Alternative vaccination schedules with pneumococcal polysaccharide/protein conjugate vaccine: immunogenicity of the prime-booster approach among Gambian infants

ISRCTN	ISRCTN50377687
DOI	https://doi.org/10.1186/ISRCTN50377687
Secondary identifying numbers	WHO/RPC033

Submission date: 04/08/2004
Registration date: 22/09/2004
Last edited: 27/09/2007

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Richard Adegbola
Scientific

Medical Research Council Laboratories
Fajara
Banjul
-
Gambia

Email	radegbola@mrc.gm

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Prevention
Scientific title
Study objectives	Following previous encouraging findings from safety and immunogenicity studies using conjugate Pnc and Hib vaccines in the Gambia, we propose to evaluate the safety and immunogenicity of 7-valent Pnc conjugate (4, 6B, 9V 14 18C 19F 23F) manufactured by Wyeth Lederle Vaccine USA, using different vaccination schedules. The aim is to determine whether fewer doses started earlier in life with or without a booster dose of Pnc polysaccharide can induce a protective antibody response throughout infancy and early childhood. 675 young infants, residing in sites where the large efficacy (Pnc) trial is on-going, will be randomly allocated to one of 3 vaccination schedules using the 7-valent conjugate vaccine to assess the magnitude, duration and quality of the antibody- response to 1-2 doses with or without a booster dose in Upper River Division of The Gambia. The impact of this vaccination schedule on carriage of pneumococci will also be determined. The data from this immunogenicity study and the larger on-going efficacy trial could provide important data for an informed policy decision in developing countries. We propose to use 7-valent vaccine since it is licensed and available, but would be guided by WHO as to the suitability and availability of other possible conjugate vaccines. General objectives: Evaluating the safety and antibody response to 1 or 2 doses of 7-valent conjugate pneumococcal (Pnc) vaccine given early in life with a booster dose of polysaccharide, compared with a standard 3-dose regimen. Specific primary objectives: 1. To determine the immunogenicity of a 7-valent Pnc Conjugate vaccine at ages 18 weeks and 9 months, after one, two and three doses of conjugate vaccines 2. To evaluate the secondary immune response (antibody) to Pnc polysaccharide vaccine at age 10 months after one, two or three doses of 7-valent conjugate vaccine Secondary objectives: 1. To evaluate persistence of antibody at age 15 months 2. To evaluate evidence of memory response following Conjugate vaccines using assays of antibody avidity and affinity 3. To determine naso-pharyngeal carriage of vaccine and non-vaccine serotypes at ages 6 weeks, 18 weeks, 10 and 15 months
Ethics approval(s)	Ethics approval received from the Gambia Government/Medical Research Council (MRC) Laboratories Joint Ethics Committee on the 5th October 2004.
Health condition(s) or problem(s) studied	Pneumococcus/vaccines
Intervention	Group 1: Infants here will receive their only dose of a 7-valent pneumococcal conjugate vaccine at 6 weeks of life and a dose of polysaccharide vaccine at 9 months. Group 2: A dose of conjugate vaccine will be offered at 6 and 14 weeks, and a dose of polysaccharide at 9 months. The third group (3) will be recruited and vaccinated at 6, 10 and 14 weeks of life with the study conjugate vaccine and with the polysaccharide vaccine at 9 months.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Pneumococcal polysaccharide/protein conjugate vaccine
Primary outcome measure	1. Immunogenicity of 7-valent pneumococcal conjugate vaccine at ages 18 weeks and 11 months after one, two and three doses of conjugate vaccines, measuring for antibody concentrations greater than or equal to 0.35 ug/ml 2. Secondary immune response (antibody) to pnuemococcal polysaccharide vaccine at age 11 months after one, two or three doses of 7-valent conjugate vaccine (antibody concentrations greater than or equal to 0.35 ug/ml)
Secondary outcome measures	1. Persistence of antibody at age 15 months of age 2. Evidence of memory response following Conjugate vaccines using assays of antibody avidity and affinity 3. Naso-pharyngeal carriage of vaccine and non-vaccine serotypes at ages 18 weeks, 11 and 15 months of age 4. Monitoring for safety and local reaction up to 15 months of age. Two main aspects of the safety surveillance will be analysed: 4.1. Serious Adverse Events (SAE) 4.2. Local and Systemic reactions Antibody concentrations to serotypes covered by the 7-valent conjugate vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) as well as antibody concentration to selected serotypes covered by the polysaccharide vaccine (1, 3, 5 and 12) will be measured.
Overall study start date	01/05/2005
Completion date	01/01/2007

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Not Specified
Target number of participants	675
Key inclusion criteria	Babies will be recruited when they present for first dose of Diphtheria, Pertussis, Tetanus (DPT)-Haemophilus influenzae type b (Hib) vaccine and written informed consent obtained at that time
Key exclusion criteria	1. Babies born to known human immunodeficiency virus (HIV) positive mothers 2. Those with neurological abnormality 3. No parental consent 4. Established pneumococcal disease
Date of first enrolment	01/05/2005
Date of final enrolment	01/01/2007

Locations

Countries of recruitment

Gambia

Study participating centre

Medical Research Council Laboratories

Banjul
-
Gambia

Sponsor information

Medical Research Council Laboratories (The Gambia)
Research council

Fajara
Banjul
-
Gambia

"ROR"	https://ror.org/025wfj672

Funders

Funder type

Research organisation

World Health Organization (WHO)/Department of Immunisation, Vaccines and Biologicals (IVB) (Switzerland)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan