Duration of protection and density of colonisation following pneumococcal conjugate vaccination with a booster dose
Medical Research Council
London School of Hygiene and Tropical Medicine
Global control of pneumococcal disease is hampered by the cost of PCV. More than 20 countries are projected to 'transition' from GAVI vaccine subsidies in the next 5 years. Continuation of PCV programmes will require substantial increases in country expenditure on PCV. Gambia introduced a three-dose PCV schedule without a booster dose (a '3+0' schedule), with large reductions in vaccine-type (VT) invasive pneumococcal disease (IPD) and pneumonia. Now that VT IPD is controlled, a cluster-randomised trial has begun comparing the ongoing use of the 3+0 schedule with transition to a two-dose schedule with a booster dose at 9 months of age (a '1+1' schedule). Theoretically, the 1+1 schedule will stimulate greater herd protection given its likely greater effect to prevent acquisition of pneumococcal bacteria. The ongoing study measures the effect of the two schedules on acquisition of pneumococcal carriage to 18 months of age as well as immunological measures. Despite this and other studies of the 1+1 schedule that are underway, significant gaps in knowledge remain, and none of the current studies will determine the duration of the effect of the booster dose to prevent acquisition of VT pneumococci, the effect of the booster dose on density of VT colonisation, nor whether anti-pneumococcal IgG concentration or function are associated with rates of VT acquisition. The proposed study will extend randomised follow-up of 784 participants measuring VT acquisition with repeated nasopharyngeal specimens to 28 months of age, VT colonisation density at age 10 months by qPCR and pneumococcal microarray serotyping, and opsonophagocytic activity in additional participants to compare with the effect of IgG concentration on rates of acquisition. Our findings will inform WHO policy on PCV scheduling, allow mechanistic interpretation of the trial results, and provide duration of protection and force-of-infection inputs into mathematical modeling of the booster dose effect.
3.4 Vaccines / Research Grant