Browsing by Author "Chen, Yi-Lin"

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    A Recombinant Protein XBB.1.5 RBD/Alum/CpG Vaccine Elicits High Neutralizing Antibody Titers against Omicron Subvariants of SARS-CoV-2
    (2023) Thimmiraju, Syamala Rani; Adhikari, Rakesh; Villar, Maria Jose; Lee, Jungsoon; Liu, Zhuyun; Kundu, Rakhi; Chen, Yi-Lin; Sharma, Suman; Ghei, Karm; Keegan, Brian; Versteeg, Leroy; Gillespie, Portia M.; Ciciriello, Allan; Islam, Nelufa Y.; Poveda, Cristina; Uzcategui, Nestor; Chen, Wen-Hsiang; Kimata, Jason T.; Zhan, Bin; Strych, Ulrich; Bottazzi, Maria Elena; Hotez, Peter J.; Pollet, Jeroen
    (1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice and non-human primates, our wild-type (WT) RBD vaccine induced high neutralizing antibody titers against the WT isolate of the virus, and, with partners in India and Indonesia, it was later developed into two closely resembling human vaccines, Corbevax and Indovac. Here, we describe the development and characterization of a next-generation vaccine adapted to the recently emerging XBB variants of SARS-CoV-2. (2) Methods: We conducted preclinical studies in mice using a novel yeast-produced SARS-CoV-2 XBB.1.5 RBD subunit vaccine candidate formulated with alum and CpG. We examined the neutralization profile of sera obtained from mice vaccinated twice intramuscularly at a 21-day interval with the XBB.1.5-based RBD vaccine, against WT, Beta, Delta, BA.4, BQ.1.1, BA.2.75.2, XBB.1.16, XBB.1.5, and EG.5.1 SARS-CoV-2 pseudoviruses. (3) Results: The XBB.1.5 RBD/CpG/alum vaccine elicited a robust antibody response in mice. Furthermore, the serum from vaccinated mice demonstrated potent neutralization against the XBB.1.5 pseudovirus as well as several other Omicron pseudoviruses. However, regardless of the high antibody cross-reactivity with ELISA, the anti-XBB.1.5 RBD antigen serum showed low neutralizing titers against the WT and Delta virus variants. (4) Conclusions: Whereas we observed modest cross-neutralization against Omicron subvariants with the sera from mice vaccinated with the WT RBD/CpG/Alum vaccine or with the BA.4/5-based vaccine, the sera raised against the XBB.1.5 RBD showed robust cross-neutralization. These findings underscore the imminent opportunity for an updated vaccine formulation utilizing the XBB.1.5 RBD antigen.
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    A trivalent protein-based pan-Betacoronavirus vaccine elicits cross-neutralizing antibodies against a panel of coronavirus pseudoviruses
    (Springer Nature, 2024) Thimmiraju, Syamala Rani; Adhikari, Rakesh; Redd, JeAnna R.; Villar, Maria Jose; Lee, Jungsoon; Liu, Zhuyun; Chen, Yi-Lin; Sharma, Suman; Kaur, Amandeep; Uzcategui, Nestor L.; Ronca, Shannon E.; Chen, Wen-Hsiang; Kimata, Jason T.; Zhan, Bin; Strych, Ulrich; Bottazzi, Maria Elena; Hotez, Peter J.; Pollet, Jeroen
    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 of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening.
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    Characterization of switchable surfactant interactions with biomimetic surfaces
    (2021-03-16) Chen, Yi-Lin; Biswal, Sibani Lisa
    Amphiphiles are molecules that have both hydrophobic and hydrophilic chemical groups. Common examples of amphiphiles are surfactants, phospholipids, and block copolymers. Due to their dual chemical nature, amphiphiles readily partition to surfaces and interfaces. In the bulk phase, amphiphiles assemble into complex morphologies, such as micelles, vesicles, and lamella structures, to reduce the system free energy. They are widely utilized in different industries such as consumer products, detergents, pharmaceutical drug delivery agents, food science, and oil recovery. Several interfacial interactions have been studied, including amphiphile adsorption or desorption onto substrates, and amphiphile-amphiphile interactions. Recently, switchable surfactants have been reported as an interesting class of amphiphiles that could change their chemical or physical properties when triggered by stimuli, such as pH or light. These are utilized in a variety of applications such as cargo delivery and release and as viscoelastic rheological fluids. However, the underlying mechanism of the behavior of switchable surfactants with surfaces and interfaces remains unclear. Thus, this dissertation systematically investigates how switchable surfactants interact with interfaces by utilizing different surface characterization techniques, including quartz crystal microbalance with dissipation (QCM-D), zeta potential measurements and surface tension measurements. First, the interaction between the switchable surfactant, DTTM (N,N,N' trimethyl-N'-tallow-1,3- diaminopropane), and a silica substrate is investigated. Our results showed that the adsorption is the function of ionic strength and pH of the solution. A two-step adsorption model was applied to characterize DTTM adsorption when above its critical micelle concentration (CMC) while a Langmuir model was used to describe the adsorption when its concentration is below CMC. Next, another switchable surfactant, MSDH (O-methyl-serine dodecylamide hydrochloride), and its interaction with a biomimetic phospholipid membrane, is studied. Two morphologies of phospholipid membrane, liposomes and supported lipid bilayers, were used to understand the governing interactions between MSDH and lipid membranes. Our results suggest that the underlying mechanism for membrane lysis by MSDH differs from the commonly described three-step model used to describe membrane lysis by amphiphiles. Lastly, surface characterization platforms developed for these switchable surfactants are applied to study the interaction between exosomes and lipid bilayers. Exosomes are cell-derived vesicles, which contain protein, RNA, as well as other genetic material, and have been considered to assist with intracellular communication and cargo delivery. However, an understanding of how exosomes pass through the cell membrane remains unclear. From our characterization platform, our results suggest new insights into how cells uptake exosomes. When combined, this thesis provides a systematic platform to study the interactions between complex amphiphiles and interfaces. This dissertation also provides new insights and models to explain how solution conditions alter the interactions of switchable surfactants with interfaces.
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    Two-Step Adsorption of a Switchable Tertiary Amine Surfactant Measured Using a Quartz Crystal Microbalance with Dissipation
    (American Chemical Society, 2019) Chen, Yi-Lin; Zhang, Leilei; Song, Jin; Jian, Guoqing; Hirasaki, George; Johnston, Keith; Biswal, Sibani Lisa
    The adsorption of a switchable cationic surfactant, N,N,N′-trimethyl-N′-tallow-1,3-diaminopropane (DTTM, Duomeen TTM), at the silica/aqueous solution interface is characterized using a quartz crystal microbalance with dissipation (QCM-D). The adsorption isotherms reveal that changes in the solution pH or salinity affect surfactant adsorption in competing ways. In particular, the combination of the degree of protonation of the surfactant and electrostatic interactions is responsible for surfactant adsorption. The kinetics of adsorption is carefully measured using the real-time measurement of a QCM-D, allowing us to fit the experimental data with analytical models. At pH values of 3 and 5, where the DTTM is protonated, DTTM exhibits two-step adsorption. This is representative of a fast step in which the surfactant molecules are adsorbed with head-groups orientated toward the surface, followed by a slower second step corresponding to formation of interfacial surfactant aggregates on the silica surface.