The long search for a serotype independent pneumococcal vaccine.

Introduction: Serotype replacement - a consequence of polysaccharide vaccine use - will continue to drive the inclusion of new serotypes on conjugate vaccines, increasing production complexity and costs, and making an already expensive vaccine less accessible to developing countries, where prevalence is higher and resources available for health systems, scarcer. Serotype-independent formulations are a promising option, but so far they have not been successful in reducing colonization/transmission.Areas covered: Protein-based and whole-cell vaccine candidates studied in the past 30 years. Challenges for serotype-independent vaccine development and alternative approaches.Expert opinion: Clinical trials performed so far demonstrated the importance to establish more reliable animal models and better correlates of protection. Defining appropriate endpoints for clinical trials of serotype-independent vaccine candidates has been a challenge. Inhibition of colonization has been evaluated, but concern on the extent of bacterial elimination is still a matter of debate. Challenges on establishing representative sites for clinical trials, sample sizes and appropriate age groups are discussed. On a whole, although many challenges will have to be overcome, establishing protein-based antigens as serotype-independent vaccines is still the best alternative against the huge burden of pneumococcal diseases in the world.

The long search for a serotype independent pneumococcal vaccine

Introduction: Serotype replacement – a consequence of polysaccharide vaccine use – will continue to drive the inclusion of new serotypes on conjugate vaccines, increasing production complexity and costs, and making an already expensive vaccine less accessible to developing countries, where prevalence is higher and resources available for health systems, scarcer. Serotype-independent formulations are a promising option, but so far they have not been successful in reducing colonization/transmission.Areas covered: Protein-based and whole-cell vaccine candidates studied in the past 30 years. Challenges for serotype-independent vaccine development and alternative approaches.Expert opinion: Clinical trials performed so far demonstrated the importance to establish more reliable animal models and better correlates of protection. Defining appropriate endpoints for clinical trials of serotype-independent vaccine candidates has been a challenge. Inhibition of colonization has been evaluated, but concern on the extent of bacterial elimination is still a matter of debate. Challenges on establishing representative sites for clinical trials, sample sizes and appropriate age groups are discussed. On a whole, although many challenges will have to be overcome, establishing protein-based antigens as serotype-independent vaccines is still the best alternative against the huge burden of pneumococcal diseases in the world

The long search for a serotype independent pneumococcal vaccine

Introduction: Serotype replacement – a consequence of polysaccharide vaccine use – will continue to drive the inclusion of new serotypes on conjugate vaccines, increasing production complexity and costs, and making an already expensive vaccine less accessible to developing countries, where prevalence is higher and resources available for health systems, scarcer. Serotype-independent formulations are a promising option, but so far they have not been successful in reducing colonization/transmission.Areas covered: Protein-based and whole-cell vaccine candidates studied in the past 30 years. Challenges for serotype-independent vaccine development and alternative approaches.Expert opinion: Clinical trials performed so far demonstrated the importance to establish more reliable animal models and better correlates of protection. Defining appropriate endpoints for clinical trials of serotype-independent vaccine candidates has been a challenge. Inhibition of colonization has been evaluated, but concern on the extent of bacterial elimination is still a matter of debate. Challenges on establishing representative sites for clinical trials, sample sizes and appropriate age groups are discussed. On a whole, although many challenges will have to be overcome, establishing protein-based antigens as serotype-independent vaccines is still the best alternative against the huge burden of pneumococcal diseases in the world

Combined effects of lactoferrin and lysozyme on Streptococcus pneumoniae killing.

Streptococcus pneumoniae is a common colonizer of the human nasopharynx, which can occasionally spread to sterile sites, causing diseases such as otitis media, sinusitis, pneumonia, meningitis and bacteremia. Human apolactoferrin (ALF) and lysozyme (LZ) are two important components of the mucosal innate immune system, exhibiting lytic effects against a wide range of microorganisms. Since they are found in similar niches of the host, it has been proposed that ALF and LZ could act synergistically in controlling bacterial spread throughout the mucosa. The combination of ALF and LZ has been shown to enhance killing of different pathogens in vitro, with ALF facilitating the latter action of LZ. The aim of the present work was to investigate the combined effects of ALF and LZ on S pneumoniae. Concomitant addition of ALF and LZ had a synergistic killing effect on one of the pneumococci tested. Furthermore, the combination of ALF and ALZ was more bactericidal than lysozyme alone in all pneumococcal strains. Pneumococcal surface protein A (PspA), an important vaccine candidate, partially protects pneumococci from ALF mediated killing, while antibodies against one PspA enhance killing of the homologous strain by ALF. However, the serological variability of this molecule could limit the effect of anti-PspA antibodies on different pneumococci. Therefore, we investigated the ability of anti-PspA antibodies to increase ALF-mediated killing of strains that express different PspAs, and found that antisera to the N-terminal region of PspA were able to increase pneumococcal lysis by ALF, independently of the sequence similarities between the molecule expressed on the bacterial surface and that used to produce the antibodies. LF binding to the pneumococcal surface was confirmed by flow cytometry, and found to be inhibited in presence of anti-PspA antibodies. On a whole, the results suggest a contribution of ALF and LZ to pneumococcal clearance, and confirm PspA's ability to interact with ALF.