Abstract
Streptococcus pneumoniae is a major pathogen causing pneumonia with over 2 million deaths annually, especially in young children and the elderly. To date, at least 98 different pneumococcal capsular serotypes have been identified. Currently, the vaccines for prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes and are unable to protect against non-vaccine serotypes and unencapsulated S. pneumoniae. This has led to a rapid increase in antibiotic-resistant non-vaccine serotypes. Hence, there is an urgent need to develop new, effective, and affordable pneumococcal vaccines, which could cover a wide range of serotypes. This review discusses the new approaches to develop effective vaccines with broad serotype coverage as well as recent development of promising pneumococcal vaccines in clinical trials. New vaccine candidates are the inactivated whole-cell vaccine strain (Δpep27ΔcomD mutant) constructed by mutations of specific genes and several protein-based S. pneumoniae vaccines using conserved pneumococcal antigens, such as lipoprotein and surface-exposed protein (PspA). Among the vaccines in Phase 3 clinical trials are the pneumococcal conjugate vaccines, PCV-15 (V114) and 20vPnC. The inactivated whole-cell and several protein-based vaccines are either in Phase 1 or 2 trials. Furthermore, the recent progress of nanoparticles that play important roles as delivery systems and adjuvants to improve the performance, as well as the immunogenicity of the nanovaccines, are reviewed.
Highlights
Streptococcus pneumoniae or pneumococcus is a common human pathogen contributing to significant morbidity and mortality annually, especially in children, the elderly, and the immunocompromised [1].S. pneumoniae remains the leading cause of community-acquired pneumonia (CAP) despite the worldwide administration of pneumococcal vaccines [2]
Tada et al showed that the cationic liposomes (DOTAP/DC-chol liposomes) were able to enhance the delivery of Pneumococcal surface protein A (PspA) to nasal dendritic cells of mice and conferred complete protection against lethal infection S. pneumoniae
Gold nanoparticles carrying 45% of tetrasaccharide derived from the S. pneumonia type 14 capsular polysaccharide (Pn14PS) and 5% ovalbumin 323–339 peptide (OVA323–339 ) were able to elicit antibodies that promoted the phagocytosis of the pneumococcus
Summary
Streptococcus pneumoniae or pneumococcus is a common human pathogen contributing to significant morbidity and mortality annually, especially in children, the elderly, and the immunocompromised [1]. S. pneumoniae remains the leading cause of community-acquired pneumonia (CAP) despite the worldwide administration of pneumococcal vaccines [2]. S. pneumoniae can cause a myriad of non-invasive and invasive diseases. Non-invasive pneumococcal diseases include sinusitis, acute otitis media, and pneumonia that is localized to the lungs [3,4]. The invasive form of pneumococcal pneumonia can lead to bacteremia and meningitis [3]. In the US, pneumococcal sepsis and meningitis contributed to a few thousand deaths annually in adults. The 10 most common types cause 62% of invasive disease worldwide [7]
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