ABSTRACT
Introduction: Although significant improvements in the prevention of pneumococcal infections have been achieved in recent years, Streptococcus pneumoniae remains a leading cause of morbidity and mortality. To prevent S. pneumoniae infections, vaccines have been developed for several years.
Areas covered: In this review, the most important emerging problems regarding pneumococcal conjugate vaccines (PCVs) are discussed in addition to the status of new vaccine design and development. Given the medical, social and economic relevance of pneumococcal diseases, the availability of effective and safe vaccines against S. pneumoniae is a key objective of public health.
Expert opinion: Protein vaccines using agents different from capsular polysaccharides (CPs) or whole-cell vaccines seem to induce a broader immune response than PCVs and theoretically offer definitive solutions, as they can stimulate both humoral and cellular immunity. Moreover, these vaccines, particularly the whole-cell vaccine, are simpler to produce and significantly less expensive. However, the development of these preparations is very far from completion. It is highly likely that for a long time, no new safe and effective pneumococcal vaccines will be available. The best formulation of new pneumococcal vaccines has not been established. Consequently, an effort towards the expanded use of the available vaccines has to be made.
Article highlights
Streptococcus pneumoniae causes both invasive (meningitis, sepsis, bacteremic pneumonia, IPD) and non-invasive diseases (non-bacteremic pneumonia, otitis media, rhinosinusitis, non-IPD) with significant medical, social, and economic impacts.
The so-called pneumococcal conjugate vaccines (PCVs) have significantly reduced the total burden of pneumococcal infection, but have a number of limitations that preclude or significantly limit further improvement.
To overcome limitations of PCVs, a non-PCV approach for pneumococcal vaccine development was considered: increased knowledge of immunity against S. pneumoniae and the availability of more advanced technologies for vaccine preparation favoured a number of studies in this regard.
Highly conserved pneumococcal proteins, which are common to most, if not all, serotypes, are able to induce a protective immune response and were considered to be potentially optimal candidates for new effective vaccines.
The development of new protein-based preparations is presently far from conclusion because only phase 1 or 2 studies have been completed. The best formulation of these new vaccines has not been established. In most cases, the exact mechanisms with which the single proteins stimulate the immune system and interfere with S. pneumoniae colonization and infection are not precisely defined.
It is unlikely that all of the problems related to development of new pneumococcal vaccines will be solved. Consequently, an effort towards an expanded use of the available vaccines has to be made.
This box summarizes key points contained in the article.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. A reviewer on this manuscript has disclosed that they served as a consultant and speaker in addition to receiving grants from Pfizer, GlaxoSmithKline and Merck Sharp & Dohme.