Effect of Tdap upon antibody response to meningococcal polysaccharide when administered before, with or after the quadrivalent meningococcal TT-conjugate vaccine (coadministered with the 13-valent pneumococcal CRM197-conjugate vaccine) in adult Hajj pilgrims: A randomised controlled trial

M Tashani; M Alfelali; O Barasheed; A S Alqahtani; L Heron; M Wong; H Rashid; H Findlow; R Borrow; R Booy

doi:10.1016/j.vaccine.2018.04.033

Effect of Tdap upon antibody response to meningococcal polysaccharide when administered before, with or after the quadrivalent meningococcal TT-conjugate vaccine (coadministered with the 13-valent pneumococcal CRM197-conjugate vaccine) in adult Hajj pilgrims: A randomised controlled trial

Vaccine. 2018 Jul 5;36(29):4375-4382. doi: 10.1016/j.vaccine.2018.04.033. Epub 2018 Jun 5.

Authors

M Tashani¹, M Alfelali², O Barasheed³, A S Alqahtani⁴, L Heron⁵, M Wong⁶, H Rashid⁷, H Findlow⁸, R Borrow⁸, R Booy⁹

Affiliations

¹ The Discipline of Child and Adolescent Health, the Children's Hospital at Westmead Clinical School, The University of Sydney Medical School, Australia; NHMRC Centre for Research Excellence - Immunisation in Understudied and Special Risk Populations: Closing the Gap in Knowledge Through a Multidisciplinary Approach, School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia; National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; Faculty of Medicine, University of Tripoli, Ain Zara, Tripoli, Libya. Electronic address: Mohamed.Tashani@ncahs.health.nsw.gov.au.
² The Discipline of Child and Adolescent Health, the Children's Hospital at Westmead Clinical School, The University of Sydney Medical School, Australia; NHMRC Centre for Research Excellence - Immunisation in Understudied and Special Risk Populations: Closing the Gap in Knowledge Through a Multidisciplinary Approach, School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia; National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; Department of Family and Community Medicine, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia.
³ The Discipline of Child and Adolescent Health, the Children's Hospital at Westmead Clinical School, The University of Sydney Medical School, Australia; NHMRC Centre for Research Excellence - Immunisation in Understudied and Special Risk Populations: Closing the Gap in Knowledge Through a Multidisciplinary Approach, School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia; National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; The Executive Administration of Research, King Abdullah Medical City (KAMC), Makkah, Saudi Arabia.
⁴ National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; School of Public Health, The University of Sydney, Sydney, NSW, Australia.
⁵ National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; Kids Research Institute, The Children's Hospital at Westmead, NSW, Australia.
⁶ Department of Allergy and Immunology, The Children's Hospital at Westmead, Westmead 2145, NSW, Australia.
⁷ The Discipline of Child and Adolescent Health, the Children's Hospital at Westmead Clinical School, The University of Sydney Medical School, Australia; NHMRC Centre for Research Excellence - Immunisation in Understudied and Special Risk Populations: Closing the Gap in Knowledge Through a Multidisciplinary Approach, School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia; National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney, NSW 2145, Australia.
⁸ Vaccine Evaluation Unit, Public Health England, Manchester, Manchester Royal Infirmary, UK.
⁹ The Discipline of Child and Adolescent Health, the Children's Hospital at Westmead Clinical School, The University of Sydney Medical School, Australia; NHMRC Centre for Research Excellence - Immunisation in Understudied and Special Risk Populations: Closing the Gap in Knowledge Through a Multidisciplinary Approach, School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, Australia; National Centre for Immunisation Research and Surveillance (NCIRS), The Children's Hospital at Westmead, NSW, Australia; Marie Bashir Institute for Infectious Diseases and Biosecurity, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney, NSW 2145, Australia; WHO Collaborating Centre for Mass Gatherings and High Consequence/High Visibility Events, Flinders University, Adelaide 5001, Australia.

PMID: 29880243
DOI: 10.1016/j.vaccine.2018.04.033

Abstract

Hajj pilgrims are susceptible to several serious infections and are required to receive multiple vaccinations. Polysaccharide-protein conjugate vaccines contain carrier proteins such as tetanus toxoid (TT), diphtheria toxoid or a mutant of diphtheria toxoid (CRM197). These carrier proteins may interact with other conjugate or combination vaccines containing tetanus or diphtheria on concurrent or sequential administration. We examined the immune interaction of separate and concomitant administration of a tetanus/diphtheria/acellular pertussis (Tdap) vaccine with a TT-conjugated quadrivalent meningococcal vaccine (MCV4) (coadministered with 13-valent pneumococcal CRM197-conjugate vaccine [PCV13]) in adult Australian pilgrims before attending Hajj in 2015. We randomly assigned each participant to one of three vaccination schedules. Group 1 received Tdap 3-4 weeks before receiving MCV4 coadministered with PCV13. Group 2 received all three vaccines concomitantly. Group 3 received MCV4 and PCV13 3-4 weeks before Tdap. Blood samples were collected at baseline, at each vaccination visit and 3-4 weeks after vaccination and tested for response to meningococcal serogroups C, W and Y using a serum bactericidal antibody (rSBA) assay with baby rabbit complement, and to diphtheria and tetanus toxoid, measuring IgG antibodies by ELISA. Participants completed symptom diaries after each vaccination. A total of 166 participants aged 18-64 (median 42) years were recruited, of whom 160 completed the study. Compared to the other groups, Group 1 (given Tdap first) had significantly lower proportion of subjects achieving a ≥4-fold rise in rSBA for serogroup W. No difference was detected across the three groups in achieving protection threshold (rSBA ≥8 post vaccination) or SBA geometric mean titre (GMT) post vaccination. Group 3, which was given MCV4/PCV13 first, had high levels of antibody against diphtheria and tetanus than the other groups, when tested prior to receipt of Tdap; Only the anti-tetanus responses remained significantly higher after Tdap administration. No serious adverse events were reported. In conclusion, when multiple vaccination is required for Hajj pilgrims, administering Tdap concurrently with MCV4/PCV13 produces adequate immune responses, and avoids meningococcal immune interference, in the convenience of a single consultation. However, giving Tdap 3-4 weeks after MCV4/PCV13 has the advantage of an enhanced tetanus toxoid response. The trial is Trials Registry (ANZCTR): ACTRN12613000536763.

Keywords: Carrier interference; Diphtheria and acellular pertussis vaccine; Meningococcal conjugate vaccine; Serum bactericidal antibody.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Animals
Antibodies, Bacterial / blood*
Antibody Formation
Australia
Crowding
Diphtheria-Tetanus-acellular Pertussis Vaccines / administration & dosage*
Female
Humans
Immunization Schedule*
Male
Meningococcal Infections / prevention & control
Meningococcal Vaccines / administration & dosage*
Meningococcal Vaccines / immunology*
Middle Aged
Pneumococcal Vaccines / administration & dosage*
Polysaccharides, Bacterial / immunology*
Religion
Travel-Related Illness
Young Adult

Substances

13-valent pneumococcal vaccine
Antibodies, Bacterial
Diphtheria-Tetanus-acellular Pertussis Vaccines
Meningococcal Vaccines
Pneumococcal Vaccines
Polysaccharides, Bacterial
tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine

Associated data

ANZCTR/ACTRN12613000536763