A5079795098- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Respiratory viral infections research
- Influenza Virus Research Studies
- Biochemical and Molecular Research
- Herpesvirus Infections and Treatments
- SARS-CoV-2 and COVID-19 Research
- Poxvirus research and outbreaks
- Viral gastroenteritis research and epidemiology
- Animal Virus Infections Studies
- Geological formations and processes
- Paleontology and Stratigraphy of Fossils
- Virology and Viral Diseases
- Immunotherapy and Immune Responses
- Hydrocarbon exploration and reservoir analysis
- vaccines and immunoinformatics approaches
- Geochemistry and Geologic Mapping
- CRISPR and Genetic Engineering
- Evolution and Genetic Dynamics
- Immune Cell Function and Interaction
- Transgenic Plants and Applications
- Monoclonal and Polyclonal Antibodies Research
- Synthesis of Tetrazole Derivatives
- COVID-19 Clinical Research Studies
- interferon and immune responses
Ministry of Energy
2023
Merck & Co., Inc., Rahway, NJ, USA (United States)
2015-2022
United States Military Academy
2008-2019
Western University
2012-2013
University of Michigan
2004-2005
Queen's University Belfast
1914
Royal Navy
1914
The RSV Fusion (F) protein is a target for neutralizing antibody responses and focus vaccine discovery; however, the process of entry requires F to adopt metastable prefusion form transition more stable postfusion form, which displays less potent epitopes. mRNA vaccines encode antigens that are translated by host cells following vaccination, may allow conformational transitions similar those observed during natural infection occur. Here we evaluate panel chemically modified expressing...
Significance Hemagglutinin (HA), the major influenza virus envelope glycoprotein, is principal target of neutralizing antibodies. Wide diversity and variation HA entails annual vaccination, as current vaccines typically fail to elicit/boost cross-reactive, broadly antibodies (bnAbs). Although several bnAbs bind at conserved stem making it an attractive universal vaccine candidate, metastable conformation this domain imposes challenges in designing a stable, independently folding immunogen....
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been shown to be a key component of highly active antiretroviral therapy (HAART). The use NNRTIs has become part standard combination antiviral therapies producing clinical outcomes with efficacy comparable other regimens. There is, however, critical issue the emergence resistance, and need arisen for novel broad spectrum activity against HIV-1 RT mutations. Using traditional medicinal chemistry/SAR analyses, crystallography,...
Attempts to develop a vaccine prevent genital herpes simplex virus 2 (HSV-2) disease have been only marginally successful, suggesting that novel strategies are needed. Immunization with HSV-2 glycoprotein C (gC-2) and gD-2 was evaluated in mice guinea pigs determine whether adding gC-2 subunit would improve protection by producing antibodies block immune evasion from complement. Antibodies produced immunization blocked the interaction between complement C3b, passive transfer of antibody...
A herpes simplex virus 2 (HSV-2) glycoprotein E deletion mutant (gE2-del virus) was evaluated as a replication-competent, attenuated live vaccine candidate. The gE2-del is defective in epithelial cell-to-axon spread and anterograde transport from the neuron cell body to axon terminus. In BALB/c SCID mice, caused no death or disease after vaginal, intravascular, intramuscular inoculation 5 orders of magnitude less virulent than wild-type when inoculated directly into brain. No infectious...
A prophylactic vaccine for genital herpes disease remains an elusive goal. We report the results of two studies performed collaboratively in different laboratories that assessed immunogenicity and efficacy simplex virus 1 (HSV-1)-seropositive guinea pigs immunized subsequently challenged intravaginally with HSV-2. In study 1, HSV-2 glycoproteins C (gC2) D (gD2) were produced baculovirus administered intramuscularly as monovalent or bivalent vaccines CpG alum. 2, gD2 was CHO cells given...
Chikungunya virus-like particles (VLPs) have potential to be used as a prophylactic vaccine based on testing in multiple animal models and are currently being evaluated for human use Phase I clinical trial. The current method producing these enveloped alphavirus VLPs by transient gene expression mammalian cells presents challenges scalable robust industrial manufacturing, so the insect cell baculovirus vector system was an alternative technology. Subsequent recombinant infection of Sf21...
Seasonal epidemics caused by influenza A (H1 and H3 subtypes) B viruses are a major global health threat. The traditional, trivalent vaccines have limited efficacy because of rapid antigenic evolution the circulating viruses. This variability mediates viral escape from host immune responses, necessitating annual vaccine updates. Influenza elicit protective antibody response, primarily targeting surface glycoprotein hemagglutinin (HA). However, predominant humoral response is against...
Highly active antiretroviral therapy (HAART) significantly reduces human immunodeficiency virus (HIV) viral load and has led to a dramatic decrease in acquired syndrome (AIDS) related mortality. Despite this success, there remains critical need for new HIV therapies address the emergence of drug resistant strains. Next generation NNRTIs are sought that effective against these mutant forms virus. The bound conformations our lead inhibitors, MK-1107 (1) MK-4965 (2), were divergent about...
Infection with Respiratory Syncytial Virus (RSV) causes both upper and lower respiratory tract disease in humans, leading to significant morbidity mortality young children older adults. Currently, there is no licensed vaccine available, therapeutic options are limited. During the infection process, type I viral fusion (F) glycoprotein on surface of RSV particle rearranges from a metastable prefusion conformation highly stable postfusion form. In people naturally infected RSV, most potent...
Retroviral genomes consist of two unspliced RNAs linked noncovalently in a dimer. Although these are generally identical, different can be copackaged when virions produced by coinfected cells. It has been assumed, but not tested, that copackaging results from random RNA associations the cytoplasm to yield encapsidated homodimers and heterodimers Hardy-Weinberg proportions. Here, virion homo- heterodimerization were examined for Moloney murine leukemia virus (MLV) using nondenaturing Northern...
Biaryl ethers were recently reported as potent NNRTIs. Herein we disclose a detailed SAR study that led to the biaryl ether 6. This compound possessed excellent potency against WT RT and key clinically observed mutants had an pharmacokinetic profile in rats, dogs, rhesus macaques. The also exhibited clean safety preclinical studies.
The prophylactic efficacies of several multivalent replication-incompetent adenovirus serotype 5 (Ad5) vaccines were examined in rhesus macaques using an intrarectal high-dose simian immunodeficiency virus SIVmac239 challenge model. Cohorts Mamu-A*01(+)/B*17(-) Indian immunized with one combinations Ad5 vectors expressing Gag, Pol, Nef, and Env gp140; for comparison, a Mamu-A*01(+) cohort was the vector alone. There no sign immunological interference between antigens animals. In general,...
Abstract Chlamydial major outer membrane protein (MOMP) is the constituent of bacterial pathogen Chlamydia trachomatis. trachomatis Serovars D–K are leading cause genital tract infections which can lead to infertility or ectopic pregnancies. A vaccine against highly desirable but currently not available. MOMP accounts for ~ 60% chlamydial mass and considered be one candidates C. . We report on spectroscopic analysis native D, E, F, J as well muridarum by size exclusion chromatography multi...
One approach to protect new-borns against respiratory syncytial virus (RSV) is vaccinate pregnant women in the last trimester of pregnancy. The boosting circulating antibodies which can be transferred foetus would offer immune protection and ultimately disease. Since non-human primates (NHPs) have similar reproductive anatomy, physiology, antibody architecture kinetics humans, we utilized this preclinical species evaluate maternal immunization (MI) using an RSV F subunit vaccine. Three NHPs...
The surface glycoprotein hemagglutinin (HA) of influenza virus is the primary target for design an effective universal vaccine as it capable eliciting broadly cross-reactive antibodies against different HA subtypes. Several monoclonal targeting stem region that are able to neutralize various subtypes have been isolated in recent past. Designing a stable, immunogen attains native-like conformation and can elicit such has challenge. We describe affinity maturation previously designed (H1HA6)...