Gregory D. Gromowski
A5039786822- Mosquito-borne diseases and control
- Viral Infections and Vectors
- SARS-CoV-2 and COVID-19 Research
- Malaria Research and Control
- COVID-19 Clinical Research Studies
- Viral Infections and Outbreaks Research
- Virology and Viral Diseases
- COVID-19 Impact on Reproduction
- Animal Virus Infections Studies
- SARS-CoV-2 detection and testing
- HIV Research and Treatment
- Insect symbiosis and bacterial influences
- Dengue and Mosquito Control Research
- COVID-19 epidemiological studies
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- Monoclonal and Polyclonal Antibodies Research
- Complement system in diseases
- T-cell and B-cell Immunology
- GaN-based semiconductor devices and materials
- vaccines and immunoinformatics approaches
- Toxin Mechanisms and Immunotoxins
- Transgenic Plants and Applications
- Vector-borne infectious diseases
- Zoonotic diseases and public health
Walter Reed Army Institute of Research
2017-2024
University of Maryland, Baltimore
2023
SUNY Upstate Medical University
2023
University of Maryland, College Park
2023
Henry M. Jackson Foundation
2022
Makerere University Walter Reed Project
2022
The University of Texas Medical Branch at Galveston
2005-2017
National Institute of Allergy and Infectious Diseases
2014-2015
National Institutes of Health
2014-2015
The devil in the dengue details Along with their mosquito vectors, viruses are spreading worldwide to infect millions of people. For a few, subsequent infection results lethal hemorrhagic disease. Katzelnick et al. used antibody-binding data map structural divergence and antigenic variation among viruses. Comparing monkeys humans, approximately clustered into four known groups. However, virus groups showed as much distance within group between This finding helps explain why immune responses...
The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants concern (VoCs) and long-term threat emerging coronaviruses. Here, we design characterize four categories engineered nanoparticle immunogens that recapitulate structural antigenic properties prefusion SARS-CoV-2 spike (S), S1, receptor-binding domain (RBD). These induce robust S binding, ACE2 inhibition, authentic pseudovirus neutralizing antibodies...
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against disease 2019. We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50-μg) SpFN vaccine, given twice 28 days apart, induced a T helper cell 1 (T H 1)–biased CD4 response elicited neutralizing antibodies wild type concern, as well SARS-CoV-1....
Abstract Dengue is a major health threat and the number of symptomatic infections caused by four dengue serotypes estimated to be 96 million 1 with annually around 10,000 deaths 2 . However, no antiviral drugs are available for treatment or prophylaxis dengue. We recently described interaction between non-structural proteins NS3 NS4B as promising target development pan-serotype virus (DENV) inhibitors 3 Here we present JNJ-1802—a highly potent DENV inhibitor that blocks NS3–NS4B within viral...
The introduction of West Nile virus (WNV) into North America has been associated with relatively high rates neurological disease and death in humans, birds, horses, some other animals. Previous studies identified strains both genetic lineage 1 2, including American isolates 1, that were highly virulent a mouse neuroinvasion model, while avirulent or significantly attenuated (D. W. C. Beasley, L. Li, M. T. Suderman, A. D. Barrett, Virology 296:17-23, 2002). To begin to elucidate the basis for...
ABSTRACT Neutralization of flaviviruses in vivo correlates with the development an antibody response against viral envelope (E) protein. Previous studies demonstrated that monoclonal antibodies (MAbs) epitope on lateral ridge domain III (DIII) West Nile virus (WNV) E protein strongly protect infection animals. Based X-ray crystallography and sequence analysis, analogous type-specific neutralizing for individual serotypes related flavivirus dengue (DENV) was hypothesized. Using yeast surface...
ABSTRACT The surface of the mature dengue virus (DENV) particle is covered with 180 envelope (E) proteins arranged as homodimers that lie relatively flat on virion surface. Each monomer consists three domains (ED1, ED2, and ED3), which ED3 contains critical neutralization determinant(s). In this study, a large panel DENV-2 recombinant mutant was used to physically biologically map epitopes five DENV complex-specific monoclonal antibodies (MAbs). All MAbs recognized single antigenic site...
Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika (ZIKV), promoting increased ZIKV infection vitro. However, the correlation between vitro and vivo findings is not well characterized. Thus, we evaluated impact heterotypic flavivirus immunity on titers biofluids rhesus macaques. Animals previously infected (≥420 days) with DENV2, DENV4, or yellow fever were compared to flavivirus-naïve animals following a Brazilian strain. Sera from...
Not all vaccines afford robust protection against ZIKV challenge in rhesus monkeys at 1 year after vaccination.
Infection with one of dengue viruses 1 to 4 (DENV1-4) induces protective antibodies against homotypic infection. However, a notable feature is the ability use preexisting heterotypic infect Fcγ receptor–bearing immune cells, leading higher viral load and immunopathological events that augment disease. We tracked antigenic dynamics each DENV serotype by using 1944 sequenced isolates from Bangkok, Thailand, between 1994 2014 (348 strains), in comparison regional global diversity (64 strains)....
Abstract The emergence of SARS-CoV-2 variants concern (VOC) requires adequate coverage vaccine protection. We evaluated whether a spike ferritin nanoparticle (SpFN), adjuvanted with the Army Liposomal Formulation QS21 (ALFQ), conferred protection against Alpha (B.1.1.7), and Beta (B.1.351) VOCs in Syrian golden hamsters. SpFN-ALFQ was administered as either single or double-vaccination (0 4 week) regimens, using high (10 μg) low (0.2 dose. Animals were intranasally challenged at week 11....
Emergence of novel variants the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores need for next-generation vaccines able to elicit broad and durable immunity. Here we report evaluation a ferritin nanoparticle vaccine displaying receptor-binding domain SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination macaques using two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses reciprocal peak mean...
Despite rapid and ongoing vaccine therapeutic development, SARS-CoV-2 continues to evolve evade, presenting a need for next-generation diverse modalities. Here we show that nurse sharks immunized with recombinant receptor binding domain (RBD), RBD-ferritin (RFN), or spike protein ferritin nanoparticle (SpFN) immunogens elicit set of new antigen antibody (IgNAR) molecules target two non-overlapping conserved epitopes on the RBD. Representative shark variable NAR-Fc chimeras (ShAbs) targeting...
Abstract The repeat emergence of SARS-CoV-2 variants concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need develop next-generation vaccine candidates that confer broad protection. Here we describe antibody response induced by Spike Ferritin Nanoparticle (SpFN) candidate adjuvanted Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal directed against Receptor Binding Domain (RBD),...
Zika virus (ZIKV) is a mosquito-borne member of the genus Flavivirus that has emerged since 2007 to cause outbreaks in Africa, Asia, Oceania, and most recently, Americas. Here, we used an isolate history as well genetic phylogenetic analyses characterize three low-passage isolates representing African (ArD 41525) Asian (CPC-0740, SV0127-14) lineages investigate potential phenotypic differences vitro vivo. The displayed large plaque phenotype (∼3-4 mm) on Vero HEK-293 cells, whereas either...
Prevention of viral escape and increased coverage against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concern require therapeutic monoclonal antibodies (mAbs) targeting multiple sites vulnerability on the spike glycoprotein. Here we identify several potent neutralizing directed either N-terminal domain (NTD) or receptor-binding (RBD) protein. Administered in combinations, these mAbs provided low-dose protection SARS-CoV-2 infection K18-human angiotensin-converting...
Characterization of MAbs against SARS-CoV-2, elicited through vaccination or natural infection, has provided vital immunotherapeutic options for curbing the COVID-19 pandemic and supplied critical insights into SARS-CoV-2 escape, transmissibility, mechanisms viral inactivation. Neutralizing that target RBD but do not block ACE2 binding are particular interest because epitopes well conserved within sarbecoviruses targeting this area demonstrate cross-reactivity.
ABSTRACT The safety and efficacy of the live-attenuated Japanese encephalitis virus (JEV) SA14-14-2 vaccine are attributed to mutations that accumulated in viral genome during its derivation. However, little is known about contribution made by most these virulence attenuation immunogenicity. Here, we generated recombinant JEV (rJEV) strains containing vaccine-specific located untranslated regions (UTRs) seven protein genes or introduced from PCR-amplified genome. resulting mutant viruses...
A stabilized dimer of the surface protein from dengue virus has been engineered to elicit antibodies that neutralize virus.
The COVID-19 pandemic has had a staggering impact on social, economic, and public health systems worldwide. Vaccine development mobilization against SARS-CoV-2 (the etiologic agent of COVID-19) been rapid. However, novel strategies are still necessary to slow the pandemic, this includes new approaches vaccine and/or delivery that will improve vaccination compliance demonstrate efficacy emerging variants. Here, we report immunogenicity comprising stabilized, pre-fusion spike protein trimers...
Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants concern (VoCs), immunotherapeutics that target conserved epitopes on spike (S) glycoprotein have therapeutic advantages. Here, we report crystal structure SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility distinct conformations angiotensin-converting enzyme (ACE2)-binding site. We identify a set SARS-CoV-2-reactive monoclonal antibodies (mAbs) with broad RBD...