A new vaccination strategy for dengue virus (DENV) was evaluated in rhesus macaques by priming with tetravalent purified inactivated virus (TPIV) which is a WRAIR vaccine or tetravalent plasmid DNA vaccines expressing the structural prME gene region (TDNA) then boosting 2 months later with a tetravalent live attenuated virus (TLAV) vaccine. Both vaccine combinations elicited virus neutralizing (N) antibodies. The TPIV/TLAV combination afforded complete protection against DENV 3 challenge at month 8. In a second experiment, priming with TPIV elicited N antibodies against all four serotypes (GMT 1:28 to 1:43). Boosting with TLAV led to an increase in the GMT for each serotype (1:500 to 1:1200 for DENVs 1, 3, and 4, and greater than 1:6000 for DENV 2), which declined by month 8 (GMT 1:62 for DENV 3, 1:154 for DENV 1, 1:174 for DENV 4, and 1:767 for DENV 2). After challenge with each one of the four DENV serotypes, vaccinated animals exhibited no viremia but showed anamnestic antibody responses to the challenge viruses. Currently, WRAIR is involved in conducting early stage clinical trials on the Tetravalent Purified-Inactivated Virus (TPIV) Vaccine for Dengue.
A A suite of freely-available software tools for electronic disease surveillance in resource-limited settings from Johns Hopkins applied physics laboratory and the Armed Forces Health Surveillance Center (AFHSB). Public health surveillance is undergoing a revolution driven by advances in the field of information technology. Many countries have experienced vast improvements in the collection, ingestion, analysis, visualization, and dissemination of public health data. Resource-limited countries have lagged behind due to challenges in information technology infrastructure, public health resources, and the costs of proprietary software. The Suite for Automated Global Electronic bioSurveillance (SAGES) is a collection of modular, flexible, freely-available software tools for electronic disease surveillance in resource-limited settings. One or more SAGES tools may be used in concert with existing surveillance applications or the SAGES tools may be used en masse for an end-to-end biosurveillance capability. This flexibility allows for the development of an inexpensive, customized, and sustainable disease surveillance system. The ability to rapidly assess anomalous disease activity may lead to more efficient use of limited resources and better compliance with World Health Organization International Health Regulations. reference PLoS ONE 6(5): e19750.doi:10.1371/journal.pone.0019750
Mission: To be a prepared and fully functional cGMP manufacturing facility at all times in order to aid Army researchers in the development of vaccines for the war fighter. To achieve the mission of being ready and fully trained, the WRAIR PBF must continually develop and maintain projects and working relationships with other government entities (NIH, USAID, etc.) through Interagency Agreements and with universities and commercial companies and other private organizations through Cooperative Research and Development Agreements (CRADAs). Capabilities: Serving various clients and principal investigators, the WRAIR PBF can provide Phase1 and Phase 2 cGMP bacterial and viral vaccine constructs/production as follows: 1) Live, attenuated, killed or purified protein based vaccines; 2) Master and production seed/cell banking; 3) Fermentation (to 300 liters); 4) Protein purification; 5) Viral purification; 6) Aseptic filling of final vaccine material (validated to 2000 vials); 7) Lyophilization of final or bulk material; 8) Various types of vaccine product testing; 9) Specialized viral testing; 10) Stability program administration and testing for manufactured products. Major Accomplishments: 1)19 years of continual GMP manufacturing; 2) Worked with over 50 different clients/organizations; 3) Four products initiated at the PBF reaching licensure; 4) Pristine record of aseptic filling validation; 5)Type V Facility Master File filed and maintained at the FDA; 6) Excellent record of flexible and supportive service and interactions with clients; 7) Continual implementation of Validation Master Plan Fully developed GMP documentation system.
The Chemical Information System (CIS) is a research and management tool developed by the Department of Chemical Information (formerly the Chemical Handling and Data Analysis Branch). CIS use and function has evolved from a relatively simple inventory system to a powerful, integrated, Cheminformatics research and management tool. In recognition of the CIS's complexity and uniqueness, the United States Patent Office has granted Patent Number 6,654,736.
A method for the quantitation of small molecules from dried blood spots to accurately measure single nanogram/mL amounts of material from 15 microL of dried blood or plasma. Dried blood spots can be stored and shipped easily, facilitating measurements in conjunction with drug compliance studies or clinical trials conducted in austere environments where the collection, separation, and shipment of frozen plasma is not logistically feasible.
The technique called - codon harmonization - that combines bioinformatics, protein chemistry and genetic engineering to produce novel re-coded gene sequences for expressing recombinant antigens. Codon harmonization addresses several problems inherent to expressing proteins in heterologous hosts such as protein folding and insolubility. Such problems may be due to incorrect modulation of localized translations rates in the heterologous expression host. Codon harmonization engineers recombinant genes with synonymous codons so that codon usage frequencies match those found in the native host for expression in the heterologous host. Particular attention is focused on regions coded by low abundance t-RNA isoacceptor molecules which are predictive of interdomain, nonstructural regions within the protein. WRAIR has applied this technique to several malaria parasite genes including Pf MSP1-42 3D7, Pf MSP1-42 FVO, Pf MSP1-42 CAMP-FUP, Pf LSA1 and PfCelTOS, and has several patent applications related to this technique.
The Clinical Trials Center (CTC) was established as a clinical research unit in 1992 to support military, Federal, and industrial partners in their mission to develop new vaccines, drugs, and diagnostic systems that will benefit not only the military, but all people. An average of 13-15 clinical studies are conducted each year through the CTC. To implement these studies, the CTC recruits over 350 human volunteers per year. Services: Design and implementation of Phase I, II, and III clinical protocols; Consultative support in all aspects of study design; Recruitment and management of study volunteers; Design and maintenance of clinical records, case report forms and databases; On-site storage and monitoring of study vaccines and medication; Outpatient facilities with full clinical support staff for study visits; Quality Assurance WRAIR also provides regulatory services: Development of regulatory strategies for new product submissions, preparation of regulatory documents and their submission to the FDA.
WRAIR has developed and patented a novel hybrid molecule containing both Type 1 VK210 and Type 2 VK247 P. vivax repeats. This molecule VMP001 induces a potent immune response to both Type 1 and Type 2 sporozoites in animal models. In addition to the repeat region, the recombinant molecule contains the N- and C-terminal regions of CS protein including several T and B cell epitopes.
CelTOS (also known as Ag2) is a highly conserved antigen that is expressed in malaria preerythrocytic sporozoites and sexual stage ookinetes; in addition, it is involved in sporozoite invasion of hepatocytes. WRAIR has developed and patented a His-tagged recombinant protein of full length CelTOS from both P. berghei and P. falciparum.
WRAIR has an established Veterinary Medicine Facility that offers collaborations for preclinical studies with non-human primates and other animals. WRAIR has a Nonhuman Primate Specific Pathogen Free Colony of Indian Origin Rhesus Macaques available for collaborative studies in tropical disease research, testing vaccines and therapeutics for malaria, leishmaniasis and dengue fever.