scholarly journals Thermostable Cross-Protective Subunit Vaccine against Brucella Species

2014 ◽  
Vol 21 (12) ◽  
pp. 1681-1688 ◽  
Author(s):  
John W. Cherwonogrodzky ◽  
Nicole D. Barabé ◽  
Michelle L. Grigat ◽  
William E. Lee ◽  
Robert T. Poirier ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Single Injection ◽  
Brucella Melitensis ◽  
Bacterial Colonization ◽  
Brucella Species ◽  
Promising Candidate ◽  
Content Type ◽  
A Subunit ◽  
Multiple Strains

ABSTRACTA subunit vaccine candidate was produced fromBrucella suis145 (biovar 4; expressing both the A antigen ofBrucella abortusand the M antigen ofBrucella melitensis). The preparation consisted mostly of polysaccharide (PS; >90% [wt/wt]; both cell-associated PS and exo-PS were combined) and a small amount of protein (1 to 3%) with no apparent nucleic acids. Vaccinated mice were protected (these had a statistically significant reduction in bacterial colonization compared to that of unvaccinated controls) when challenged with representative strains of threeBrucellaspecies most pathogenic for humans, i.e.,B. abortus,B. melitensis, andB. suis. As little as 1 ng of the vaccine, without added adjuvant, protected mice againstB. suis145 infection (5 × 105CFU), and a single injection of 1 μg of this subunit vaccine protected mice fromB. suis145 challenge for at least 14 months. A single immunization induced a serum IgG response toBrucellaantigens that remained elevated for up to 9 weeks. The use of heat (i.e., boiling-water bath, autoclaving) in the vaccine preparation showed that it was thermostable. This method also ensured safety and security. The vaccine produced was immunogenic and highly protective against multiple strains ofBrucellaand represents a promising candidate for further evaluation.

scholarly journals Evaluation of a subunit vaccine candidate (Biotech Vac Cox) against Eimeria spp. in broiler chickens

2021 ◽  
pp. 101329
Author(s):  
Emanuel Gumina ◽  
Jeffrey W. Hall ◽  
Bruno Vecchi ◽  
Xochitl Hernandez-Velasco ◽  
Brett Lumpkins ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Eimeria Spp ◽  
A Subunit

scholarly journals Cryo-EM structure of S-Trimer, a subunit vaccine candidate for COVID-19

2021 ◽  
Author(s):  
Jiahao Ma ◽  
Danmei Su ◽  
Yinyan Sun ◽  
Xueqin Huang ◽  
Ying Liang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Receptor Binding ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Phase 1 ◽  
Full Length ◽  
Effective Vaccine ◽  
S Protein ◽  
Closed Conformation ◽  
A Subunit

Within a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people worldwide with a death toll over 2 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies. Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. The tightly closed conformation is stabilized by fatty acid and polysorbate 80 binding at the receptor binding domains (RBDs) and the N terminal domains (NTDs) respectively. Additionally, we identified an important pH switch in the WT S-Trimer that shows dramatic conformational change and accounts for its increased stability at lower pH. These results validate Trimer-Tag as a platform technology in production of metastable WT S-Trimer as a candidate for COVID-19 subunit vaccine. IMPORTANCE Effective vaccine against SARS-CoV-2 is critical to end the COVID-19 pandemic. Here, using Trimer-Tag technology, we are able to produce stable and large quantities of WT S-Trimer, a subunit vaccine candidate for COVID-19 with high safety and efficacy from animal and Phase 1 clinical trial studies. Cryo-EM structures of the S-Trimer subunit vaccine candidate show that it predominately adopts tightly closed pre-fusion state, and resembles that of the native and full-length spike in detergent, confirming its structural integrity. WT S-Trimer is currently being evaluated in global Phase 2/3 clinical trial. Combining with published structures of the S protein, we also propose a model to dissect the conformation change of the spike protein before receptor binding.

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

scholarly journals A Heat-Killed Cryptococcus Mutant Strain Induces Host Protection against Multiple Invasive Mycoses in a Murine Vaccine Model

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Yina Wang ◽  
Keyi Wang ◽  
Jorge A. Masso-Silva ◽  
Amariliz Rivera ◽  
Chaoyang Xue
Keyword(s):  
Immune Deficiency ◽  
T Cells ◽  
Fungal Pathogens ◽  
Vaccine Candidate ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Host Immunity ◽  
Content Type ◽  
A Subunit ◽  
F Box Protein

ABSTRACT Cryptococcus neoformans is a fungal pathogen that infects the lungs and then often disseminates to the central nervous system, causing meningitis. How Cryptococcus is able to suppress host immunity and escape the antifungal activity of macrophages remains incompletely understood. We reported that the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase, promotes Cryptococcus virulence by regulating host-Cryptococcus interactions. Our recent studies demonstrated that the fbp1Δ mutant elicited superior protective Th1 host immunity in the lungs and that the enhanced immunogenicity of heat-killed fbp1Δ yeast cells can be harnessed to confer protection against a subsequent infection with the virulent parental strain. We therefore examined the use of heat-killed fbp1Δ cells in several vaccination strategies. Interestingly, the vaccine protection remains effective even in mice depleted of CD4+ T cells. This finding is particularly important in the context of HIV/AIDS-induced immune deficiency. Moreover, we observed that vaccinating mice with heat-killed fbp1Δ induces significant cross-protection against challenge with diverse invasive fungal pathogens, including C. neoformans, C. gattii, and Aspergillus fumigatus, as well as partial protection against Candida albicans. Thus, our data suggest that the heat-killed fbp1Δ strain has the potential to be a suitable vaccine candidate against cryptococcosis and other invasive fungal infections in both immunocompetent and immunocompromised populations. IMPORTANCE Invasive fungal infections kill more than 1.5 million people each year, with limited treatment options. There is no vaccine available in clinical use to prevent and control fungal infections. Our recent studies showed that a mutant of the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase in Cryptococcus neoformans, elicited superior protective Th1 host immunity. Here, we demonstrate that the heat-killed fbp1Δ cells (HK-fbp1) can be harnessed to confer protection against a challenge by the virulent parental strain, even in animals depleted of CD4+ T cells. This finding is particularly important in the context of HIV/AIDS-induced immune deficiency. Moreover, we observed that HK-fbp1 vaccination induces significant cross-protection against challenge with diverse invasive fungal pathogens. Thus, our data suggest that HK-fbp1 has the potential to be a broad-spectrum vaccine candidate against invasive fungal infections in both immunocompetent and immunocompromised populations.

Insights into irr and rirA gene regulation on the virulence of Brucella melitensis M5-90

2020 ◽  
Vol 66 (5) ◽  
pp. 351-358
Author(s):  
Huan Zhang ◽  
Benben Wang ◽  
Wenxing Wu ◽  
Xiaoyu Deng ◽  
Zhiran Shao ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Brucella Abortus ◽  
Vaccine Candidate ◽  
Brucella Melitensis ◽  
Response Regulator ◽  
Iron Acquisition ◽  
Brucella Species ◽  
Splenic Index ◽  
Number Of Bacteria ◽  
Growth Ability

Iron is a fundamental element required by most organisms, including Brucella. Several researchers have suggested that the iron response regulator (irr) and rhizobial iron regulator (rirA) genes regulate iron acquisition by Brucella abortus, influencing heme synthesis by and virulence of this pathogen. However, little is known about another Brucella species, Brucella melitensis. In this research, we successfully constructed two mutants: M5-90Δirr and M5-90ΔrirA. The adhesion, invasion, and intracellular survivability of these two mutants were evaluated in RAW264.7 cells infected with 1 × 106 CFU of M5-90Δirr, M5-90ΔrirA, or M5-90. We also tested the sensitivity of cells to hydrogen peroxide and their ability to grow. In addition, the virulence of these two mutants was evaluated in BALB/c mice. The results showed that the ability of these two mutants to invade and adhere inside the murine macrophages RAW264.7 was attenuated but their ability to replicate intracellularly was strengthened, enhancing the resistance to hydrogen peroxide. The M5-90Δirr mutant showed stronger growth ability than the parental strain under iron-limiting conditions. No differences were observed in the number of bacteria in spleen between M5-90 and M5-90Δirr at 7 or 15 days postinfection. However, the number of M5-90ΔrirA in spleen reduced significantly at 15 days postinfection. The splenic index of the M5-90Δirr group is evidently lower than that of M5-90. This is the first report that irr and rirA genes of B. melitensis are associated not only with virulence but also with growth ability. Together, our data suggest that M5-90Δirr is a promising Brucella vaccine candidate.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document