1% had anti-PRP levels ≥1 µg/mL, post-primary and post-booster vaccination, respectively. Immune responses to co-administered vaccines and reported incidence of AEs were comparable among groups. We recorded SAEs for 107/2963 (3.6%), 24/520 (4.6%), and 21/520 (4.0%) children post-primary vaccination, and 29/2337 (1.2%), 4/435 (0.9%), and 2/400 (0.5%) children post-booster vaccination with Hib-TT, Hib-TT control and combination Hib-TT vaccine, respectively; 6/5330 (0.1%) SAEs in the Hib-TT groups were considered vaccine-related. Conclusion Hib-TT induced seroprotective antibody concentrations in the majority of participants and was well-tolerated when co-administered with routine pediatric vaccines according to a 3 + 1 schedule.

UR - http://www.scopus.com/inward/record.url?scp=85019930972&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019930972&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2017.05.018

DO - 10.1016/j.vaccine.2017.05.018

M3 - Article

C2 - 28536030

AN - SCOPUS:85019930972

VL - 35

SP - 3564

EP - 3574

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 28

ER -