scholarly journals Pneumococcal Choline-Binding Proteins Involved in Virulence as Vaccine Candidates

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 181
Author(s):  
Julio Sempere ◽  
Mirella Llamosí ◽  
Idoia del Río Menéndez ◽  
Beatriz López Ruiz ◽  
Mirian Domenech ◽  
...  

Streptococcus pneumoniae is a pathogen responsible for millions of deaths worldwide. Currently, the available vaccines for the prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV-23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes (up to 100 different serotypes have been identified) and are unable to protect against non-vaccine serotypes and non-encapsulated pneumococci. The emergence of antibiotic-resistant non-vaccine serotypes after these vaccines is an increasing threat. Therefore, there is an urgent need to develop new pneumococcal vaccines which could cover a wide range of serotypes. One of the vaccines most characterized as a prophylactic alternative to current PPV-23 or PCVs is a vaccine based on pneumococcal protein antigens. The choline-binding proteins (CBP) are found in all pneumococcal strains, giving them the characteristic to be potential vaccine candidates as they may protect against different serotypes. In this review, we have focused the attention on different CBPs as vaccine candidates because they are involved in the pathogenesis process, confirming their immunogenicity and protection against pneumococcal infection. The review summarizes the major contribution of these proteins to virulence and reinforces the fact that antibodies elicited against many of them may block or interfere with their role in the infection process.

1999 ◽  
Vol 67 (10) ◽  
pp. 5508-5513 ◽  
Author(s):  
Ting-Huai Wu ◽  
Xin-Xing Gu

ABSTRACT Nontypeable Haemophilus influenzae (NTHi) is a common cause of otitis media and respiratory tract infections. Outer membrane proteins (OMP) and lipooligosaccharide (LOS) are major surface antigens of NTHi and potential vaccine candidates. De-O-acylated LOS (dLOS) or oligosaccharide (OS) was coupled to total OMP to form dLOS-OMP and OS-OMP conjugates, while a dLOS-tetanus toxoid (TT) was synthesized for comparison. These conjugates were evaluated in mice and rabbits for immunogenicity. dLOS-OMP elicited a better boostable antibody response against LOS than did dLOS-TT, while OS-OMP was not immunogenic. Formulation of the conjugates with Ribi adjuvant significantly enhanced the immunogenicity of dLOS-OMP and dLOS-TT but not that of OS-OMP. In addition, rabbit antisera elicited by dLOS-OMP but not dLOS-TT (or OMP alone) demonstrated bactericidal activity against 40% of the NTHi strains tested. These results indicate that dLOS is a better derivative of LOS than OS and that OMP is a good carrier for NTHi LOS-based conjugate vaccines.


2000 ◽  
Vol 38 (4) ◽  
pp. 1319-1323 ◽  
Author(s):  
Elliot R. Lawrence ◽  
Cesar A. Arias ◽  
Brigid Duke ◽  
Dani Beste ◽  
Karen Broughton ◽  
...  

New pneumococcal conjugate vaccines covering a limited number of serotypes are likely to come into widespread use over the next few years. It is unknown what effect this will have on the relative importance of different serotypes as causes of pneumococcal infection. Hence, it will be important to monitor serotype prevalence before, during, and after the introduction of new vaccines. We have investigated the ability of a PCR method based on polymorphisms in two genes common to the different capsule loci to predict the serotype of 93 clinical isolates of Streptococcus pneumoniae submitted to the Central Public Health Laboratory in 1997. Of 70 isolates with vaccine serotypes, 65 were predicted to belong to the correct serotype; this number was improved to 69 with the inclusion of two additional patterns to the database. Of 23 isolates with other serotypes, 19 were correctly predicted as non-vaccine serotypes, the discrepancy lying with four isolates of 6A (non-vaccine serotype) that were indistinguishable from isolates of 6B (vaccine serotype). In situations in which culture of the organism is not feasible, this method could potentially be applicable directly to clinical specimens and could be a valuable aid to the surveillance of pneumococcal serotypes.


Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 132 ◽  
Author(s):  
Malihe Masomian ◽  
Zuleeza Ahmad ◽  
Lai Ti Gew ◽  
Chit Laa Poh

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.


2009 ◽  
Vol 78 (3) ◽  
pp. 1383-1389 ◽  
Author(s):  
Gabriella M. Scandurra ◽  
Geoffrey W. de Lisle ◽  
Sonia M. Cavaignac ◽  
May Young ◽  
R. Pamela Kawakami ◽  
...  

ABSTRACT Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the causative agent of paratuberculosis, a chronic enteritis of ruminants. To control the considerable economic effect that paratuberculosis has on the livestock industry, a vaccine that induces protection with minimal side effects is required. We employed transposon mutagenesis and allelic exchange to develop three potential vaccine candidates, which were then tested for virulence with macrophages, mice, and goats. All three models identified the WAg906 mutant as being the most attenuated, but some differences in the levels of attenuation were evident among the models when testing the other strains. In a preliminary mouse vaccine experiment, limited protection was induced by WAg915, as evidenced by a reduced bacterial load in spleens and livers 12 weeks following intraperitoneal challenge with M. paratuberculosis K10. While we found macrophages and murine models to be rapid and cost-effective alternatives for the initial screening of M. paratuberculosis mutants for attenuation, it appears necessary to do the definitive assessment of attenuation with a ruminant model.


2020 ◽  
Author(s):  
Maile T. Phillips ◽  
Joshua L. Warren ◽  
Noga Givon-Lavi ◽  
Adrienn Tothpal ◽  
Gili Regev-Yochay ◽  
...  

ABSTRACTStreptococcus pneumoniae remains a leading cause of morbidity and mortality. Pneumococcal conjugate vaccines (PCVs) are effective but target only a fraction of the more than 90 pneumococcal serotypes. As a result, the introduction of PCVs has been followed by the emergence of non-vaccine serotypes. With higher-valency PCVs currently under development, there is a need to understand and predict patterns of serotype replacement to anticipate future changes. In this study, we evaluated patterns of change in serotype prevalence post-PCV introduction in Israel. We found that the assumption that non-vaccine serotypes increase by the same proportion overestimates changes in serotype prevalence in Jewish and Bedouin children. Furthermore, pre-vaccine prevalence was positively associated with increases in prevalence over the study period. From our analyses, serotypes 12F, 8, 16F, 33F, 9N, 7B, 10A, 22F, 24F, and 17F were estimated to have gained the most cases of invasive pneumococcal disease through serotype replacement in the Jewish population. However, this model also failed to quantify some additional cases gained, suggesting that changes in carriage in children alone may be insufficient to explain serotype replacement in disease. Understanding of serotype replacement is important as higher-valency vaccines are introduced.


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