scholarly journals Biochemical and Immunological Evaluation of Recombinant CS6-Derived Subunit EnterotoxigenicEscherichia coliVaccine Candidates

2019 ◽  
Vol 87 (3) ◽  
Author(s):  
Steven T. Poole ◽  
Milton Maciel ◽  
Premkumar Dinadayala ◽  
Kathleen E. Dori ◽  
Annette L. McVeigh ◽  
...  
Keyword(s):  
Immune Responses ◽  
Recombinant Proteins ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Vaccine Strategy ◽  
Content Type ◽  
A Subunit ◽  
Folded Proteins ◽  
Immunological Evaluation

ABSTRACTCS6, a prevalent surface antigen expressed in nearly 20% of clinical enterotoxigenicEscherichia coli(ETEC) isolates, is comprised of two major subunit proteins, CssA and CssB. Using donor strand complementation, we constructed a panel of recombinant proteins of 1 to 3 subunits that contained combinations of CssA and/or CssB subunits and a donor strand, a C-terminal extension of 16 amino acids that was derived from the N terminus of either CssA or CssB. While the entire panel of recombinant proteins could be obtained as soluble, folded proteins, it was observed that the proteins possessing a heterologous donor strand, derived from the CS6 subunit different from the C-terminal subunit, had the highest degree of physical and thermal stability. Immunological characterization of the proteins, using a murine model, demonstrated that robust anti-CS6 immune responses were generated from fusions containing both CssA and CssB. Proteins containing only CssA were weakly immunogenic. Heterodimers, i.e., CssBA and CssAB, were sufficient to recapitulate the anti-CS6 immune response elicited by immunization with CS6, including the generation of functional neutralizing antibodies, as no further enhancement of the response was obtained with the addition of a third CS6 subunit. Our findings here demonstrate the feasibility of including a recombinant CS6 subunit protein in a subunit vaccine strategy against ETEC.

scholarly journals Coagulases as Determinants of Protective Immune Responses against Staphylococcus aureus

2012 ◽  
Vol 80 (10) ◽  
pp. 3389-3398 ◽  
Author(s):  
Molly McAdow ◽  
Andrea C. DeDent ◽  
Carla Emolo ◽  
Alice G. Cheng ◽  
Barry N. Kreiswirth ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Von Willebrand Factor ◽  
Subunit Vaccine ◽  
Gene Sequences ◽  
Content Type ◽  
A Subunit ◽  
Von Willebrand ◽  
Willebrand Factor

ABSTRACTDuring infection,Staphylococcus aureussecretes two coagulases (Coa and von Willebrand factor binding protein [vWbp]), which, following an association with host prothrombin and fibrinogen, form fibrin clots and enable the establishment of staphylococcal disease. Within the genomes of differentS. aureusisolates, coagulase gene sequences are variable, and this has been exploited for a classification of types. We show here that antibodies directed against the variable prothrombin binding portion of coagulases confer type-specific immunity through the neutralization ofS. aureusclotting activity and protection from staphylococcal disease in mice. By combining variable portions of coagulases from North American isolates into hybrid Coa and vWbp proteins, a subunit vaccine that provided protection against challenge with different coagulase-typeS. aureusstrains in mice was derived.

scholarly journals Subunit Approach to Evaluation of the Immune Protective Potential of Leptospiral Antigens

2011 ◽  
Vol 18 (12) ◽  
pp. 2026-2030 ◽  
Author(s):  
Samuel R. Félix ◽  
Daiane D. Hartwig ◽  
Ana Paula C. Argondizzo ◽  
Éverton F. Silva ◽  
Fabiana K. Seixas ◽  
...  
Keyword(s):  
Immune Responses ◽  
Recombinant Proteins ◽  
Subunit Vaccine ◽  
Lethal Dose ◽  
Leptospira Interrogans ◽  
Significant Protection ◽  
Genome Sequences ◽  
Hamster Model ◽  
Content Type ◽  
The World

ABSTRACTLeptospirosis is the most widespread zoonosis in the world. Current vaccines are based on whole-cell preparations that cause severe side effects and do not induce satisfactory immunity. In light of the leptospiral genome sequences recently made available, several studies aimed at identification of protective recombinant immunogens have been performed; however, few such immunogens have been identified. The aim of this study was to evaluate 27 recombinant antigens to determine their potential to induce an immune response protective against leptospirosis in the hamster model. Experiments were conducted with groups of female hamsters immunized with individual antigen preparations. Hamsters were then challenged with a lethal dose ofLeptospira interrogans. Thirteen antigens induced protective immune responses; however, only recombinant proteins LIC10325 and LIC13059 induced significant protection against mortality. These results have important implications for the development of an efficacious recombinant subunit vaccine against leptospirosis.

scholarly journals Development of Neutralizing Monoclonal Antibodies for Oncogenic Human Papillomavirus Types 31, 33, 45, 52, and 58

2014 ◽  
Vol 21 (4) ◽  
pp. 587-593 ◽  
Author(s):  
Martha J. Brown ◽  
Hanna Seitz ◽  
Victoria Towne ◽  
Martin Müller ◽  
Adam C. Finnefrock
Keyword(s):  
Monoclonal Antibodies ◽  
Human Papillomavirus ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Cervical Cancers ◽  
Hpv Types ◽  
Oncogenic Hpv ◽  
Neutralizing Epitopes ◽  
Selection Of

ABSTRACTHuman papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant number of other anogenital cancers, and a growing number of head and neck cancers. Two licensed vaccines offer protection against the most prevalent oncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer cases worldwide and one of these also offers protection against types 6 and 11, responsible for 90% of genital warts. The vaccines are comprised of recombinantly expressed major capsid proteins that self-assemble into virus-like particles (VLPs) and prevent infection by eliciting neutralizing antibodies. Adding the other frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccine would increase the coverage against HPV-induced cancers to approximately 90%. We describe the generation and characterization of panels of monoclonal antibodies to these five additional oncogenic HPV types, and the selection of antibody pairs that were high affinity and type specific and recognized conformation-dependent neutralizing epitopes. Such characteristics make these antibodies useful tools for monitoring the production and potency of a prototype vaccine as well as monitoring vaccine-induced immune responses in the clinic.

scholarly journals Mucosal Targeting of a BoNT/A Subunit Vaccine Adjuvanted with a Mast Cell Activator Enhances Induction of BoNT/A Neutralizing Antibodies in Rabbits

PLoS ONE ◽  
2011 ◽  
Vol 6 (1) ◽  
pp. e16532 ◽  
Author(s):  
Herman F. Staats ◽  
Jeffrey R. Fielhauer ◽  
Afton L. Thompson ◽  
Alice A. Tripp ◽  
Ashley E. Sobel ◽  
...  
Keyword(s):  
Mast Cell ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
A Subunit ◽  
Cell Activator ◽  
Mast Cell Activator

scholarly journals Protection against Lethal Leptospirosis after Vaccination with LipL32 Coupled or Coadministered with the B Subunit of Escherichia coli Heat-Labile Enterotoxin

2012 ◽  
Vol 19 (5) ◽  
pp. 740-745 ◽  
Author(s):  
André A. Grassmann ◽  
Samuel R. Félix ◽  
Carolina Ximendes dos Santos ◽  
Marta G. Amaral ◽  
Amilton C. P. Seixas Neto ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Response ◽  
Subunit Vaccine ◽  
Lethal Dose ◽  
Control Group ◽  
Hamster Model ◽  
Content Type ◽  
B Subunit ◽  
Heat Labile ◽  
A Subunit

ABSTRACTLeptospirosis, a worldwide zoonosis, lacks an effective, safe, and cross-protective vaccine. LipL32, the most abundant, immunogenic, and conserved surface lipoprotein present in all pathogenic species ofLeptospira, is a promising antigen candidate for a recombinant vaccine. However, several studies have reported a lack of protection when this protein is used as a subunit vaccine. In an attempt to enhance the immune response, we used LipL32 coupled to or coadministered with the B subunit of theEscherichia coliheat-labile enterotoxin (LTB) in a hamster model of leptospirosis. After homologous challenge with 5× the 50% lethal dose (LD50) ofLeptospira interrogans, animals vaccinated with LipL32 coadministered with LTB and LTB::LipL32 had significantly higher survival rates (P< 0.05) than animals from the control group. This is the first report of a protective immune response afforded by a subunit vaccine using LipL32 and represents an important contribution toward the development of improved leptospirosis vaccines.

Penton base induces better protective immune responses than fiber and hexon as a subunit vaccine candidate against adenoviruses

Vaccine ◽  
2018 ◽  
Vol 36 (29) ◽  
pp. 4287-4297 ◽  
Author(s):  
Kai Hu ◽  
Ming Fu ◽  
Xinmeng Guan ◽  
Di Zhang ◽  
Xu Deng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Penton Base ◽  
A Subunit

Construction and immunogenic studies of a mFc fusion receptor binding domain (RBD) of spike protein as a subunit vaccine against SARS-CoV-2 infection

2020 ◽  
Vol 56 (61) ◽  
pp. 8683-8686 ◽  
Author(s):  
Xiaoxiao Qi ◽  
Bixia Ke ◽  
Qian Feng ◽  
Deying Yang ◽  
Qinghai Lian ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fusion Protein ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Humoral And Cellular Immunity ◽  
A Subunit

Herein, we report that a recombinant fusion protein, containing a 457 amino acid SARS-CoV-2 receptor binding domain and a mouse IgG1 Fc domain, could induce highly potent neutralizing antibodies and stimulate humoral and cellular immunity in mice.

Functional and immunological evaluation of two novel proteins of Leptospira spp.

Microbiology ◽  
2014 ◽  
Vol 160 (1) ◽  
pp. 149-164 ◽  
Author(s):  
Luis G. V. Fernandes ◽  
Monica L. Vieira ◽  
Ivy J. Alves ◽  
Zenaide M. de Morais ◽  
Silvio A. Vasconcellos ◽  
...  
Keyword(s):  
Recombinant Proteins ◽  
Cellular Localization ◽  
Serum Samples ◽  
Novel Proteins ◽  
Metal Affinity ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Surface Adhesins ◽  
Immunological Evaluation

This work shows the production and characterization of two novel putative lipoproteins encoded by the genes LIC10645 and LIC10731 identified in the genome sequences of Leptospira interrogans. In silico conservation analysis indicated that the proteins are well conserved among pathogenic leptospiral serovars and species. Recombinant proteins were obtained in Escherichia coli BL21(DE3) Star pLysS strain, purified by metal-affinity chromatography, and used for characterization and immunological evaluations. Recombinant proteins were capable of eliciting a combination of humoral and cellular immune responses in animal models, and could be recognized by antibodies present in human serum samples. The recombinant proteins Lsa44 and Lsa45 were able to bind laminin, and were named Lsa44 and Lsa45 for leptospiral surface adhesins of 44 and 45 kDa, respectively. The attachment to laminin was dose-responsive with K D values of 108.21 and 250.38 nM for Lsa44 and Lsa45, respectively. Moreover, these proteins interact with plasminogen (PLG) with K D values of 53.56 and 36.80 nM, respectively. PLG bound to the recombinant proteins could be converted to plasmin (PLA) in the presence of an activator. Cellular localization assays suggested that the Lsa44 and Lsa45 were surface-exposed. These are versatile proteins capable of interacting with laminin and PLG/PLA, and hence could mediate bacterial adhesion and contribute to tissue penetration.

Evaluation of the immunoprotective effects of IF-2 GTPase and SSU05-1022 as Streptococcus suis candidate subunit vaccine

2021 ◽  
Author(s):  
Tumei Chen ◽  
Chenchen Wang ◽  
Linlin Hu ◽  
Hao Lu ◽  
Fangyu Song ◽  
...  
Keyword(s):  
Recombinant Proteins ◽  
Subunit Vaccine ◽  
Streptococcus Suis ◽  
Cross Protection ◽  
Cytokine Levels ◽  
Antibody Titers ◽  
A Subunit ◽  
Suis Serotype ◽  
Lethal Doses ◽  
Mixed Protein

Aim: This study aims to develop a subunit vaccine with high cross-protection for Streptococcus suis. Materials & methods: Four-week-old female BALB/c mice were first immunized with a single and mixed protein. Various indicators, such as antibody titers and various cytokine levels, were further analyzed. Results: The results showed that purified recombinant proteins IF-2 and 1022 had a good protective effect against lethal doses of S. suis serotype 2 and S. suis serotype 9. This study showed immunization with recombinant proteins. Conclusion: IF-2 and 1022 can enhance cross-protection against S. suis serotypes 2 and 9.

scholarly journals Purification, Stability, and Immunogenicity Analyses of Five Bluetongue Virus Proteins for Use in Development of a Subunit Vaccine That Allows Differentiation of Infected from Vaccinated Animals

2014 ◽  
Vol 21 (3) ◽  
pp. 443-452 ◽  
Author(s):  
Jenna Anderson ◽  
Emmanuel Bréard ◽  
Karin Lövgren Bengtsson ◽  
Kjell-Olov Grönvik ◽  
Stéphan Zientara ◽  
...  
Keyword(s):  
Bluetongue Virus ◽  
Subunit Vaccine ◽  
Clinical Signs ◽  
Igg Antibody ◽  
Content Type ◽  
Vector Borne Diseases ◽  
Antibody Titers ◽  
A Subunit ◽  
Bluetongue Disease ◽  
Vector Borne

ABSTRACTBluetongue virus (BTV) causes bluetongue disease, a vector-borne disease of ruminants. The recent northerly spread of BTV serotype 8 in Europe resulted in outbreaks characterized by clinical signs in cattle, including unusual teratogenic effects. Vaccination has been shown to be crucial for controlling the spread of vector-borne diseases such as BTV. With the aim of developing a novel subunit vaccine targeting BTV-8 that allows differentiation of infected from vaccinated animals, five His-tagged recombinant proteins, VP2 and VP5 of BTV-8 and NS1, NS2, and NS3 of BTV-2, were expressed in baculovirus orEscherichia coliexpression systems for further study. Optimized purification protocols were determined for VP2, NS1, NS2, and NS3, which remained stable for detection for at least 560 to 610 days of storage at +4°C or −80°C, and Western blotting using sera from vaccinated or experimentally infected cattle indicated that VP2 and NS2 were recognized by BTV-specific antibodies. To characterize murine immune responses to the four proteins, mice were subcutaneously immunized twice at a 4-week interval with one of three protein combinations plus immunostimulating complex ISCOM-Matrix adjuvant or with ISCOM-Matrix alone (n= 6 per group). Significantly higher serum IgG antibody titers specific for VP2 and NS2 were detected in immunized mice than were detected in controls. VP2, NS1, and NS2 but not NS3 induced specific lymphocyte proliferative responses upon restimulation of spleen cells from immunized mice. The data suggest that these recombinant purified proteins, VP2, NS1, and NS2, could be an important part of a novel vaccine design against BTV-8.

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