Lindsay Wieczorek
A5055341298- HIV Research and Treatment
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- HIV/AIDS drug development and treatment
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- Herpesvirus Infections and Treatments
- HIV/AIDS Research and Interventions
- SARS-CoV-2 detection and testing
- Animal Virus Infections Studies
- COVID-19 Clinical Research Studies
- Hepatitis C virus research
- Bacteriophages and microbial interactions
- Blood groups and transfusion
- Cytomegalovirus and herpesvirus research
- COVID-19 Impact on Reproduction
- Viral Infections and Outbreaks Research
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Mosquito-borne diseases and control
- Virology and Viral Diseases
- Hepatitis B Virus Studies
- Viral Infections and Immunology Research
Henry M. Jackson Foundation
2014-2024
Walter Reed Army Institute of Research
2014-2024
University of America
2020
Catholic University of America
2020
University of Pennsylvania
2016
The Wistar Institute
2016
Jackson Foundation
2008-2016
Indiana University School of Medicine
2015
University of Wisconsin–Madison
2004
Friedrich-Alexander-Universität Erlangen-Nürnberg
1992
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...
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....
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),...
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.
To augment HIV-1 pox-protein vaccine immunogenicity using a next generation adjuvant, prime-boost strategy of recombinant modified vaccinia virus Ankara and multimeric Env gp145 was evaluated in macaques with either aluminum (alum) or novel liposomal monophosphoryl lipid A (MPLA) formulation adsorbed to alum, ALFA. Binding antibody responses were robust comparable between arms, while antibody-dependent neutrophil monocyte phagocytotic greatly enhanced by Per-exposure efficacy against...
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...
Objectives: There is a need to develop HIV-1 vaccine formulations that incorporate inexpensive antigens and clinically acceptable potent adjuvants for inducing neutralizing antibodies. The purpose of this initial study was produce peptide- lipid-induced murine mAbs replicate the characteristics 2F5 and/or 4E10 human antibodies in binding both membrane proximal external region (MPER) glycoprotein 41 adjacent lipid bilayer infection CD4+ lymphocytes. Research designs methods: Liposomes...
Although CD4(+) cells represent the major target for HIV infection in blood, claims of complement-independent binding HIV-1 to erythrocytes and possible role Duffy blood group antigen, have generated controversy. To examine question erythrocytes, was incubated vitro with from 30 healthy leukapheresis donors, determined by p24 analysis adsorption reduction infectivity cells. All cells, regardless type, bound p24. A typical preparation <2.4% added p24, but selectively removed essentially all...
ABSTRACT Eliciting broadly reactive functional antibodies remains a challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development that is complicated by variations envelope (Env) subtype and structure. The majority of new global HIV-1 infections are C, novel antigenic properties have been described for C Env proteins. Thus, an protein (CO6980v0c22) from infected person the acute phase (Fiebig stage I/II) was developed as research reagent candidate immunogen. gp145 immunogen...
Background The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. currently available anthrax vaccine requires lengthy immunization schedule, and simpler more immunogenic options for protection against are priority development. In this report we describe phase I clinical trial testing the safety immunogenicity of an using recombinant Escherichia coli-derived, B. protective antigen (rPA). Methodology/Principal Findings A total 73 healthy adults ages 18–40...
Sensitive assays are needed to meaningfully assess low levels of neutralizing antibodies (NAbs) that may be important for protection against the acquisition HIV-1 infection in vaccine recipients. The current assay choice uses a non-lymphoid cell line (TZM-bl) lack sensitivity owing over expression CD4 and CCR5. We used transfection human CD4+/CXCR4+/α4β7+ T-lymphoblastoid (A3.01) with CMV IE promoter-driven CCR5neo vector stably express resulting line, designated A3R5, is permissive wide...
We have previously shown that an HIV vaccine regimen including three HIV-DNA immunizations and a single HIV-modified vaccinia virus Ankara (MVA) boost was safe highly immunogenic in Swedish volunteers. A median 38 months after the first HIV-MVA vaccination, 24 volunteers received 10(8) plaque-forming units of HIV-MVA. The well tolerated. Two weeks this 18 (82%) 22 evaluable vaccinees were interferon (IFN)-γ enzyme-linked immunospot (ELISpot) reactive: to Gag 10 (45%) Env. minimal epitope...
An effective HIV-1 vaccine must elicit broadly neutralizing antibodies (bnAbs) against highly diverse Envelope glycoproteins (Env). Since Env with the longest hypervariable (HV) loops is more resistant to cognate bnAbs than shorter HV loops, we redesigned for updated consensus sequences of subtypes B and C CRF01_AE. Using modeling AlphaFold2, reduced length V1, V2, V5 while maintaining integrity structure glycan shield, modified V4 loop. Spacers are designed limit strain-specific targeting....
SUMMARY The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants concern (VoC) and long-term threat other coronaviruses. Here, we designed characterized four categories engineered nanoparticle immunogens that recapitulate structural antigenic properties prefusion Spike (S), S1 RBD. These induced robust S-binding, ACE2-inhibition, authentic pseudovirus neutralizing antibodies against in mice. A Spike-ferritin (SpFN) vaccine elicited titers more than...
We report the first-in-human safety and immunogenicity evaluation of PENNVAX-G DNA/modified vaccinia Ankara–Chiang Mai double recombinant (MVA-CMDR) prime-boost human immuonodeficiency virus (HIV) vaccine, with intramuscular DNA delivery by either Biojector 2000 needle-free injection system (Biojector) or CELLECTRA electroporation device. Healthy, HIV-uninfected adults were randomized to receive 4 mg delivered intramuscularly at baseline week followed 108 plaque forming units MVA-CMDR weeks...
Fc-mediated virus entry has been observed for many viruses, but the characterization of this activity in convalescent plasma against SARS-CoV-2 Variants Concern (VOC) is undefined. In study, we evaluated viral (FVE) on FcγRIIa-expressing HEK293 cells presence and compared it with pseudovirus neutralization using ACE2-expressing cells. The were collected early pandemic from 39 individuals. We both FVE infecting Washington strain 31% plasmas, neutralization, not 61% no or 8% plasmas....