A5034049607- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- Bacillus and Francisella bacterial research
- Animal Virus Infections Studies
- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Viral gastroenteritis research and epidemiology
- Transgenic Plants and Applications
- Viral Infections and Immunology Research
- Bacteriophages and microbial interactions
- Parasites and Host Interactions
- SARS-CoV-2 detection and testing
- Helminth infection and control
- Insect symbiosis and bacterial influences
- Parasite Biology and Host Interactions
Baylor College of Medicine
2021-2025
Texas Children's Hospital
2020-2025
Center for Children
2021
There is an urgent need for accessible and low-cost COVID-19 vaccine suitable low- middle-income countries. Here, we report on the development of a SARS-CoV-2 receptor-binding domain (RBD) protein, expressed at high levels in yeast (Pichia pastoris), as candidate against COVID-19. After introducing two modifications into wild-type RBD gene to reduce yeast-derived hyperglycosylation improve stability during protein expression, show that recombinant RBD219-N1C1, equivalent (RBD219-WT) vitro...
A SARS-CoV-2 RBD219-N1C1 (RBD219-N1C1) recombinant protein antigen formulated on Alhydrogel® has recently been shown to elicit a robust neutralizing antibody response against pseudovirus in mice. The produced under current good manufacturing practices (cGMPs) and is now clinical testing. Here, we report process development scale-up optimization for upstream fermentation downstream purification of the antigen. This includes production at 1-L 5-L scales yeast, Pichia pastoris, comparison three...
SARS-CoV-2 protein subunit vaccines are currently being evaluated by multiple manufacturers to address the global vaccine equity gap, and need for low-cost, easy scale, safe, effective COVID-19 vaccines. In this paper, we report on generation of receptor-binding domain RBD203-N1 yeast expression construct, which produces a recombinant capable eliciting robust immune response protection in mice against challenge infections. The antigen was expressed Pichia pastoris X33. After fermentation at...
We conducted preclinical studies in mice using a yeast-produced SARS-CoV-2 RBD subunit vaccine candidate formulated with aluminum hydroxide (alum) and CpG deoxynucleotides. This formulation is equivalent to the CorbevaxTM that recently received emergency use authorization by Drugs Controller General of India. compared immune response vaccinated RBD/alum + CpG. also evaluated immunized boosted RBD/alum. Mice were twice intramuscularly at 21-day interval. Compared two doses /alum formulation,...
Introduction The development of a yeast-expressed recombinant protein-based vaccine technology co-developed with LMIC producers and suitable as COVID-19 for global access is described. proof-of-concept developing SARS-CoV-2 spike protein receptor-binding domain (RBD) antigen yeast-derived described.Areas Covered Genetic Engineering: strategy presented the design genetic modification used during cloning expression in yeast system. Process Assay Development: A summary how scalable,...
Chagas disease (CD) (American trypanosomiasis caused by Trypanosoma cruzi) is a parasitic endemic in 21 countries South America, with increasing global spread. When administered late the infection, current antiparasitic drugs do not prevent onset of cardiac illness leading to chronic Chagasic cardiomyopathy. Therefore, new therapeutic vaccines or immunotherapies are under development using multiple platforms. In this study, we assessed feasibility developing an mRNA-based CD vaccine...
Tc24 is a Trypanosoma cruzi-derived flagellar protein that, when formulated with TLR-4 agonist adjuvant, induces balanced immune response in mice, elevating IgG2a antibody titers and IFN-γ levels. Furthermore, vaccination the recombinant can reduce parasite levels improve survival during acute infection. Although some mRNA vaccines have been proven to elicit stronger than vaccines, they not used against T. cruzi. This work evaluates immunogenicity of heterologous prime/boost regimen using...
Background The antigen Na -GST-1, expressed by the hookworm Necator americanus , plays crucial biochemical roles in parasite survival. This study explores development of mRNA vaccine candidates based on building success recombinant -GST-1 (r -GST-1) protein, currently assessed as a subunit candidate, which has shown promise preclinical and clinical studies. Methodology/findings By leveraging flexible design RNA vaccines protein intracellular trafficking signal sequences, we developed three...
Introduction Chagas disease (CD), caused by the parasite Trypanosoma cruzi , affects millions globally. Despite treatment options in acute phase, most infections progress to a chronic indeterminate form or develop severe cardiac/gastrointestinal complications. Understanding immune response is crucial for development of vaccines and more efficient drugs control. Methods This work investigates T. H1 K68 strain infection female BALB/c C57BL/6 mice characterize differences Tfh B cell responses...
Abstract There is an urgent need for accessible and low-cost COVID-19 vaccine suitable low- middle-income countries. Here we report on the development of a SARS-CoV-2 receptor-binding domain (RBD) protein, expressed at high levels in yeast ( Pichia pastoris ), as candidate against COVID-19. After introducing two modifications into wild-type RBD gene to reduce yeast-derived hyperglycosylation improve stability during protein expression, show that recombinant RBD219-N1C1, equivalent...
(1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting receptor-binding domain (RBD) spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice non-human primates, our wild-type (WT) RBD vaccine induced high neutralizing antibody titers against WT isolate virus, and, partners in India Indonesia, it was later developed into two closely resembling human vaccines, Corbevax Indovac. Here, we describe...
Abstract The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses others currently exclusive bats, indicating epitope preservation individual antigens during...
Tc24-C4, a modified recombinant flagellar calcium-binding protein of Trypanosoma cruzi , is under development as therapeutic subunit vaccine candidate to prevent or delay progression chronic Chagasic cardiomyopathy. When combined with Toll-like receptor agonists, Tc24-C4 immunization reduces parasitemia, parasites in cardiac tissue, and fibrosis inflammation animal models. To support further research on the its mechanism action, murine monoclonal antibodies (mAbs) against were generated....
ABSTRACT Background Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has now spread worldwide to infect over 110 million people, with approximately 2.5 reported deaths. A safe and effective vaccine remains urgently needed. Method We constructed three variants of the recombinant receptor-binding domain (RBD) spike (S) protein (residues 331-549) in yeast as follows: (1) a “wild type” RBD (RBD219-WT), (2) deglycosylated form (RBD219-N1) deleting first N-glycosylation site, (3) combined...
We conducted preclinical studies in mice using a yeast-produced SARS-CoV-2 RBD subunit vaccine candidate formulated with aluminum hydroxide (alum) and CpG deoxynucleotides. This formulation is equivalent to the CorbevaxTM that recently received emergency use authorization by Drugs Controller General of India. compared immune response vaccinated RBD/alum RBD/alum+CpG. also evaluated immunized RBD/alum+CpG boosted RBD/alum. Mice were twice intramuscularly at 21-day interval. Compared two doses...
Trypanosoma cruzi is a protozoan parasite that causes Chagas disease. Globally 6 to 7 million people are infected by this of which 20–30% will progress develop Chronic Chagasic Cardiomyopathy (CCC). Despite its high disease burden, no clinically approved vaccine exists for the prevention or treatment CCC. Developing vaccines can stimulate T . -specific CD8+ cytotoxic cells and eliminate requires targeting parasitic antigens presented on major histocompatibility complex-I (MHC-I) molecules....
Abstract A SARS-CoV-2 RBD219-N1C1 (RBD219-N1C1) recombinant protein antigen formulated on Alhydrogel ® has recently been shown to elicit a robust neutralizing antibody response against pseudovirus in mice. The produced under current good manufacturing practices (cGMP) and is now clinical testing. Here, we report process development scale-up optimization for upstream fermentation downstream purification of the antigen. This includes production at 1 5 L scale yeast, Pichia pastoris, comparison...
(1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting Receptor-Binding Domain (RBD) spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice non-human primates, our original RBD vaccine induced high neutralizing antibody titers against wild-type (WT) isolate virus, and, partners in India Indonesia it was later developed into two closely resembling human vaccines, Corbevax Indovac, respectively. Here,...
(1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting Receptor-Binding Domain (RBD) spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice non-human primates, our original RBD vaccine induced high neutralizing antibody titers against wild-type (WT) isolate virus, and, partners in India Indonesia it was later developed into two closely resembling human vaccines, Corbevax Indovac, respectively. Here,...
(1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting Receptor-Binding Domain (RBD) spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice non-human primates, our original RBD vaccine induced high neutralizing antibody titers against wild-type (WT) isolate virus, and, partners in India Indonesia it was later developed into two closely resembling human vaccines, Corbevax Indovac, respectively. Here,...
(1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting Receptor-Binding Domain (RBD) spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice non-human primates, our wild-type (WT) RBD vaccine induced high neutralizing antibody titers against WT isolate virus, and, partners in India Indonesia it was later developed into two closely resembling human vaccines, Corbevax Indovac. Here, we describe...
ABSTRACT Background SARS-CoV-2 protein subunit vaccines are being evaluated by multiple manufacturers to fill the need for low-cost, easy scale, safe, and effective COVID-19 global access. Vaccine candidates relying on receptor-binding domain (RBD) of spike have been focus our development program. In this paper, we report generation RBD203-N1 yeast expression construct, which produces a recombinant that when formulated with alum TLR-9 agonist, CpG1826 elicits robust immune response...