Plain English Summary
Background and study aims
The UK national immunisation schedule is updated regularly as new vaccines are licensed so that the best protection is offered to infants and young children. Currently, in addition to diphtheria, tetanus, pertussis (whooping cough) and polio, infants are also vaccinated against the pneumococcus, Hib and Meningococcal C (MenC) bacteria, which are major causes of serious bacterial infections in early childhood, including meningitis, septicaemia (blood poisoning) and pneumonia. The vaccines against these three bacteria were developed by linking (or conjugating) their outer sugar capsules to a carrier protein, such as inactivated tetanus or diphtheria toxin. Unlike polysaccharide vaccines (which are made of the bacterial sugar capsule only and provide limited, short-term immunity in older children and adults only), conjugated vaccines are able to induce very high antibody levels in infants as young as 2 months old. Currently, all infants in the UK receive the same pneumococcal (Prevenar13) and Hibcontaining (Pediacel) vaccines, but can receive any one of 3 licensed MenC vaccines which contain different conjugate proteins (NeisVacC contains tetanus toxoid, while Menjugate and Meningitec contain inactivated diphtheria toxin), depending on which vaccine stock the GP surgery have acquired from the Department of Health at the time. We have recently found that the immune responses of infants to MenC as well as Hib when measured at 5 months (1 month after completing their infant schedule) depends on the conjugate protein in the MenC vaccine. Because all infants receive a booster dose of both MenC and Hib vaccines at 12 months of age, it is likely that they will all develop adequate long-term protection against these infections. In order to verify this, however, we would like to check the immune responses of infants just before and one month after they receive their 12month booster vaccines.
Who can participate?
The families of infants who have completed their primary immunisations at 2, 3 and 4 months of age, and are due their routine 12month booster vaccinations will be invited to have a blood test just before and around one month after the vaccinations. The infants will all receive the vaccines that they would have received as part of the national immunisation programme. The blood samples are the only way to assess the immune responses to vaccination and, because such responses are age and time specific, it would not possible to conduct the study in any other age group.
Our exclusion criteria are minimal and we aim to recruit a representative population of children and their families from the community so that our findings can be generalised to the rest of the population.
What does the study involve?
This study involves obtaining a blood sample just before and one month after infants receive their routine booster vaccinations at 12 months of age as part of the national immunisation programme.
What are the possible benefits and risks of participating?
As this study only involves blood sampling from infants by highly experienced nurses, we do not anticipate any risks or burdens. All families will be free to withdraw from participation at any time without giving a reason and without this affecting the ongoing care from the GP surgery (any outstanding vaccinations required would be notified to the participant's GP surgery).We will ensure any discomfort from blood sampling will be minimised by ensuring that the blood samples will be collected by specialist research nurses with excellent experience of working with young infants, who will use local anaesthetic cream or spray to numb the skin and various distraction techniques before and during the blood sampling. Infants who are found to have low Hib or MenC antibody levels after their 12month booster will be offered an extra dose of the appropriate vaccine in order to ensure long term protection against these bacteria.
Where is the study run from?
GP Practices (UK)
When is the study starting and how long is it expected to run for?
We hope to begin the study in March 2013 and will include children for about 6 months.
Who is funding the study?
UK Department of Health
Who is the main contact?
Professor Elizabeth Miller
liz.miller@hpa.org.uk
Trial website
Additional identifiers
EudraCT number
2012-005110-18
ClinicalTrials.gov number
Protocol/serial number
HPA Protocol No: 12/05
Study information
Scientific title
A prospective study to evaluate the immune responses of UK infants to their routine 12-month booster vaccines following receipt of different meningococcal capsular group C (MenC) conjugate vaccines as part of their primary immunisation schedule (code: P13BOOST)
Acronym
P13Boost
Study hypothesis
To assess responses to booster doses of conjugated vaccines in UK toddlers who have received the vaccinations in infancy as per the routine UK schedule.
Ethics approval
Brent Ethics Committee (UK), 07 December 2012, ref: 12/LO/1875
Study design
Open label phase 4 non randomised study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
GP practices
Trial type
Prevention
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Responses to vaccinations against Hib, meningococcal serogroup C and 13-valent pneumococcal diseases
Intervention
There is only one treatment group. All participants will receive a single dose of each of three vaccines - Hib/MenC (Menitorix®), PCV13 (Prevenar13®), MMR (Priorix®/MMRvaxpro®)
Intervention type
Drug
Phase
Phase IV
Drug names
Hib/MenC (Menitorix®), PCV13 (Prevenar13®), MMR (Priorix®/MMRvaxpro®)
Primary outcome measure
1. Immunoglobulin G (IgG) geometric mean concentrations (GMCs) with 95% Confidence Intervals (95% CI) for Hib capsular polysaccharide and proportions of infants achieving antibody concentrations of ≥0.15 µg/mL or ≥1.00 µg/mL (putative antibody levels considered to provide short-term and long-term protection against invasive disease, respectively) immediately before and 21-42 days after the routine 12-month vaccinations in infants who received MCC-CRM followed by MCC-TT in infancy and compare with infants who received other MCC vaccine combinations
2. Achieving SBA titres ≥8 (the putative protective anti-body titre) or ≥128 (more discriminatory antibody titre) immediately before and 21-42 days after receiving the 12-month booster vaccines in infants who received MCC-CRM followed by MCC-TT in infancy and compare with infants who received other MCC vaccine combinations.
Secondary outcome measures
1. Immunoglobulin G (IgG) geometric mean concentrations (GMCs) with 95% Confidence Intervals (95% CI) for Hib capsular polysac-charide and proportion achieving antibody concentrations of ≥0.15 µg/mL or ≥1.00 µg/mL immediately before and 21-42 days after receiving the 12-month booster vaccines in four groups of in-fants receiving different MCC vaccine combinations in infancy.
2. Serum bactericidal antibody (SBA) titres with 95% CI for MenC and the proportion achieving SBA titres ≥8 or ≥128 immediately before and 21-42 days after receiving the 12-month booster vac-cines in four groups of infants receiving different MCC vaccine combinations in infancy
3. IgG GMC with 95% CI and proportions achieving antibody concen-trations of ≥ 0.35 µg/ml for each of the 13 pneumococcal serotypes included in Prevenar13® immediately before and 21-42 days after receiving the 12-month booster vaccines Diphtheria, tetanus and pertussis antigens (PT, PRN, FHA and then FIMS) IgG antibody GMCs with 95%CI and proportions of infants achieving antibody levels ≥0.1 IU/ml or ≥1.0 IU/ml ) for diphtheria and tetanus (i) immediately before and (ii) 21-42 days after receiving the 12-month booster vaccines.
Overall trial start date
01/02/2013
Overall trial end date
01/08/2013
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Male or female infants:
1. With written informed consent obtained from the parent or legal guardian of the infant to participate in the study and to allow the infants General Practitioner (GP) to be informed of participation in the study and be contacted, if required, for confirmation of the vaccination
history
2. Who have received all their primary immunisations by the time they are 6 months old, including:
2.1. Two doses of any MenC vaccine, with a 3-8 week interval be-tween the first and second dose, with the vaccine product identified by product name or batch number from either the parent-held Red Book or the GP records
2.2. Who are available for their routine 12-month booster vaccines and both blood tests as described in Study Schedule (Section 6.2)
2.3. Do not fulfill any of the exclusion criteria
Participant type
Patient
Age group
Neonate
Gender
Both
Target number of participants
200 +/- 20%
Participant exclusion criteria
Participant may not be included in the study if any of the following apply:
1. History of invasive Haemophilus influenzae serotype b (Hib), pneumococcal or meningococcal disease
2. Confirmed or suspected immunosuppression or immunodeficiency (including HIV)
3. Receipt of a meningococcal quadrivalent conjugate vaccine prior to the 12-month booster
4. Bleeding disorders and/or prolonged bleeding time
5. Major congenital defects or chronic disease
Recruitment start date
01/02/2013
Recruitment end date
01/08/2013
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Health Protection Agency
London
NW9 5EQ
United Kingdom
Sponsor information
Organisation
Health Protection Agency (UK)
Sponsor details
c/o Dr Elizabeth Coates
Research Governance Coordinator
R&D Office
HPA Porton
Porton Down
Salisbury
SP4 0JG
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Department of Health (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list