A5034205739- Malaria Research and Control
- Mosquito-borne diseases and control
- Immune Cell Function and Interaction
- Invertebrate Immune Response Mechanisms
- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Complement system in diseases
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- Viral Infectious Diseases and Gene Expression in Insects
- Trypanosoma species research and implications
- Vector-borne infectious diseases
- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- Toxoplasma gondii Research Studies
- RNA and protein synthesis mechanisms
- Virology and Viral Diseases
- Insect Resistance and Genetics
- Transgenic Plants and Applications
- Computational Drug Discovery Methods
- Viral Infections and Vectors
- Viral gastroenteritis research and epidemiology
- Hepatitis B Virus Studies
Johns Hopkins University
2016-2025
General Motors (United States)
2024
Michigan United
2024
National Institute of Malaria Research
2022
University of Baltimore
2022
Fred Hutch Cancer Center
2020
Cancer Research Center
2020
Johns Hopkins Medicine
2020
New York University
1994-2003
Columbia University Irving Medical Center
1982-1999
Protective immunity against malaria can be obtained by vaccination with irradiated sporozoites. The protective antigens known as circumsporozoite (CS) proteins, are polypeptides that cover the surface membrane of parasite. CS proteins contain species-specific immunodominant epitopes formed tandem repeated sequences amino acids. Here it is shown dominant epitope Plasmodium falciparum contained in synthetic dodecapeptide Asn-Ala-Asn-Pro-Asn-Ala-Asn-Pro-Asn-Ala-Pro or (NANP)3. Monoclonal...
We have used panels of monoclonal antibodies to circumsporozoite (CS) proteins Plasmodium falciparium, P. vivax, and knowlesi determine the number topographically independent epitopes these antigens. The results competition binding assays indicated that single regions CS molecules were recognized by homologous antibodies. Competition also study specificity contained in sera humans monkeys had developed sterile immunity after immunization with irradiated, intact sporozoites. found inhibited...
Abstract Over 75% of malaria-attributable deaths occur in children under the age 5 years. However, first malaria vaccine recommended by World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategies, including monoclonal antibodies, will be important efforts to eradicate malaria. Here we characterize circulating B cell repertoires 45 vaccinees and discover antibodies development as potential therapeutics. We generated >28,000...
The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within Plasmodium falciparum circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses whole sporozoites, we identified a class of mAbs that cryptic PfCSP epitope is only exposed after cleavage subsequent pyroglutamylation (pGlu) newly formed N terminus. This pGlu-CSP not targeted by current...
An ELISPOT assay to detect and determine the number of antigen specific CD8+ T cells was standardized using cloned murine for epitope SYVPSAEQI a rodent malaria antigen. This is based on detection IFN-γ secretion by single after their stimulation with The interferon visualized as spots revealed enzyme labeled anti-IFN-γ monoclonal antibodies. Using known numbers it determined that detects 80–95% these cells. optimal culture conditions were concentration, presenting supplement growth factors...
We show here an effective and novel approach to engineer peptide-based vaccines using a chemically defined system, known as multiple peptide antigen systems (MAPs), protect inbred mouse strain from infection against rodent malaria. 10 mono- di-epitope MAP models containing different arrangements stoichiometry of functional B and/or T helper cell epitopes the circumsporozoite protein Plasmodium berghei were used immunize A/J mice. While these mice did not respond mono-epitope bearing only or...
Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas responses most antigens require further collaboration between primed, antigen-specific helper naive or memory B cells. To determine whether delivered DCs organs induce help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), the presence of maturation stimulus assayed antibodies...
Live vectors expressing foreign antigens have been used to induce immunity against several pathogens. However, for the virulent rodent malaria parasite Plasmodium yoelii, use of recombinant vaccinia virus, pseudorabies or Salmonella, circumsporozoite protein this parasite, failed protection. We generated a influenza virus an epitope from P. yoelii known be recognized by CD8+ T cells and demonstrated that vector induced class I major histocompatibility complex-restricted cytotoxic epitope....
A clone of complementary DNA encoding the circumsporozoite (CS) protein human malaria parasite Plasmodium falciparum has been isolated by screening an Escherichia coli library with a monoclonal antibody to CS protein. The sequence insert encodes four-amino acid sequence: proline-asparagine-alanine-asparagine, tandemly repeated 23 times. β-lactamase fusion specifically binds antibodies and inhibits binding these native These findings provide basis for development vaccine against malaria.
A synthetic peptide, (DPPPPNPN)2D, representing a subunit of the repeat domain Plasmodium berghei circumsporozoite protein, was conjugated to tetanus toxoid using bisdiazobenzidine. Immunization mice and rats with conjugate induced high serum titers antibodies parasite, most animals were completely protected from malaria infection when challenged sporozoites.
Immunization of BALB/c mice with radiation-attenuatedPlasmodium yoelll sporozoites induces cytotoxic T lymphocytes (CTL) specific for an epitope located within the amino acid sequence 277-288 P. circumsporozoite (CS) protein.Several CD8+ CTL clones were derived from spleen cells sporozolte-immunlzed mice, all displaying apparently Identical specificity.All Induced high levels cytolysls In vitro upon exposure to peptide-Incubated MHC-compatlble target cells.The adoptive transfer two these...
The functional role of gamma delta T cells (expressing the heterodimeric T-cell receptor for antigen) in infectious diseases remains largely unknown. We have therefore attempted to define possible these immune response against various developmental stages malaria parasites. For this purpose, we monitored and development liver blood Plasmodium yoelii, a rodent parasite, immunized nonimmunized alpha beta T-cell-deficient mice. Immunization mice with irradiated sporozoites induced an that...
Abstract The present findings establish the lack of genetic restriction humoral immune response to sporozoites Plasmodium berghei , corraborating earlier observations that mice different strains can be protected by immunization with irradiated sporozoites. Most, if not all, anti‐sporozoite antibodies are directed against repetitive B cell epitope circumsporozoite (CS) protein. However, neither a peptide containing dimer this repeat (17.1), nor polymer multiple repeats induced an antibody in...