scholarly journals A semisynthetic glycoconjugate provides expanded cross-serotype protection against Streptococcus pneumoniae

2021 ◽  
Author(s):  
Paulina M Kaplonek ◽  
Ling Yao ◽  
Katrin Reppe ◽  
Franziska M Voss ◽  
Thomas Kohler ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Bacterial Load ◽  
Large Animal Model ◽  
Pneumococcal Vaccines ◽  
Large Animal ◽  
Proof Of Concept ◽  
Additional Protection ◽  
Synthetic Oligosaccharides ◽  
Glycoconjugate Vaccine ◽  
Reduce Disease Severity

Streptococcus pneumoniae infections are the leading cause of child mortality globally. Current vaccines fail to induce a protective immune response towards a conserved part of the pathogen, resulting in new serotypes causing disease. Therefore, new vaccine strategies are urgently needed. Described is a two-pronged approach combining S.pneumoniae proteins, pneumolysin and PspA, with a precisely defined synthetic oligosaccharide, whereby the carrier protein acts as a serotype-independent antigen to provide additional protection. Proof of concept in mice and swine models revealed that the conjugates inhibit colonization of the nasopharynx, decrease the bacterial load and reduce disease severity in the bacteria challenged model. Immunization of piglets provided the first evidence for the immunogenicity and protective potential of synthetic glycoconjugate vaccine in a large animal model. A combination of synthetic oligosaccharides with proteins from the target pathogen opens the path to create broadly cross-protective ("universal") pneumococcal vaccines.

Mesenchymal stem cell derived exosomes in the treatment of synovitis: proof of concept in large animal model

2016 ◽  
Vol 33 (3) ◽  
pp. 409
Author(s):  
F. Javier Vela González ◽  
Francisco M. Sánchez-Margallo ◽  
Angelo Tapia-Araya ◽  
Rebeca Blázquez ◽  
Verónica Álvarez ◽  
...  
Keyword(s):  
Animal Model ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Large Animal Model ◽  
Large Animal ◽  
Proof Of Concept

scholarly journals Immunological and Epidemiological Aspects of the Immunogenicity of Streptococcus Pneumoniae Serotype 3 Capsular Polysaccharide in Pneumococcal Vaccines

2020 ◽  
Vol 97 (1) ◽  
pp. 72-82
Author(s):  
A. E. Zaitsev ◽  
E. A. Kurbatova ◽  
N. B. Egorova ◽  
E. V. Sukhova ◽  
N. E. Nifantiev
Keyword(s):  
Streptococcus Pneumoniae ◽  
Chemical Structure ◽  
Capsular Polysaccharide ◽  
Pneumococcal Vaccines ◽  
Immunization Schedule ◽  
Prophylactic Efficacy ◽  
National Immunization ◽  
The World ◽  
Synthetic Oligosaccharides ◽  
Immunization Programmes

The introduction of pneumococcal vaccines into national immunization programmes around the world has reduced the incidence of pneumococcal vaccine serotypes, but had no influence on the incidence of Streptococcus pneumoniae serotype 3 included in their composition. The results of evaluation of epidemiological efficacy and immunogenicity of capsular polysaccharide of S. pneumoniae serotype 3 capsular polysaccharide (CP) in conjugated and polysaccharide pneumococcal vaccines are contradictory. Some studies have shown the effectiveness of vaccination, other studies indicate insufficient immunogenicity and prophylactic efficacy of S. pneumoniae serotype 3 CP. The authors’ analysis of the results of clinical studies showed that the prophylactic efficacy of S. pneumoniae serotype 3 CP depends on the type of vaccine, nosological form of the disease, age, immunization schedule. According to the literature data, the most informative parameter of the protective activity of S. pneumoniae CP in pneumococcal vaccines, including serotype 3, is opsonophagocytosis. The experimental data of the low immunogenicity of serotype 3 CP, presumably associated with an unusual way of synthesis of its CP, are considered. To increase the im muno genicity of S. pneumoniae serotype 3 CP, the use of synthetic oligosaccharides of a strictly defined chemical structure corresponding to the protective fragments of serotype 3 CP and conjugated with a carrier protein for induction of T-dependent immune response and immunological memory is promising.

scholarly journals Immunological and Epidemiological Aspects of the Immunogenicity of Streptococcus Pneumoniae Serotype 3 Capsular Polysaccharide in Pneumococcal Vaccines

2020 ◽  
pp. 72-82
Author(s):  
A. E. Zaitsev ◽  
E. A. Kurbatova ◽  
N. B. Egorova ◽  
E. V. Sukhova ◽  
N. E. Nifantiev
Keyword(s):  
Streptococcus Pneumoniae ◽  
Chemical Structure ◽  
Capsular Polysaccharide ◽  
Pneumococcal Vaccines ◽  
Immunization Schedule ◽  
Prophylactic Efficacy ◽  
National Immunization ◽  
The World ◽  
Synthetic Oligosaccharides ◽  
Immunization Programmes

The introduction of pneumococcal vaccines into national immunization programmes around the world has reduced the incidence of pneumococcal vaccine serotypes, but had no influence on the incidence of Streptococcus pneumoniae serotype 3 included in their composition. The results of evaluation of epidemiological efficacy and immunogenicity of capsular polysaccharide of S. pneumoniae serotype 3 capsular polysaccharide (CP) in conjugated and polysaccharide pneumococcal vaccines are contradictory. Some studies have shown the effectiveness of vaccination, other studies indicate insufficient immunogenicity and prophylactic efficacy of S. pneumoniae serotype 3 CP. The authors’ analysis of the results of clinical studies showed that the prophylactic efficacy of S. pneumoniae serotype 3 CP depends on the type of vaccine, nosological form of the disease, age, immunization schedule. According to the literature data, the most informative parameter of the protective activity of S. pneumoniae CP in pneumococcal vaccines, including serotype 3, is opsonophagocytosis. The experimental data of the low immunogenicity of serotype 3 CP, presumably associated with an unusual way of synthesis of its CP, are considered. To increase the im muno genicity of S. pneumoniae serotype 3 CP, the use of synthetic oligosaccharides of a strictly defined chemical structure corresponding to the protective fragments of serotype 3 CP and conjugated with a carrier protein for induction of T-dependent immune response and immunological memory is promising.

scholarly journals Osseointegrated Transcutaneous Device for Amputees: A Pilot Large Animal Model

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Brian T. Grisez ◽  
Andrew E. Hanselman ◽  
Karim W. Boukhemis ◽  
Trapper A. J. Lalli ◽  
Brock A. Lindsey
Keyword(s):  
Histological Analysis ◽  
Large Animal Model ◽  
Large Animal ◽  
Proof Of Concept ◽  
Short Term ◽  
Bone Implant ◽  
Initial Surgery ◽  
Socket Interface ◽  
Transcutaneous Implant

Traditional above-the-knee amputation prosthetics utilize a stump-socket interface that is well-known for skin/socket problems, sitting difficulty, disuse osteopenia, and increased work of ambulation. As a result, we evaluated a novel osseointegrated transcutaneous implant in a large animal. The implant was designed to promote osseointegration at the bone-implant interface and minimize complications. As proof of concept, four Dorset sheep underwent a two-stage surgery for forelimb placement of an osseointegrated transcutaneous implant utilizing Compress® technology (Biomet, Inc., Warsaw, IN). Two sheep received a long anchor plug (90 mm long x 9 mm in diameter) and two received a short anchor plug (46 mm long x 9 mm in diameter). Sixteen weeks after the initial surgery, the operative limbs, along with the attached implant, underwent radiographic and histological analysis for osseointegration. Periprosthetic fractures occurred in the two animals that received the longer internal prosthesis; one healed with splinting and the other animal underwent a second surgical procedure to advance the amputation site more proximal. No fractures occurred in the shorter internal prosthesis group. There was no histological evidence of infection and none of the transcutaneous adapters failed. Bone-implant osseointegration was demonstrated in two of three limbs that underwent histological analysis. This unique implant demonstrated osseointegration without transcutaneous adapter failure, all while displaying minimal infection risk from the outside environment. Although it involved short-term follow-up in a limited number of animals, this pilot study provides a platform for further investigation into the valid concept of using Compress® technology as an endo-exo device.

scholarly journals A New Form of Decellularized Extracellular Matrix Hydrogel for Treating Ischemic Tissue via Intravascular Infusion

2020 ◽  
Author(s):  
Martin T. Spang ◽  
Tori S. Lazerson ◽  
Saumya Bhatia ◽  
James Corbitt ◽  
Gerardo Sandoval ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Left Ventricular ◽  
Large Animal Model ◽  
Left Ventricular Volumes ◽  
Large Animal ◽  
Proof Of Concept ◽  
Large Animal Models ◽  
Ischemic Tissue ◽  
New Form

AbstractExtracellular matrix (ECM) hydrogels have been widely used in preclinical studies as injectable materials for tissue engineering therapies. We have developed a new ECM therapy, the soluble fraction derived from decellularized, digested ECM, for intravascular infusion. This new form of ECM is capable of gelation in vivo and can be delivered acutely after an injury to promote cell survival and improve vascularization. In this study, we show proof-of-concept for the feasibility, safety, and efficacy of ECM infusions using small and large animal models of acute myocardial infarction (MI) and intracoronary infusion. Following infusion, the ECM material was retained in the heart, specifically in regions of ischemia, and colocalized with endothelial cells, coating the leaky microvasculature. Functional improvements, specifically reduced left ventricular volumes, were observed after ECM infusion post-MI. Genes associated with angiogenesis were upregulated, and genes associated with cell apoptosis/necrosis and fibrosis were downregulated. The ECM was also delivered using a clinically-relevant catheter in a large animal model of acute MI. This study shows proof-of-concept for a new intravascular delivery strategy for ECM biomaterial therapies with potential implications for a variety of pathologies with ischemic tissue or injured vasculature.

scholarly journals Improving vaccines against Streptococcus pneumoniae using synthetic glycans

2018 ◽  
Vol 115 (52) ◽  
pp. 13353-13358 ◽  
Author(s):  
Paulina Kaplonek ◽  
Naeem Khan ◽  
Katrin Reppe ◽  
Benjamin Schumann ◽  
Madhu Emmadi ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Vaccine Development ◽  
The Elderly ◽  
Protective Antibodies ◽  
Common Serotypes ◽  
Glycoconjugate Vaccines ◽  
Synthetic Oligosaccharides ◽  
Glycoconjugate Vaccine ◽  
The Stability

Streptococcus pneumoniae remains a deadly disease in small children and the elderly even though conjugate and polysaccharide vaccines based on isolated capsular polysaccharides (CPS) are successful. The most common serotypes that cause infection are used in vaccines around the world, but differences in geographic and demographic serotype distribution compromises protection by leading vaccines. The medicinal chemistry approach to glycoconjugate vaccine development has helped to improve the stability and immunogenicity of synthetic vaccine candidates for several serotypes leading to the induction of higher levels of specific protective antibodies. Here, we show that marketed CPS-based glycoconjugate vaccines can be improved by adding synthetic glycoconjugates representing serotypes that are not covered by existing vaccines. Combination (coformulation) of synthetic glycoconjugates with the licensed vaccines Prevnar13 (13-valent) and Synflorix (10-valent) yields improved 15- and 13-valent conjugate vaccines, respectively, in rabbits. A pentavalent semisynthetic glycoconjugate vaccine containing five serotype antigens (sPCV5) elicits antibodies with strong in vitro opsonophagocytic activity. This study illustrates that synthetic oligosaccharides can be used in coformulation with both isolated polysaccharide glycoconjugates to expand protection from existing vaccines and each other to produce precisely defined multivalent conjugated vaccines.

DEVELOPMENT OF A LARGE ANIMAL MODEL OF OPIATE ADDICTION TO EVALUATE CARDIOVASCULAR FUNCTION.

Analgesia ◽  
1995 ◽  
Vol 1 (4) ◽  
pp. 598-602 ◽  
Author(s):  
L.D. Napier ◽  
Z. Mateo ◽  
D.A. Yoshishige ◽  
B.A. Barron ◽  
J.L. Caffrey
Keyword(s):  
Animal Model ◽  
Cardiovascular Function ◽  
Large Animal Model ◽  
Opiate Addiction ◽  
Large Animal
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