A Trial Comparing Two Pertussis-containing Vaccines in Pregnancy and Vaccine Responses in UK Mothers and Their Infants

NCT02145624 | Completed Phase 4

• 1 other identifier: iMAP2
• Study Type: interventional
• Target: 366
• Locations: 1 country
• Sites: 3

Brief Summary

Due to an unexpectedly high number of infant deaths from whooping cough in 2012, the Department of Health acted to protect newborns between birth and completion of primary immunisations, the period with greatest risk of disease. Vaccination of pregnant women with whooping cough vaccine in the third trimester of pregnancy was instigated nationally, so that antibodies produced by the Mum would cross the placenta to the unborn child, giving them passive protection at the most vulnerable time. This antibody transfer has been known for some time but has not been compared between the two whooping cough vaccines being used in pregnancy. Any effect the raised antibody might have on infant responses to the vaccines given in the first few months of life has also not been measured. This is particularly important as the infant immunisations include some of the same components as the whooping cough vaccines, which include diphtheria, tetanus and polio. Previous studies have shown that high levels of antibody prior to vaccination may affect subsequent antibody responses. It is therefore important to assess whether administration of the whooping cough vaccine in pregnancy adversely affects the protection afforded by the infant vaccines, particularly to those which are similar, namely tetanus and diphtheria as well as meningitis C and Hib vaccines which include diptheria and tetanus components in their structures. This study will assess immune responses of mothers and their babies (\~200 pairs) to their vaccinations and will allow the comparison of two whooping cough vaccines being used in pregnancy. This will be done by taking small amounts of blood, which is the only way to measure antibody levels (the proxy of the immune response), before and after the vaccinations. A group of unvaccinated women and their babies (50 pairs) will also be recruited to allow comparison of their immune responses.

Conditions

Responses to Infant Immunisations

Keywords

pertussis; maternal vaccination; maternal immunisation; immune response

Outcome Measures

Primary Outcomes (3)

• PT immunogenicity (IgG GMC)

  To compare antiPertussis Toxin (PT) IgG responses following primary immunisation with an acellular pertussiscontaining vaccine in infants born to mothers who received REPEVAX in pregnancy compared to infants whose mothers received BOOSTRIXIPV in pregnancy.

  Birth, 2, 5 and 13 months of age

• Immunogenicity of pertussis antigens (IgG GMC)

  To compare antibody responses to pertussis antigens (concentration of IgG antibody to PT, pertactin (PRN), filamentous haemagglutinnin (FHA) and fimbrial antigens 2 and 3 (FIM 2 and 3\]), tetanus toxoid and diphtheria toxoid at birth amongst infants born to mothers who received REPEVAX in pregnancy compared to infants whose mothers received BOOSTRIXIPV in pregnancy

  Birth, 2, 5 and 13 months of age

• Immunogenicity of infant immunisations - pertussis antigens, meningococcal serogroup C, pnuemococcal vaccines at 2, 5 and 13 months of age, (all IgG GMC and SBA GMT for MenC)

  To compare antibody responses to pertussis antigens \[IgG to PT, PRN, FHA and FIM 2 and 3\], Hib antigen \[PRP\], tetanus toxoid and diphtheria toxoid; meningococcal serogroup C serum bactericidal antibody titres and meningococcal serogroup Cspecific IgG concentrations; 13 serotypespecific pneumococcal IgG concentrations and functional pneumococcal antibody studies at 2, 5 and 13 months of age (just before and one month after primary immunization and one month after booster vaccines) in infants born to mothers who received REPEVAX in pregnancy compared to infants whose mothers received BOOSTRIXIPV in pregnancy and compared to infants whose mothers who did not receive pertussis vaccination in pregnancy

  Birth, 2, 5 and 13 months of age

Other Outcomes (4)

• immunogenicity of pnuemococcal conjugate vaccine

  birth, 2, 5 13 months

• immunogenicity of meningococcal conjugate vaccine

  birth, 2, 5, 13 months

• immunogenicity of diphtheria vaccine

  borth 2, 5, 13 months

Study Arms (3)

Repevax

ACTIVE COMPARATOR

Repevax in pregnancy

Drug: Repevax

Boostrix-IPV

ACTIVE COMPARATOR

Boostrix-IPV in pregnancy

Drug: Boostrix-IPV

unvaccinated

NO INTERVENTION

unvaccinated mothers

Interventions

Repevax DRUG

vaccine

Also known as: Pertussis containing vaccine

Repevax

Boostrix-IPV DRUG

vaccine

Also known as: Pertussis containing vaccine

Boostrix-IPV

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Pregnant women who, at the time of enrolment

You may not qualify if:

• Participants may not be included in the study if any of the following apply:
• All women:
• Bleeding disorder
• Receipt of any pertussis containing vaccine in the previous 12 months
• Women to be vaccinated only (i.e. not the control group):
• Received immunoglobulin or other blood product within the preceding 3 months
• Fulfil any of the contraindications to vaccination specified in The Green Book on Immunisation (https://www.gov.uk/government/organisations/publichealthenglan d/series/immunisationagainstinfectiousdiseasethegreenbook), including:
• A confirmed anaphylactic reaction to a previous dose of diphtheria, tetanus, pertussis or poliomyelitis containing vaccine
• A confirmed anaphylactic reaction to any component of the vaccine
• A confirmed anaphylactic reaction to a previous dose of diphtheria, tetanus, pertussis or poliomyelitis containing vaccine

Sponsors & Collaborators

• Public Health England: lead
• Institute of Child Health: collaborator
• St George's, University of London: collaborator

Study Sites (3)

Gloucestershire

Gloucestershire, Gloucestershire, United Kingdom

Location

Hertfordshire

Hertfordshire, Hertfordshire, United Kingdom

Location

St George's Vaccine Institute

London, United Kingdom

Location

Related Publications (2)

• Grassly NC, Andrews N, Cooper G, Stephens L, Waight P, Jones CE, Heath PT, Calvert A, Southern J, Martin J, Miller E. Effect of maternal immunisation with multivalent vaccines containing inactivated poliovirus vaccine (IPV) on infant IPV immune response: A phase 4, multi-centre randomised trial. Vaccine. 2023 Feb 10;41(7):1299-1302. doi: 10.1016/j.vaccine.2023.01.035. Epub 2023 Jan 21.

  PMID: 36690561 DERIVED

• Jones CE, Calvert A, Southern J, Matheson M, Andrews N, Khalil A, Cuthbertson H, Hallis B, England A, Heath PT, Miller E. A phase IV, multi-centre, randomized clinical trial comparing two pertussis-containing vaccines in pregnant women in England and vaccine responses in their infants. BMC Med. 2021 Jun 8;19(1):138. doi: 10.1186/s12916-021-02005-5.

  PMID: 34098951 DERIVED

Related Links

• PHE website

MeSH Terms

Conditions

Whooping Cough

Condition Hierarchy (Ancestors)

Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Respiratory Tract Diseases

Study Officials

• Elizabeth Coates, PhD

  Public Health England

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 23, 2014
• Study Start: October 1, 2014
• Primary Completion: June 1, 2017
• Study Completion: December 1, 2017
• Last Updated: October 1, 2020

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)