PATRICK ANSAH PRINCIPAL INVESTIGATOR 22/02/2016

Transcription

1 Evaluation of the Men A specific antibody persistence in Ghanaian children more than five years after immunization with PsA-TT (2.5 μg, 5 μg, or 10 μg polysaccharide concentration) PATRICK ANSAH PRINCIPAL INVESTIGATOR 22/02/2016

2 Study Ra)onale Circula=ng an=bodies are needed for protec=on from acute meningococcal infec=on. Immune persistence studies are essen=al components of the evalua=on of new meningococcal vaccines. Understanding long term immune persistence helps to inform SAGE and MOH on schedules and vaccina=on programme recommenda=ons and decisions. This study will explore the circula=ng bactericidal an=bodies and IgG concentra=ons in infants and toddler who took part in early vaccine trials during MenAfriVac development programme. This study provides a great opportunity to document the longest term dura=on of the immune response to PsA-TT to date for EPI considera=ons 2 2/7/16

3 Alignment of Study with Policy Gaps WHO Recommenda)ons for EPI Introduc)on MenAfriVac5 should be used for rou=ne immuniza=on - infants and young children 3-24 mo A 1-dose schedule, at 9 18 months of age based on local programma=c and epidemiologic considera=ons is preferred. If in a specific context there is a compelling reason to vaccinate infants younger than 9 months, a 2-priming dose infant schedule should be used star=ng at 3 months of age, with doses at least 8 weeks apart. One =me catch-up campaign for birth cohorts born since the ini=al mass vaccina=on and which would not be within the age range targeted by the rou=ne immuniza=on schedule. MenAfriVac10 should be used for catch-up and periodic campaigns from 12 months of age onwards unless bridging studies have been conducted and show that MenAfriVac5 can be used in older age groups. Gaps highlighted in the WHO recommenda)on: The need for a booster dose has not been established MenAfriVac 5 µg response is not known in older children 3 20 FEBRUARY 2015, No. 8, 2015, 90, h7p://

4 Objec)ve and hypothesis Hypothesis One or more doses of Men A vaccine given in early childhood induces long-term (beyond 5 years) sustained levels of meningococcal A an=bodies. Objec=ves To measure meningococcal group A an=body persistence up to and beyond 5 years aaer vaccina=on in infants and toddlers. Addi=onally other assays will be done to characterise the immune persistence of EPI an=gens up to and beyond five years aaer infant vaccina=on. 4 2/7/16

5 Study Design This is a longitudinal observa=onal study with 2 =me point surveys at ~5 and again at ~6 years post the final PsA-TT immuniza=on in children who originally received a completed vaccina=on series of PsA-TT in trial PsA-TT-004. A new comparator arm was included: Children who par=cipated in the MenAfriVac campaign of 2012 Matched in terms of age of vaccina=on (12-18 months) with the group who received a single dose of PsA-TT 10 μg (group 3) This provides evidence of persistence from a real =me sefng, while giving a benchmark for the comparison and interpreta=on of all study groups in light of herd immunity post community campaigns. 5 2/7/16

6 Study Popula)on Study area: Kassena Nankana West District and Kassena Nankana Municipality, Northern Ghana Former subjects from study MVP-PsA-TT-004 who completed their PsA-TT vaccina=on assignment during the study and had their last study visit blood draw at 36 months. A new control group matched in terms of age (12 to 18 months) at =me of vaccine administra=on during the MenAfriVac campaign in 2012 with documenta=on of vaccina=on. 6 2/7/16

7 Past and Current 004 Study Design n (target) Pers-004 study Ghana Mass Campaign occurred Date of last Last over 60 days PER 1 PER 2 study Blood mos. mos. (Oct-Nov) 868 Visit Visit vaccina=on Draw Original study PsA-TT vaccina=on design and age at first vaccina=on Study groups wks. PsA-TT-004 Study Pers-004 Study Design A 2.5μg 2.5μg B 5μg 5μg -- Sep 2011 Poten=al to 175 Mar-10 May have received C 10 µg 10 µg booster during mass campaign μg Blood draw > 5 yrs post final study vaccina=on Blood draw > 6 yrs post final study vaccina=on μg Oct μg mos. New Control 160 Based on defined criteria, 868 subjects from PsA-TT-004 were eligible to par)cipate in persistence study 7

8 Study Endpoints Main endpoint is assessment of immunogenicity. Serum Bactericidal Ac=vity (SBA) A validated assay using baby rabbit complement (rsba) will be used to measure the level (=ter) of func=onal an=body in human sera to Neisseria meningi=dis group A. An=-PsA IgG (ELISA) To measure total IgG levels of an=body (specific IgG concentra=ons) to Neisseria meningi=dis group A capsular polysaccharide. The concentra=on of specific IgG an=bodies in human sera is determined using human standard reference serum pools and appropriate controls Immune responses to various EPI vaccines: measles, diphtheria, pertussis, tetanus, HepB, Hib. Both Men assays are performed by Public Health England, Manchester, UK. 8

9 Current status Visit 1 Sep-Dec 2015 PsA-TT-004 subjects New Control subjects Invited Recruited Could not be located/ Migrated Refusal to par)cipate Deceased Total All Visit 1 samples for primary analysis and EPI tes=ng have been shipped and lab tes=ng is ongoing. Expec=ng results of interim analysis in May

10 Records of Meningi)s vaccines in study subjects Pers-004 Entered Former study subjects At least 1 dose of Campaign MenAfriVac (40.4%)* (of which 213 with a vaccina=on record, remainder oral recollec=on) At least 1 dose of Meningi)s vaccine (other or unspecified received during other reac)ve campaigns) 135 (17.4%) (of which 59 had the campaign dose) No Addi)onal Meningi)s vaccine 386 (49.8%) New control % 15 (9.4%) 145 (90.6%) *Equal distribu=on of campaign dose across previous treatment groups Provides poten=al to assess a MenAfriVac 10 µg booster given > 2 yrs post primary vaccina=on (Primary vaccina=on +/- Booster) 10

11 Data Analysis Assess immune response in subjects who received primary vaccina=on and in those who received primary vaccina=on + campaign dose >2 years later. Assess for differences in immune response >5 yrs based on primary vaccina=on dose and schedule Assessment of an=body levels What is a protec=ve immune threshold? 1:128 rsba 2 mcg IgG If responses are adequate, con=nue with second blood draw yr 2 If subject responses are inadequate consider a Protocol amendment: Provide a MenAfriVac 5µg boost and measure responses pre and 28 days post vaccina=on Provide data to SAGE on older age 5 µg response 11

12 Audience Discussion Assessment of an=body levels What should be considered as the protec=ve immune threshold? 1:128 rsba, 1:8 rsba (lower limit of quan=fica=on)? 2 mcg IgG? > 0.2 mg/ml (lower limit of quan=fica=on)? If subject responses are inadequate should 5 µg vaccina=on be tested (boost)? All or only subset with inadequate response at 5 year =me point? Only test 5 µg (limited subject numbers)? 12

13 PARTNERS/Collaborators Site: Navrongo Health Research Centre, Ghana Study Monitor: FHI360 Data Management: DiagnoSearch Life Sciences Pvt. Ltd External Laboratory: Public Health England Sponsor: Meningi=s Vaccine Sustainability Project (PATH) Advisors: Serum Ins=tute of India (SIIPL) World Health Organiza=on Funder: Bill & Melinda Gates Founda=on 13

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15 Mali Persistence Study (PERS-007) Similar hypothesis as Ghana Study, n=1200 (007), n=160 new age matched control Assess persistence post any circula=ng Men A (campaign in 2010) Dose in study aligns with current plans for a single 5 µg dose in 9-18 mo and campaign dose of 10 µg >1 yr old Allows immune persistence comparison of 5 vs 10 µg in young children over a long period Poten=al to test these children pre and post the catch up campaign being planned in Mali in 2017 (as they would be captured by this campaign) Treatment Groups and Timing Current Alterna=ve Study Design Date of Pers-007 study 9 12 mos mos last Vax 10μg 10μg Sep-13 5μg 5μg Sep-13 10μg -- Dec-12 Mali MenAfriVac campaign 5μg -- Dec-12 1 blood draw (3-4 yrs post vaccina=on) 1 blood draw pre catch up campaign 1 blood draw post catch up campaign 15 01/03/16