Improving pneumococcal vaccination strategies to increase immunity in children

The research findings published in the Lancet Infectious Diseases, by UCL researchers based at the Malawi-Liverpool-Wellcome Programme in collaboration with the Malawi Ministry of Health, underline the need for vaccine policy decisions to consider alternative vaccine strategies, including a booster dose, to achieve sustained vaccine-induced antibody levels to control disease.

The bacteria Streptococcus pneumoniae (pneumococcus) is responsible for approximately 300,000 deaths annually worldwide, with a third of these among children younger than five years and with the greatest burden occurring in low-income and middle-income countries (LMICs). 

Pneumonia vaccine programmes

The pneumococcus vaccine (also known as the pneumonia vaccine) protects against serious and potentially fatal pneumococcal infections, including, pneumonia, blood poisoning (sepsis) and meningitis. Pneumococcal conjugate vaccines (PCVs) - currently available for children as either 10-valent (PCV10) or 13-valent (PCV13) vaccines - are used to vaccinate children under two years old and are part of routine infant immunisation programmes across the world. 

Malawi introduced PCV13 in 2011 using a three-dose vaccine schedule, known as a 3+0 schedule. One dose is given at 6, 10, and 14 weeks of age, with no booster given. Despite the high uptake of the vaccine (reported to be around 90%), the 3+0 schedule has not led to sustained population-level antibody immunity beyond the first year of life in Malawi. 

“It is a pattern we see in other countries such as Kenya and The Gambia,” says Dr Todd Swarthout Senior Research Fellow in Epidemiology, UCL and first author of the study. “Vaccine coverage is high, but we see that PCV13 is less effective in reducing the occurrence of pneumococcal diseases in Malawi and other low- and middle-income countries compared to high-income country settings. We wanted to understand why.”   

The research team, under the guidance of Professor Robert Heyderman, Professor of Infectious Diseases at UCL, used sample data from an existing public health study that had been conducted in Malawi between 2016-2018 and modelled the datasets to gauge how immunity could be optimised.

Booster vaccine benefits 

“After the first year of life, we saw post-vaccine antibody concentrations drop below the levels reportedly needed to adequately protect against severe pneumococcal disease. This potentially contributes to persistent carriage, transmission and invasive pneumococcal disease in Malawi and other similar settings,” says Dr Swarthout. “Most African countries have implemented PCV13 using a 3+0 schedule, with no booster dose. This is in stark contrast to most high-income countries providing a booster dose during the child’s second year of life.” 
 
“This work underlines the need for vaccine policy decisions to consider alternative vaccine strategies, including a booster dose, to control pneumococcal disease. Our findings are particularly relevant to researchers working to inform methodologies for evaluating the pending introduction of new pneumococcal conjugate vaccines.”

The same UCL team based at the Malawi-Liverpool-Wellcome Programme is further collaborating with the Malawi Ministry of Health to evaluate the impact of a PCV13 booster dose at 9 months of age (one dose at 6 weeks, 14 weeks and a booster at 9 months of age; known as a 2+1 schedule) to reduce pneumococcus colonization and transmission. This work will be leveraged to also compare the impact of the booster dose on lengthening duration of antibody immunity compared to 3+0 schedule. 
 
Funding support for this study was provided by the Bill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health and Care Research. 

Further information

• Research paper: ‘Waning of antibody levels induced by a 13-valent pneumococcal conjugate vaccine, using a 3 + 0 schedule, within the first year of life among children younger than 5 years in Blantyre, Malawi: an observational, population-level, serosurveillance study.’ Lancet Infectious Diseases. 
• Prof Robert Heyderman academic profile
• Todd Swarthout academic profile
• Malawi-Liverpool-Wellcome Clinical Research Programme
• Bill & Melinda Gates Foundation
• MPRU | NIHR Mucosal Pathogens Research Unit
• Main image: Photo by RF._.studio on Pexels

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