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 Increased Immunogenicity of Full-Length Protein Antigens through Sortase-Mediated Coupling on the PapMV Vaccine Platform

Vaccines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 49 ◽  
Author(s):  
Marie-Ève Laliberté-Gagné ◽  
Marilène Bolduc ◽  
Ariane Thérien ◽  
Caroline Garneau ◽  
Philippe Casault ◽  
...  
Keyword(s):  
Immune Response ◽  
Cytotoxic T Lymphocyte ◽  
Specific Protein ◽  
Full Length ◽  
Protein Antigens ◽  
Vaccine Platform ◽  
Peptide Antigens ◽  
Viral Antigens ◽  
Covalently Linked ◽  
Papmv Nanoparticles

Background: Flexuous rod-shape nanoparticles—made of the coat protein of papaya mosaic virus (PapMV)—provide a promising vaccine platform for the presentation of viral antigens to immune cells. The PapMV nanoparticles can be combined with viral antigens or covalently linked to them. The coupling to PapMV was shown to improve the immune response triggered against peptide antigens (<39 amino acids) but it remains to be tested if large proteins can be coupled to this platform and if the coupling will lead to an immune response improvement. Methods: Two full-length recombinant viral proteins, the influenza nucleoprotein (NP) and the simian immunodeficiency virus group-specific protein antigen (GAG) were coupled to PapMV nanoparticles using sortase A. Mice were immunized with the nanoparticles coupled to the antigens and the immune response directed to the antigens were analyzed by ELISA and ELISPOT. Results: We showed the feasibility of coupling two different full-length proteins (GAG and NP) to the nanoparticle. We also showed that the coupling to PapMV nanoparticles improved significantly the humoral and the cytotoxic T lymphocyte (CTL) immune response to the antigens. Conclusion: This proof of concept demonstrates the versatility and the efficacy of the PapMV vaccine platform in the design of vaccines against viral diseases.

scholarly journals Microtubule Actin Cross-Linking Factor (Macf)

1999 ◽  
Vol 147 (6) ◽  
pp. 1275-1286 ◽  
Author(s):  
Conrad L. Leung ◽  
Dongming Sun ◽  
Min Zheng ◽  
David R. Knowles ◽  
Ronald K.H. Liem
Keyword(s):  
Calcium Binding ◽  
Coiled Coil ◽  
Specific Protein ◽  
Binding Domain ◽  
Full Length ◽  
Actin Binding ◽  
Cross Linking ◽  
Actin Binding Domain

We cloned and characterized a full-length cDNA of mouse actin cross-linking family 7 (mACF7) by sequential rapid amplification of cDNA ends–PCR. The completed mACF7 cDNA is 17 kb and codes for a 608-kD protein. The closest relative of mACF7 is the Drosophila protein Kakapo, which shares similar architecture with mACF7. mACF7 contains a putative actin-binding domain and a plakin-like domain that are highly homologous to dystonin (BPAG1-n) at its NH2 terminus. However, unlike dystonin, mACF7 does not contain a coiled–coil rod domain; instead, the rod domain of mACF7 is made up of 23 dystrophin-like spectrin repeats. At its COOH terminus, mACF7 contains two putative EF-hand calcium-binding motifs and a segment homologous to the growth arrest–specific protein, Gas2. In this paper, we demonstrate that the NH2-terminal actin-binding domain of mACF7 is functional both in vivo and in vitro. More importantly, we found that the COOH-terminal domain of mACF7 interacts with and stabilizes microtubules. In transfected cells full-length mACF7 can associate not only with actin but also with microtubules. Hence, we suggest a modified name: MACF (microtubule actin cross-linking factor). The properties of MACF are consistent with the observation that mutations in kakapo cause disorganization of microtubules in epidermal muscle attachment cells and some sensory neurons.

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 Comparative analysis of conventional and new seismically isolated structure

2021 ◽  
Vol 64 (3) ◽  
pp. 185-193
Author(s):  
Jelena Ristić ◽  
Miloš Vučinić ◽  
Danilo Ristić ◽  
Milutin Vučinić
Keyword(s):  
Seismic Isolation ◽  
Low Cost ◽  
Seismic Energy ◽  
Seismic Excitation ◽  
Isolation System ◽  
Vibration Period ◽  
International Projects ◽  
Dominant Period ◽  
Efficient Protection ◽  
Seismically Isolated

Extensive analytical and experimental research has been done by the authors directed to mitigation of the effects of earthquakes on structures. The research results mainly represent parts of the realized several related international projects. A selected part of the analytical studies directed to comparison between conventional and seismically isolated frame structures is presented in this paper. The responses of the applied newely developed advanced seismic isolation system HC-RMS-GOSEB to the simulated input excitation of three representative earthquakes of intensity 0.50g, have shown that it is very effective for construction of vibro-isolated and seismically resistant buildings, providing activated multistage seismic response and globally optimized seismic energy balance. Its application achieves an increase in the vibration period of the structure, far enough from the dominant period of seismic excitation. The results of the research confirm that this system is a potential solution for achieving low-cost and highly efficient protection of buildings.

Pro-/Anti-Inflammatory Bioactive Proteins and Peptides

2020 ◽  
pp. 106-141
Author(s):  
Fatma Esra Güneş
Keyword(s):  
Bioactive Peptides ◽  
Positive Impact ◽  
Antioxidant Properties ◽  
Specific Protein ◽  
Food Proteins ◽  
Protein Fragments ◽  
Beneficial Effects ◽  
Potential Benefits ◽  
Anti Inflammatory ◽  
New Generation

Bioactive peptides (BP) are specific protein fragments that can affect biological processes or substrates that have a positive impact on functions and conditions on body health. Plant and animal sources that contain physiologically active food proteins, native or processed, are rich sources of bioactive peptides. Bioactive peptides derived from food proteins have been demostrated to have variety of beneficial effects, such as anti-inflammatory and antioxidant properties. BP are accepted the new generation of biologically active regulators; they can prevent oxidation and microbial degradation in foods and furthermore improve quality of life by treating various diseases and disorders. The present review highlights the recent findings on the roles of various food-derived bioactive peptides in inflammation and oxidative stress and discuss the potential benefits and limitations of using these compounds against the burden of chronic diseases.

scholarly journals Opening the OPK Assay Gatekeeper: Harnessing Multi-Modal Protection by Pneumococcal Vaccines

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 203
Author(s):  
Riegler ◽  
Mann ◽  
Orihuela ◽  
Tuomanen
Keyword(s):  
Vaccine Development ◽  
Immunocompromised Host ◽  
Pneumococcal Vaccines ◽  
Immune Functions ◽  
Protective Activity ◽  
Protein Antigens ◽  
Single Function ◽  
Cellular Immune ◽  
Opsonophagocytic Killing ◽  
New Evidence

Pneumococcal vaccine development is driven by the achievement of high activity in a single gatekeeper assay: the bacterial opsonophagocytic killing (OPK) assay. New evidence challenges the dogma that anti-capsular antibodies have only a single function that predicts success. The emerging concept of multi-modal protection presents an array of questions that are fundamental to adopting a new vaccine design process. If antibodies have hidden non-opsonic functions that are protective, should these be optimized for better vaccines? What would protein antigens add to protective activity? Are cellular immune functions additive to antibodies for success? Do different organs benefit from different modes of protection? Can vaccine activities beyond OPK protect the immunocompromised host? This commentary raises these issues at a time when capsule-only OPK assay-based vaccines are increasingly seen as a limiting strategy.

scholarly journals Preclinical Evaluation of the Pht Proteins as Potential Cross-Protective Pneumococcal Vaccine Antigens

2010 ◽  
Vol 79 (1) ◽  
pp. 238-245 ◽  
Author(s):  
Fabrice Godfroid ◽  
Philippe Hermand ◽  
Vincent Verlant ◽  
Philippe Denoël ◽  
Jan T. Poolman
Keyword(s):  
Survival Rates ◽  
Pneumococcal Infection ◽  
Protein Family ◽  
Transfer Model ◽  
Pneumococcal Vaccines ◽  
Protein Antigens ◽  
Human Antibodies ◽  
Lung Colonization ◽  
Vaccine Antigens ◽  
Colonization Model

ABSTRACTCurrent pneumococcal vaccines are composed of capsular polysaccharides (PS) of various serotypes, either as free PS or as protein-PS conjugates. The use of pneumococcus protein antigens that are able to afford protection across the majority of serotypes is envisaged as a relevant alternative and/or complement to the polysaccharides. In this context, based on several studies, the Pht protein family emerged as relevant vaccine candidates. The purpose of the present study was to evaluate the Pht protein family in several preclinical mouse models. Immunization with these antigens was compared with immunization with other pneumococcal antigens, such as CbpA, PspA, and PsaA. In a nasopharyngeal colonization model and in a lung colonization model, the Phts were found to be superior to the other candidates in terms of efficacy of protection and serotype coverage. Likewise, vaccination with PhtD allowed higher animal survival rates after lethal intranasal challenge. Finally, a passive transfer model in which natural anti-PhtD human antibodies were transferred into mice demonstrated significant protection against lethal intranasal challenge. This indicates that natural anti-PhtD human antibodies are able to protect against pneumococcal infection. Our findings, together with the serotype-independent occurrence of the Phts, designate this protein family as valid candidate antigens to be incorporated in protein-based pneumococcal vaccines.

scholarly journals Studies on Immunomodulatory Effect of Casein Phospho Peptide Isolated from Cultured Dairy Product

2020 ◽  
pp. 28-40
Author(s):  
Indumathi Mullaiselvan ◽  
Vijayarani Kanagaraj ◽  
Saranya Sekar ◽  
Baskaran Dharmar ◽  
Rathnapraba Sambandan
Keyword(s):  
Amino Acid ◽  
Bioactive Peptides ◽  
Mononuclear Cells ◽  
Dairy Product ◽  
Fermented Milk ◽  
Specific Protein ◽  
Immunomodulatory Effect ◽  
Peripheral Blood Mononuclear ◽  
Protein Fragments ◽  
Ft Ir

Bioactive peptides have been defined as specific protein fragments that have an impact on body functions or conditions and may ultimately influence health. Fermented milk is a dairy product which has abundance of bioactive peptides. In this study, Casein Phospho peptide (CPP) was isolated by enzymatic hydrolysis of fermented milk using trypsin. The molecular weight of the Casein Phospho peptide was 3.5 KDa. The anti-bacterial activity of Casein Phospho peptide was determined using four pathogens such as, Escherichia coli, Bacillus cereus, Staphylococcus aureus and Salmonella enterica. Casein phospho peptide formed a zone of inhibition against the pathogens. The bioactive peptides were characterized using Fourier Transform Infra-Red Spectroscopy (FT-IR), Casein Phospho peptide had aliphatic amine, acetyl amino I and acetyl amino II functional groups. The HPLC analysis of Casein Phospho peptide revealed that the major amino acid present was L- Glutamic acid and the amino acid present in lesser concentration was Leucine. Peripheral Blood Mononuclear Cells (PBMCs) were isolated from human blood and the cells were treated with Casein Phospho peptide to assess the immunomodulatory effect. Casein Phospho peptide was able to produce a higher concentration of IL-10 anti-inflammatory cytokines when treated with PBMCs.

Sign in / Sign up

Export Citation Format

Share Document