A5062233994- Influenza Virus Research Studies
- Respiratory viral infections research
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- Diabetes and associated disorders
- interferon and immune responses
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Receptor Mechanisms and Signaling
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Metabolomics and Mass Spectrometry Studies
- Long-Term Effects of COVID-19
- COVID-19 Clinical Research Studies
- Advanced Proteomics Techniques and Applications
- Animal Virus Infections Studies
- RNA and protein synthesis mechanisms
- Bacterial Infections and Vaccines
- Biochemical effects in animals
- Viral Infections and Outbreaks Research
- Animal Disease Management and Epidemiology
- Mast cells and histamine
- Tryptophan and brain disorders
- COVID-19 and Mental Health
Cleveland Clinic Florida
2023-2025
University of Georgia
2017-2024
Cleveland Clinic
2023
Multiple sclerosis (MS) is a severe autoimmune disorder that wreaks havoc on the central nervous system, leading to spectrum of motor and cognitive impairments. There no cure, current treatment strategies rely broad immunosuppression, leaving patients vulnerable infections. To address this problem, our approach aims induce antigen-specific tolerance, much-needed shift in MS therapy. We have engineered tolerogenic therapy consisting spray-dried particles made degradable biopolymer, acetalated...
Most humans have pre-existing immunity to influenza viruses. In this study, volunteers (ages of 18-85 years) were vaccinated with split, inactivated Fluzone™ vaccine in four consecutive seasons from 2013 2016 seasons. The impact repeated vaccination on breadth and durability antibodies was assessed as a result strain changes. Total IgG anti-hemagglutinin (HA) binding hemagglutination-inhibition (HAI) activity increased all age groups against both A HA components the post-vaccination (day...
Most preclinical animal studies test influenza vaccines in immunologically naive models, even though the results of vaccination may not accurately reflect effectiveness vaccine candidates humans that have preexisting immunity to influenza. In this study, novel, broadly reactive were assessed preimmune ferrets. These animals infected with different H1N1 isolates before being vaccinated or another virus. Previously, our group has described design and characterization computationally optimized...
Participants between the ages of 10–86 years old were vaccinated with split-inactivated influenza vaccine (Fluzone®) in six consecutive seasons from 2016–2017 to 2021–2022. Vaccine effectiveness varies season as a result both host immune responses well evolutionary changes virus surface glycoproteins that provide challenges manufacturers produce more effective annual vaccines. Next generation vaccines are development and may protective against broader number viruses reduce need for...
Pre-existing immunity to influenza is dependent on a number of factors and can vary greatly within across subtypes. In this study, volunteers (aged 18–85 years) were vaccinated with split, inactivated FluzoneTM in four consecutive seasons from 2013 2016. The impact repeat vaccination breadth durability functional antibodies was assessed for total IgG IgA anti-hemagglutinin (HA) binding hemagglutination-inhibition (HAI) activity against both B lineages. Many subjects able maintain high...
Influenza virus poses an ongoing human health threat with pandemic potential. Due to mutations in circulating strains, formulating effective vaccines remains a challenge. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) proteins is promising vaccine strategy protect against wide range current and future influenza viruses. Though preclinical studies, the mechanistic basis driving broad reactivity COBRA be elucidated. Here, we report crystal structure HA...
Influenza B viruses (IBV) can cause severe disease and death much like influenza A (IAV), with a disproportionate number of infections in children. Despite moving to quadrivalent vaccine include strains from both the B/Victoria B/Yamagata lineages, effectiveness rates continue be variable low many past seasons. To develop more effective virus vaccines, three novel IBV hemagglutinin (HA) vaccines were designed using computationally optimized broadly reactive antigen (COBRA) methodology. These...
A key to improving vaccine design and vaccination strategy is understand the mechanism behind variation of response with host factors. Glycosylation, a critical modulator immunity, has no clear role in determining responses. To gain insight into association between glycosylation vaccine-induced antibody levels, we profiled pre- postvaccination serum protein glycomes 160 Caucasian adults receiving FLUZONE influenza during 2019-2020 season using lectin microarray technology. We found that...
The seasonal influenza vaccine is only effective in half of the vaccinated population. To identify determinants efficacy, we used data from > 1,300 vaccination events to predict response measured as seroconversion well hemagglutination inhibition (HAI) titer levels one year after. We evaluated predictive capabilities age, body mass index (BMI), sex, race, comorbidities, history, and baseline HAI titers, month dose multiple linear regression models. models predicted categorical for 75% cases...
Abstract The COVID-19 pandemic, triggered by severe acute respiratory syndrome coronavirus 2, has affected millions of people worldwide. Much research been dedicated to our understanding disease heterogeneity and severity, but less is known about recovery associated changes. To address this gap in knowledge, we quantified the proteome from serum samples 29 convalescents age-, race-, sex-matched healthy controls. Samples were acquired within first months pandemic. Many proteins pathways...
Currently licensed vaccine adjuvants offer limited mucosal immunity, which is needed to better combat respiratory infections such as influenza. Mast cells (MCs) are emerging a target for new class of adjuvants. Here, we developed and characterized nanoparticulate adjuvant composed an MC activator [mastoparan-7 (M7)] TLR ligand (CpG). This novel nanoparticle (NP) was co-formulated with computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA), against influenza strains. M7...
Abstract Current FDA‐approved influenza vaccines are limited by variable year to efficacy, low immunogenicity, and poor stability outside of cold‐chain storage. Polymeric microparticles can overcome many these issues provide an improved vaccine platform. Here, acetalated dextran microparticle platform is used encapsulate a broadly active COBRA immunogen the adjuvant cGAMP. Microparticles fabricated via highly scalable electrospray method. Mice vaccinated with loaded cGAMP produced antibodies...
Current seasonal influenza vaccines are limited in that they need to be reformulated every year order account for the constant mutation of virus. Hemagglutinin (HA) immunogens have been developed using a computationally optimized broadly reactive antigen (COBRA) methodology, which able elicit an antibody response neutralizes antigenically distinct strains; however, subunit proteins not immunogenic enough on their own generate substantial immune response. Due this, different delivery...
Abstract Influenza viruses infect 5–30% of the world’s population annually, resulting in millions incidents hospitalization and thousands mortalities worldwide every year. Although annual vaccination has significantly reduced rates vulnerable populations, current vaccines are estimated to offer a wide range protection from 10 60% annually. Such incomplete immunity may be related both poor antigenic coverage circulating strains, as well insufficient induction protective immunity. Beyond role...
Better understanding of the molecular mechanisms underlying COVID-19 severity is desperately needed in current times. Although hyper-inflammation drives severe COVID-19, precise triggering this cascade and what role glycosylation might play therein are unknown. Here we report first high-throughput glycomic analysis plasma samples autopsy tissues. We find that α2,6-sialylation upregulated patients with autopsied lung tissue. This glycan motif enriched on members complement (e.g., C5, C9),...
Abstract Influenza virus outbreaks are a major burden worldwide each year. Current vaccination strategies inadequate due to antigenic drift/shift of the and elicitation low immune responses. The use computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) immunogens subvert constantly mutating viruses; however, they poorly immunogenic on their own. To increase immunogenicity subunit vaccines such as this, adjuvants can be delivered with vaccine. For example, agonists...
Seasonal influenza is a primary public health burden in the USA and globally. Annual vaccination programs are designed on basis of circulating viral strains. However, effectiveness seasonal vaccine highly variable between seasons among individuals. A number factors known to influence including age, sex, comorbidities. Here, we sought determine whether whole blood gene expression profiling prior informative about pre-existing immunological status response vaccine. We performed transcriptome...
Influenza represents a major and ongoing public health hazard. Current collaborative efforts are aimed toward creating universal flu vaccine with the goals of both improving responses to vaccination increasing breadth protection against multiple strains clades from single vaccine. As an intermediate step these goals, current work is focused on evaluating systemic host response in normal high-risk populations, such as obese geriatric which have been linked poor vaccination. We therefore...