A5076380897- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Neuropeptides and Animal Physiology
- HIV/AIDS drug development and treatment
- Malaria Research and Control
- Mosquito-borne diseases and control
- Bacteriophages and microbial interactions
- Viral-associated cancers and disorders
- X-ray Diffraction in Crystallography
- HIV-related health complications and treatments
- vaccines and immunoinformatics approaches
- Forensic Toxicology and Drug Analysis
- Crystallization and Solubility Studies
- Cytomegalovirus and herpesvirus research
- Lipid Membrane Structure and Behavior
- Immune Cell Function and Interaction
- HIV/AIDS Research and Interventions
- Lymphoma Diagnosis and Treatment
- Opioid Use Disorder Treatment
- Influenza Virus Research Studies
- Pharmacological Receptor Mechanisms and Effects
- Salmonella and Campylobacter epidemiology
- Parvovirus B19 Infection Studies
Walter Reed Army Institute of Research
2014-2025
Henry M. Jackson Foundation
2013-2022
Pfizer (United States)
2021-2022
Government of the United States of America
2021
Jackson Foundation
2006-2021
HJF Medical Research International
2012
University of Debrecen
1999-2009
European Society for Medical Oncology
2005
Centar za Promociju Nauke
2005
Scripps Research Institute
2002
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 development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be potent mode immunization against infectious diseases preclinical studies, and are being tested for SARS-CoV-2 humans. A critical question is how mRNA-LNP immunogenicity compares that traditional adjuvanted protein vaccines primates. Here, we show compared elicits either the same or superior magnitude breadth HIV-1 Env-specific...
Background: The RV144 trial in Thailand is the only HIV-1 vaccine efficacy to date demonstrate any efficacy. Genetic signatures suggested that antibodies targeting variable loop 2 (V2) of envelope played an important protective role. ALVAC prime and protein boost follow-up southern Africa (HVTN702) failed show One hypothesis for this greater diversity subtype C viruses relative CRF01_AE Thailand. Methods: Here, we determined whether with computationally selected gp120 immunogens maximizing...
An improved synthesis of a haptenic heroin surrogate 1 (6-AmHap) is reported. The intermediate needed for the preparation was described in route 2 (DiAmHap). A scalable procedure developed to install C-3 amido group. Using Boc protectng group 18 allowed an overall yield 53% from 4 and eliminated necessity preparing diamide 13. Hapten conjugated tetanus toxoid mixed with liposomes containing monophosphoryl lipid as adjuvant. vaccine induced high anti-1 IgG levels that reduced heroin-induced...
Vaccines against drugs of abuse have induced antibodies in animals that blocked the biological effects drug by sequestering blood and preventing it from crossing blood-brain barrier. Drugs are too small to induce and, therefore, require conjugation hapten analogs a carrier protein. The efficacy these conjugate vaccines depends on several factors including design, coupling strategy, density, protein selection, vaccine adjuvant. Previously, we shown 1 (MorHap), heroin/morphine hapten,...
Malaria caused by Plasmodium falciparum continues to threaten millions of people living in the tropical parts world. A vaccine that confers sterile and life-long protection remains elusive despite more than 30 years effort resources invested solving this problem. Antibodies a malaria candidate circumsporozoite protein (CSP) can block invasion protect humans against malaria. We have manufactured Falciparum Protein-013 (FMP013) based on nearly full-length P. CSP 3D7 strain sequence. report...
We have developed FMP014, a vaccine candidate against Plasmodium falciparum malaria, which is comprised of 60 identical monomer protein chains that form an icosahedral shaped self-assembling nanoparticle (SAPN). Each contains selected P. Circumsporozoite Protein (PfCSP) CD4+ and CD8+ epitopes, universal TH portions the α-TSR domain, 6 repeats NANP motifs PfCSP. Here we describe conditions are required for successful scale-up cGMP manufacturing FMP014 with yield ≈1.5 g drug substance per 100...
Aluminum salts have been used as vaccine adjuvants for >50 years, and they are currently present in at least 146 licensed vaccines worldwide. In this study we examined whether adsorption of Army Liposome Formulation (ALF) to an aluminum salt that already has antigen adsorbed it might result improved immune potency the aluminum-adsorbed antigen. ALF is composed a family anionic liposome-based adjuvants, which liposomes contain synthetic phospholipids having dimyristoyl fatty acyl groups,...
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...
Survivin has recently been identified as a novel member of the inhibitor apoptosis (IAP) gene family. The product this not only suppresses but also controls cell division. is undetectable in most terminally differentiated normal tissues expressed embryonic and fetal organs present malignant tumours. Human papillomaviruses (HPV) are thought to play an important role development cervical cancer. By interfering cycle, viral oncoproteins (E6 E7) can induce immortalization host cell....
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...
Antibodies to Circumsporozoite protein (CSP) confer protection against controlled human malaria infection (CHMI) caused by the parasite Plasmodium falciparum. Although CSP is highly immunogenic, it does not induce long lasting and efforts improve CSP-specific immunological memory duration of are underway. We have previously reported that clinical grade vaccine FMP013 was immunogenic protective challenge in mice when combined with Army Liposomal Formulation adjuvant containing immune...
Active immunization is an emerging potential modality to combat fatal overdose amid the opioid epidemic. In this study, we described design, synthesis, formulation, and animal testing of efficacious vaccine against fentanyl. The formulation composed a novel fentanyl hapten conjugated tetanus toxoid (TT) adjuvanted with liposomes containing monophosphoryl lipid A adsorbed on aluminum hydroxide. linker N-phenyl-N-(1-(4-(3-(tritylthio)propanamido)phenethyl)piperidin-4-yl)propionamide were...
ABSTRACT Both a murine monoclonal antibody to phosphatidylinositol phosphate (PIP) and human (4E10) that is known have broadly neutralizing capabilities against primary isolates of immunodeficiency virus type 1 (HIV-1) bound PIP, as determined by enzyme-linked immunosorbent assay. Each the antibodies had antigen subsite binding specificities in aqueous medium for small phosphate-containing molecules inositol. The anti-PIP inhibited infection two HIV-1 neutralization assays employing...