Influencing the widespread adoption of pneumococcal conjugate vaccines in low and middle income countries

Around one million children in the developing world die from pneumonia every year and there has been an urgent demand for safe and effective vaccines that could prevent these deaths.

The School’s research has been key in the development of such a vaccine, which will save the lives of hundreds of thousands of children ever year.

The first pneumococcal vaccines, based on the capsular polysaccharide, were developed in the 1990s, but they induced a poor immune response among young children. Coupling the capsular polysaccharides to a protein to produce a pneumococcal conjugate vaccine (PCV) overcame this problem.

Trials in the US in the early 1990s showed that the PCV vaccine was effective in the developed world but researchers still needed to prove that it could work in low and middle-income countries. A series of trials between 1994 and 1999, co-ordinated by Professor Sir Brian Greenwood, now professor of clinical tropical medicine at the School, answered this question by demonstrating the safety and immunogenicity of PCVs in African infants for the first time.

However, these trials in The Gambia also showed that while PCVs reduced levels of pneumococci of vaccine serotype, these bacteria were replaced by pneumococci of serotypes not represented in the vaccine. This was the first description of “serotype replacement”, which has compromised the effectiveness of the vaccine in many countries.

Between 2000 and 2004 researchers from the School, including Felicity Cutts and Shabbar Jaffar, undertook a phase 3 PCV trial in The Gambia. More than 17,000 children took part in the trial, receiving either three doses of a nine-valent PCV or a placebo. The study showed that the vaccine reduced invasive pneumococcal disease by 77%, severe pneumonia by 37%, hospital admissions by 15% and mortality by 16%.

Shortly after the vaccine became available, the Gambian Ministry of Health introduced a PCV into its routine childhood immunisation schedule. And in 2007, based on the phase 3 Gambia trial results, WHO recommended that the vaccine be introduced in countries with high child mortality.

The Bill and Melinda Gates Foundation is funding a study looking into the impact on mortality and morbidity of a national PCV immunisation programme in The Gambia which is likely to show that it will save thousands of lives.

A 13-valent vaccine has now been introduced and 51 low and middle income countries, supported by the Global Alliance on Vaccination and Immunisation (GAVI), have either introduced or are planning to introduce this vaccine into their routine vaccination schedules.