Pneumococcal

Streptococcus pneumoniae is one of the most burdensome human pathogens worldwide, claiming the lives of nearly 1 million children under the age of 5 each year. Since the implementation of pneumococcal polysaccharide conjugate vaccines (PCVs) in the routine vaccination of infants in developed nations (e.g., the US), the burden of the disease has dramatically decreased in those countries.

Figure 1. Burden of invasive pneumococcal disease in the United States.

However, pneumococcal disease is a scourge in low-income countries. Despite the success that routine use of PCVs have achieved in countries like the United States, where the incidence rate of invasive pneumococcal disease is less than 100 per 100,000 and the mortality rate is below 2% for children under 5, S. pneumoniae still remains a major global healthcare challenge for several reasons:

1. The manufacturing complexity for current PCVs results in pricing dilemmas in low- and middle-income markets. This is most noticeable in Africa, where both the incidence and mortality rates associated with pneumococcal disease are nearly 10-fold higher than in the United States.


Figure 2. Estimated global incidence rate of severe pneumoccal disease in children under 5 in 2010. Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700032/


Figure 3. Estimated global mortality rate of severe pneumoccal disease in children under 5 in 2010. Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700032/

 

2. Vaccination with PCVs prevents colonization by only a handful of the numerous S. pneumoniae serotypes (13 of the 95+). This results in serotype replacement by the other 82+ serotypes which necessitates continuous expansion of already complex vaccines.

3. Despite routine vaccination, breakthrough pneumococcal disease causes a significant economic burden in the United States with hundreds of thousands of hospitalizations that results in billions of dollars in total economic costs.

Our pneumococcal vaccine strategy represents an elegant solution that counteracts both of these deficiencies. Namely, we have developed an alternative conjugation strategy that can be performed at a fraction of the cost of current paradigms. To date, we have employed this approach to assemble a vaccine providing protection against colonization by >20 serotypes. We have enhanced this strategy with the inclusion of common-protein antigens that are highly up-regulated in virulent pneumococci (demonstrated protection against 70 serotypes separately). When combined, these two strategies provide a cheap and effective vaccine that prevents colonization by the deadliest S. pneumoniae serotypes while simultaneously providing direct protection against breakthrough pneumococcal disease.