Altering vaccine doses can save costs, lives

IN 2005, before most low- and middle- income countries started vaccinating children routinely for pneumococcal disease, it caused approximately 1.5 million deaths worldwide annually.

About 700 000 to a million of the deaths were in children under 5 years old. Pneumococcal disease occurs when Streptococcus pneumoniae invades a normally sterile area of the body, causing meningitis, pneumonia, septicaemia or other disease syndromes.

Case fatality rates are high for septicaemia (> 20%) and meningitis (> 50%) in low- and middle- income countries.

Widespread childhood pneumococcal vaccination reduces death and disease – even in unvaccinated individuals. This is because there is less circulation of the bacterium S pneumoniae. The “indirect” immunity is often termed “herd immunity”.

The pneumococcal conjugate vaccine is available in many countries with support from Gavi, the international vaccine support programme.

Gavi has supported 60 low- and middle- income countries to introduce pneumococcal conjugate vaccines into routine vaccination. However, Gavi’s support is focused on the poorest countries.

More than 30 countries, including 11 in Africa, are scheduled to “graduate” out of direct Gavi support when they become wealthy enough.

As countries “graduate” from Gavi support they will need to pay for the pneumococcal conjugate vaccine.

The pneumococcal conjugate vaccine schedule requires three doses. These are usually the most expensive vaccines in childhood immunisation programmes.

South Africa, the only African country that procures the vaccines without financial assistance from Gavi, spends almost half of its vaccine procurement budget on pneumococcal conjugate vaccines.

One strategy to reduce the cost of vaccination is to reduce the number of doses required per child.

We conducted a clinical trial to see if the dosing schedule could be safely reduced while preserving vaccine efficacy, and found that a two- dose schedule induces the same final immune response as a three- dose schedule.

Using a two- dose schedule could reduce vaccine programme costs in low- and middle- income countries. Most low- and middle- income countries use a “2+ 1” vaccination schedule recommended by the World Health Organization.

Two primary doses are administered in infancy at six and 14 weeks of age. This is followed by one booster dose at nine months. The booster dose is needed to maintain immunity over years. Therefore, in designing our study, we considered dropping primary doses and not the booster dose.

Antibodies can prevent invasive pneumococcal disease. This is the basis for individual protection. Antibodies can also prevent carriage, or asymptomatic infection in the nasopharynx.

The level of antibodies needed to prevent carriage is likely higher than that needed to prevent disease. Preventing carriage in older children is thought to be the mechanism by which the vaccine induces herd immunity. This is because older children are the main reservoir of S pneumoniae and carriage is much more common than disease.

In our recent randomised trial, we tested two “1+ 1” schedules for the two currently licensed pneumococcal conjugate vaccines, PCV13 ( Prevnar 13) and PCV10 ( Synflorix). We tested dropping either the six- week dose or the 14- week dose from the original three- dose schedule.

We found that the 1+ 1 schedules were not inferior to the 2+ 1 dose schedule in the levels of antibodies post- booster. This finding suggests that herd immunity, once in place, can be maintained by the reduced schedules.