scholarly journals Proteomic technologies in the development of new vaccines based on serotype-non-specific protein antigens of Streptococcus pneumoniae

2019 ◽  
Vol 100 (4) ◽  
pp. 680-688
Author(s):  
Yu A Tyuri ◽  
A Z Zaripova ◽  
G Sh Isaeva ◽  
I G Mustafin ◽  
L T Bayazitova
Keyword(s):  
Full Range ◽  
Risk Groups ◽  
Specific Protein ◽  
Production Costs ◽  
New Combination ◽  
Protein Antigens ◽  
Pneumococcal Infections ◽  
Iga1 Protease ◽  
Combination Vaccines ◽  
New Vaccines

The review presents a modern strategy to improve the means of vaccine prevention of streptococcal infections aimed at finding and developing new vaccines for immunization of people belonging to risk groups. It should be noted that pneumococci (S. pneumoniae) are members of gram-positive bacteria (diplococci) and become the main cause of various nosological forms of human infectious diseases (such as pneumonia, otitis media, sinusitis, bacteremia and meningitis). Existing pneumococcal vaccines (conjugate and polysaccharide) have some important limitations, for example, serotype dependence, loss of effectiveness due to a change in the serotype landscape, insufficient protective effect from non-invasive forms of pneumococcal infections and high production costs associated with the development of these products. The main part of the review presents the most important research papers that used modern proteomic technologies in the study of the S. pneumoniae proteomic profile. These works allow us to evaluate at the molecular level the importance of bacterial proteins as candidates for creating new combination vaccines that can effectively protect against the full range of pneumococcal serotypes circulating in the human population. So, in particular, the data are provided on the new methodology for the analysis of the proteome of extracellular S. pneumoniae bacterial microvesicles to identify immunoreactive protein antigens, potential candidates for inclusion into vaccines. As a result of these studies, 15 immunoreactive proteins were discovered, 7 of which are cytosolic and 8 proteins are bound to the cell surface (MalX, ABC transporter or substrate binding transport protein, AmiA, AliA, LytC, IgA1 protease, PspA and the putative precursor of β-galactosidase). These are possible candidates for developing combination vaccines. Additionally, the review presents data on the role of significant virulence factors of the protein nature of S. pneumoniae strains in nasopharyngeal colonization, increased infectivity, as well as on overcoming reactions of the host's immune response.

scholarly journals A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens

2016 ◽  
Vol 21 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Calvin C. Daniels ◽  
P. David Rogers ◽  
Chasity M. Shelton
Keyword(s):  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Invasive Disease ◽  
Polysaccharide Vaccine ◽  
Pneumococcal Vaccines ◽  
Protein Antigens ◽  
Pneumococcal Infections ◽  
Serotype Replacement ◽  
Vaccine Recommendations ◽  
Vaccine Antigens

This review describes development of currently available pneumococcal vaccines, provides summary tables of current pneumococcal vaccine recommendations in children and adults, and describes new potential vaccine antigens in the pipeline. Streptococcus pneumoniae, the bacteria responsible for pneumonia, otitis media, meningitis and bacteremia, remains a cause of morbidity and mortality in both children and adults. Introductions of unconjugated and conjugated pneumococcal polysaccharide vaccines have each reduced the rate of pneumococcal infections caused by the organism S. pneumoniae. The first vaccine developed, the 23-valent pneumococcal polysaccharide vaccine (PPSV23), protected adults and children older than 2 years of age against invasive disease caused by the 23 capsular serotypes contained in the vaccine. Because PPSV23 did not elicit a protective immune response in children younger than 2 years of age, the 7-valent pneumococcal conjugate vaccine (PCV7) containing seven of the most common serotypes from PPSV23 in pediatric invasive disease was developed for use in children younger than 2 years of age. The last vaccine to be developed, the 13-valent pneumococcal conjugate vaccine (PCV13), contains the seven serotypes in PCV7, five additional serotypes from PPSV23, and a new serotype not contained in PPSV23 or PCV7. Serotype replacement with virulent strains that are not contained in the polysaccharide vaccines has been observed after vaccine implementation and stresses the need for continued research into novel vaccine antigens. We describe eight potential protein antigens that are in the pipeline for new pneumococcal vaccines.

scholarly journals Novel Protein-Based Pneumococcal Vaccines: Assessing the Use of Distinct Protein Fragments Instead of Full-Length Proteins as Vaccine Antigens

Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 9 ◽  
Author(s):  
Theano Lagousi ◽  
Paraskevi Basdeki ◽  
John Routsias ◽  
Vana Spoulou
Keyword(s):  
Low Cost ◽  
Specific Protein ◽  
Full Length ◽  
Pneumococcal Vaccines ◽  
Protein Antigens ◽  
Protein Fragments ◽  
Humoral And Cellular Immunity ◽  
Expression Variability ◽  
Efficient Protection ◽  
Antigenic Regions

Non-serotype-specific protein-based pneumococcal vaccines have received extensive research focus due to the limitations of polysaccharide-based vaccines. Pneumococcal proteins (PnPs), universally expressed among serotypes, may induce broader immune responses, stimulating humoral and cellular immunity, while being easier to manufacture and less expensive. Such an approach has raised issues mainly associated with sequence/level of expression variability, chemical instability, as well as possible undesirable reactogenicity and autoimmune properties. A step forward employs the identification of highly-conserved antigenic regions within PnPs with the potential to retain the benefits of protein antigens. Besides, their low-cost and stable construction facilitates the combination of several antigenic regions or peptides that may impair different stages of pneumococcal disease offering even wider serotype coverage and more efficient protection. This review discusses the up-to-date progress on PnPs that are currently under clinical evaluation and the challenges for their licensure. Focus is given on the progress on the identification of antigenic regions/peptides within PnPs and their evaluation as vaccine candidates, accessing their potential to overcome the issues associated with full-length protein antigens. Particular mention is given of the use of newer delivery system technologies including conjugation to Toll-like receptors (TLRs) and reformulation into nanoparticles to enhance the poor immunogenicity of such antigens.

scholarly journals Effects of Ageing and Gender on Naturally Acquired Antibodies to Pneumococcal Capsular Polysaccharides and Virulence-Associated Proteins

2008 ◽  
Vol 15 (9) ◽  
pp. 1391-1397 ◽  
Author(s):  
Birgit Simell ◽  
Mika Lahdenkari ◽  
Antti Reunanen ◽  
Helena Käyhty ◽  
Merja Väkeväinen
Keyword(s):  
Bacterial Infections ◽  
The Elderly ◽  
Capsular Polysaccharides ◽  
Protein Antigens ◽  
Pneumococcal Infections ◽  
Younger Adults ◽  
Associated Proteins ◽  
Normal Human ◽  
And Gender ◽  
Increased Susceptibility

ABSTRACT Elderly individuals are susceptible to pneumococcal infections. Although factors contributing to the increased susceptibility of the elderly to bacterial infections may be several, compromised immune function, a consequence of normal human ageing, is widely accepted to play a role. We evaluated the effect of ageing on the concentrations of naturally acquired antibodies to pneumococcal capsular polysaccharides (PPS) and protein antigens. The concentrations of immunoglobulin G (IgG) and IgM antibodies to the PPS of serotypes 3, 4, 6B, 9V, 14, and 23F and IgG antibodies to the pneumococcal virulence-associated proteins CbpA, LytC, PhtD and its C-terminal fragment (PhtD C), NanA, PspA fam1, and PspA fam2 were measured by enzyme immunoassay in the sera of younger (30 to 64 years of age) and elderly (65 to 97 years of age) adults. The concentrations of anti-PPS IgG against serotypes 3 and 6B, of anti-PPS IgM against serotypes 3, 4, 6B, 9V, and 23F, and of anti-protein IgG against all tested antigens were significantly lower in the elderly than in younger adults. A stronger decline in anti-PPS antibody concentrations was seen with age in women compared to men, while anti-protein antibody concentrations were mainly similar between the genders. Age, gender, and the nature of the antigen have substantial and varying effects on the antibody concentrations in the sera of adults.

New Combination Vaccines: Integration into Pediatric Practice

2007 ◽  
Vol 26 (12) ◽  
pp. 1149-1150 ◽  
Author(s):  
Virginia M. Pierce ◽  
Marietta Vázquez
Keyword(s):  
New Combination ◽  
Pediatric Practice ◽  
Combination Vaccines

scholarly journals Interaction of Pneumococcal Histidine Triad Proteins with Human Complement

2010 ◽  
Vol 78 (5) ◽  
pp. 2089-2098 ◽  
Author(s):  
Merit Melin ◽  
Emmanuel Di Paolo ◽  
Leena Tikkanen ◽  
Hanna Jarva ◽  
Cecile Neyt ◽  
...  
Keyword(s):  
Factor H ◽  
Surface Proteins ◽  
Bacterial Cells ◽  
Wild Type ◽  
Protein Antigens ◽  
Pneumococcal Infections ◽  
Relative Contribution ◽  
Bacterial Lysates ◽  
Affect Factor ◽  
Complement Deposition

ABSTRACT The pneumococcal histidine triad (Pht) proteins PhtA, PhtB, PhtD, and PhtE form a group of conserved pneumococcal surface proteins. Humans produce antibodies to Pht proteins upon exposure to pneumococcus, and immunization of mice has provided protective immunity against sepsis and pneumonia and reduced nasopharyngeal colonization. Pht proteins are candidates for inclusion in multicomponent pneumococcal protein vaccines. Their biological function in pneumococcal infections is not clear, but a role in complement inhibition has been suggested. We measured complement deposition on wild-type and Pht mutant strains in four genetic backgrounds: Streptococcus pneumoniae D39 (serotype 2) and R36A (unencapsulated derivative of D39) and strains of serotypes 3, 4, and 19F. PspA and PspC single and double mutants were compared to the wild-type and Pht-deficient D39 strains. Factor H binding was measured to bacterial cells, lysates, and protein antigens. Deletion of all four Pht proteins (Pht−) resulted in increased C3 deposition on the serotype 4 strain but not on the other strains. Pht antigens did not bind factor H, and deletion of Pht proteins did not affect factor H binding by bacterial lysates. The Pht− mutant serotype 4 strain bound slightly less factor H than the wild-type strain when binding was measured by flow cytometry. Pht proteins may play a role in immune evasion, but the mechanism of function is unlikely to be mediated by factor H binding. The relative contribution of Pht proteins to the inhibition of complement deposition is likely to be affected by the presence of other pneumococcal proteins and to depend on the genetic background.

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