Towards Elimination of Pneumococcal Disease
by Mark Alderson, Director of the Pneumococcal Vaccine Project at PATH, photos by Lauren Newhouse (PATH) and Mark Alderson (PATH)
Pneumococcal conjugate vaccines (PCVs) have now been introduced into many countries throughout the world, including in nearly 60 Gavi supported countries where these vaccines have markedly reduced childhood pneumococcal disease (including pneumonia). Despite this considerable success, two major challenges remain for global pneumococcal disease control—ensuring that PCVs are sustainably affordable for low- and middle-income countries (LMICs) and addressing disease caused by non-PCV serotypes.
Financial support provided by Gavi, the Vaccine Alliance and other donors has been instrumental in helping low-income countries (LICs) afford PCVs; however, many middle-income countries ineligible for Gavi assistance have struggled to afford them. A looming concern is that the same will happen for LICs when they graduate from Gavi support. We need inherently lower-cost PCVs to fill this gap. Competition from developing-country vaccine manufacturers (DCVMs) has solved this problem for other vaccines, but PCVs present unique manufacturing, clinical, and regulatory challenges that have thus far slowed DCVM entry into the PCV market. Fortunately, a number of DCVMs may now be on the brink of PCV licensure and World Health Organization prequalification—offering hope for competition and more efficient manufacturing processes that sustainably lower PCV costs for LMICs.
The other challenge is that non-vaccine serotypes have emerged to cause considerable residual pneumococcal disease in many areas where PCVs have been introduced. One proposed strategy for addressing this gap is to increase the number of PCV serotypes from the current 10 to 13 up to 15 to 24. This approach is challenging for LMICs, however, due to PCV manufacturing complexities and increased costs associated with adding serotypes. Moreover, continued serotype replacement is likely and the overall value of adding more serotypes remains to be determined. Another strategy is to develop vaccines based on common pneumococcal protein antigens to either replace or supplement PCVs. Although this strategy has shown some initial promise, considerable clinical and regulatory challenges remain and difficulties in demonstrating a clear-cut protective benefit in early-stage clinical trials leave many questions as of yet unanswered.
Is there a solution? Natural immunity to the pneumococcus involves immune responses to both the polysaccharide antigens used to make PCVs and to common pneumococcal proteins. For this reason, the best strategy may be to combine these approaches, either by adding proteins to PCVs or by using common proteins as the carrier for PCVs. The latter approach has less regulatory challenges and, as such, may be our best shot for a more comprehensive global pneumococcal disease control strategy. Overall, progress to date against pneumococcal disease is an inspiring testament to what is possible, but we must continue to pursue strategies for addressing remaining gaps so that no child dies of this preventable disease, anywhere.