The fractional dose PCV trial
Before the introduction of pneumococcal conjugate vaccines in 2000, approximately 1 million children died each year as a result of infection with the bacteria Streptococcus pneumoniae and the resulting diseases, namely, meningitis, sepsis and pneumonia. Most of the deaths were in Africa and Asia. Where the vaccines have been introduced, they have been highly effective and have already reduced disease. However, at USD 10 per child, they are not affordable to most low-income countries without financial support from Gavi, the Vaccine Alliance. In Kenya, a 10-valent PCV has been implemented since 2011. The greater part of the vaccine cost is subsidized by Gavi. However, in 2022 Gavi will begin to reduce its subsidies to Kenya over a 5-year period so that by 2027 Kenya will be paying the whole cost alone. A reduction in the cost of the PCV programme may be necessary for Kenya to keep delivering its PCV programme.
This trial aims to assess whether lower doses of the two currently commercially available pneumococcal conjugate vaccines protect Kenyan infants as well as the full dose schedules. We will compare the immune response and carriage of the pneumococcus in the nose (a surrogate marker for disease) after vaccination with a full, 40% or 20% dose schedule. The results could be used to enable countries unable to afford the full cost of the vaccine, to continue delivering it in the childhood immunisation programme in the absence of Gavi support.
We will enrol a total of 2100 infants at multiple health centres in Kilifi and Mombasa counties, Kenya.
Healthy infants aged 6-8 weeks of age, who have not yet received PCV through the routine immunisation programme are eligible to enrol and will be randomly allocated a schedule of full doses, 40% doses or 20% doses of PCV10 or PCV13 at their first study visit. Infants will be vaccinated twice more with PCV in a three-dose schedule and will need to attend follow-up visits to have blood tests to assess antibody levels and nasopharyngeal swabs to test for pneumococcal bacteria.
There is a small risk that the children in this study who receive the lower dose schedules will be less well protected than those who receive the full dose. However, because the vaccine has been in use for 7 years already in Kenya and will continue to be in use in the routine immunization programme throughout the study, the bacteria is much less common than it was prior to vaccine introduction and the likelihood of developing disease is very low, such that we do not expect to see a case of invasive pneumococcal disease in our study population. As participants in the study, infants will have access to the study medical staff and will be able to present with any illness at an early stage and receive free treatment and/or referral to the sub-district hospital up until the age of 18 months (when the study ends). If, after analyses, the lower doses are found to not give a good enough immune response, all infants in those groups will be given a single booster vaccination with the full dose at the end of the study to ‘top-up’ their immunity.
If the PCVs are effective at lower doses, the whole community may benefit. If lower doses can be administered the cost of the vaccine programme will fall, meaning it may continue to be delivered by the government for longer.
Trial activies will be ongoing between 2019- 2023, including participant enrolment, data collection, analysis and write up.
Investigators : Anthony Scott (Principal Investigator),Katherine Gallagher (Lead Co-Investigator) Ifedayo Adetifa,Ruth Lucinde,Angela Karani, Jimmy Shangala,Daisy Mugo,Elizabeth Gardiner, Mark Otiende,Mainga Hamaluba