A5048058406- Malaria Research and Control
- Mosquito-borne diseases and control
- vaccines and immunoinformatics approaches
- HIV Research and Treatment
- Vector-borne infectious diseases
- Immunotherapy and Immune Responses
- Hepatitis B Virus Studies
- Complement system in diseases
- Pneumonia and Respiratory Infections
- Travel-related health issues
- Computational Drug Discovery Methods
- Diverse Cultural and Historical Studies
- French Urban and Social Studies
- Immune Cell Function and Interaction
- Invertebrate Immune Response Mechanisms
- Trypanosoma species research and implications
- T-cell and B-cell Immunology
- Herpesvirus Infections and Treatments
- Immunodeficiency and Autoimmune Disorders
- T-cell and Retrovirus Studies
- Parasites and Host Interactions
- Bacterial Infections and Vaccines
- Viral Infections and Vectors
- Monoclonal and Polyclonal Antibodies Research
- HIV/AIDS oral health manifestations
National Institutes of Health
1998-2025
National Institute of Allergy and Infectious Diseases
2023-2025
Naval Medical Research Command
2012-2022
United States Department of the Navy
2014
Fundación Valle del Lili
2011
Universidad Nacional de Colombia
2009
Universidad del Valle
2009
Protein Potential (United States)
2008
Uniformed Services University of the Health Sciences
2007
Boston Children's Hospital
1996-2001
Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) mosquito bites. We report that the PfSPZ Vaccine--composed attenuated, aseptic, purified, cryopreserved PfSPZ--was safe and well tolerated when administered four to six times intravenously (IV) 40 adults. Zero subjects receiving five doses three nine 1.35 × 10(5) Vaccine nonvaccinated controls developed after controlled infection (P =...
Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown induce such protection humans. Such thought be mediated CD8(+) T cells liver secrete interferon-γ (IFN-γ). We report purified irradiated PfSPZ 80 volunteers needle inoculation skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated intravenous immunization...
BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy heterologous (different from vaccine), fewer doses, and at 24 weeks. METHODS: trial assessed tolerability, safety, immunogenicity, direct venous inoculation (DVI) or...
We assessed immunogenicity of a malaria DNA vaccine administered by needle i.m. or needleless jet injection [i.m. i.m./intradermally (i.d.)] in 14 volunteers. Antigen-specific IFN-γ responses were detected enzyme-linked immunospot (ELISPOT) assays all subjects to multiple 9- 23-aa peptides containing class I and/or II restricted epitopes, and dependent on both CD8 + CD4 T cells. Overall, frequency response was significantly greater after injection. -dependent cytotoxic lymphocytes (CTL) 8/14...
Background Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost vaccine Phase 1 clinical trial with controlled human infection. Methodology/Principal Findings The regimen was three monthly doses of two plasmids (DNA) followed four months later by single non-replicating serotype 5 adenovirus vectors (Ad). constructs...
ABSTRACT Levels of the serum opsonin mannan-binding lectin (MBL) were directly correlated with probability developing visceral leishmaniasis. Monocytes infected MBL-opsonized Leishmania chagasi promastigotes secreted higher levels tumor necrosis factor alpha and interleukin-6 than cells nonopsonized parasites. Our findings indicate that MBL can modulate clinical outcome infection L. function macrophages.
Challenge of volunteers by the bites membrane-fed anopheline mosquitoes infected with Plasmodium falciparum was reported in 1986. In 1997, an analysis experience 118 indicated that mosquito inoculation P. could be a safe, well-tolerated, reproducible, and efficient method challenge.We reviewed records 47 challenged at our institution NF54 isolate between 1998 2002. We also data from 17 published studies experimental challenge conducted since 1996.At institution, time to onset first symptoms...
A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vectors induce these responses in humans, a Phase 1/2a clinical trial was conducted evaluate the efficacy of an serotype 5-vectored against sporozoite challenge.NMRC-MV-Ad-PfC is vector encoding Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It one component two-component NMRC-M3V-Ad-PfCA consisting adenovector CSP apical membrane antigen-1 (AMA1) that evaluated for...
Background Exposing healthy human volunteers to Plasmodium falciparum-infected mosquitoes is an accepted tool evaluate preliminary efficacy of malaria vaccines. To accommodate the demand vaccine pipeline, controlled infections are carried out in increasing number centers worldwide. We assessed their safety and reproducibility. Methods reviewed parasitological data from 128 malaria-naïve subjects participating infection trials conducted at University Oxford, UK, Radboud Nijmegen Medical...
Vaccine-induced protection against diseases like malaria, AIDS, and cancer may require induction of Ag-specific CD8(+) CD4(+) T cell Ab responses in the same individual. In humans, a recombinant Plasmodium falciparum circumsporozoite protein (PfCSP) candidate vaccine, RTS,S/adjuvant system number 2A (AS02A), induces cells Abs, but no measurable by CTL or short-term (ex vivo) IFN-gamma ELISPOT assays, partial protection. P. DNA vaccines elicit these We report that sequential immunization with...
Background Models of immunity to malaria indicate the importance CD8+ T cell responses for targeting intrahepatic stages and antibodies sporozoite blood stages. We designed a multistage adenovirus 5 (Ad5)-vectored Plasmodium falciparum vaccine, aiming induce both types in humans, that was tested safety immunogenicity Phase 1 dose escalation trial Ad5-seronegative volunteers. Methodology/Principal Findings The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite...
A safe and reproducible Plasmodium vivax infectious challenge method is required to evaluate the efficacy of malaria vaccine candidates. Seventeen healthy Duffy (+) five (−) subjects were randomly allocated into three (A–C) groups exposed bites 2–4 Anopheles albimanus mosquitoes infected with derived from donors. included as controls for each group. Clinical manifestations parasitemia monitored beginning 7 days post-challenge. All volunteers developed patent infection within 16 after...
Background Fifteen volunteers were immunized with three doses of plasmid DNA encoding P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1) boosted human adenovirus-5 (Ad) expressing the same antigens (DNA/Ad). Four (27%) demonstrated sterile immunity to controlled malaria infection and, overall, protection was statistically significantly associated ELISpot CD8+ T cell IFN-γ activities AMA1 but not CSP. priming required for protection, as 18 additional subjects Ad...
Background Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites (RAS) results in high-level protection against infection. Only two have been similarly immunized P. vivax (Pv) RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety protective efficacy of PvRAS immunization. Methodology/Principal Findings randomized, single-blinded conducted. Duffy positive (Fy+; Pv susceptible) individuals...
Introduction of a new vaccine requires choosing delivery system that provides safe administration and the desired level immunogenicity. The safety, tolerability, immunogenicity three monthly 2.5-mg doses PfCSP DNA were evaluated in healthy volunteers as administered intramuscularly (IM) by needle, IM jet injection (Biojector®) or IM/intradermally (ID) injection. Vaccine was well-tolerated. Adverse events primarily mild limited to site (98%). Jet injections (either ID) associated with...
ABSTRACT A mixture of DNA plasmids expressing five Plasmodium falciparum pre-erythrocyte-stage antigens was administered with or without a plasmid encoding human granulocyte-macrophage colony-stimulating factor (hGM-CSF) as an immune enhancer. After immunization, antigen-specific gamma interferon (IFN-γ) responses were detected by ELISPOT in 15/31 volunteers to multiple class I- and/or II-restricted T-cell epitopes derived from all antigens. Responses (≤7) simultaneously some volunteers. By...