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Research

Chris Plowe
Dr. Christopher Plowe administering
malaria vaccinations.

Vaccinology is a scientific and medical discipline that encompasses and incorporates inputs from bacteriology, virology, parasitology, immunology, molecular biology, structural biology, epidemiology, public health, clinical trials, translational medicine, pediatrics, internal medicine, biostatistics, anthropology, ethics, fermentation engineering and, as necessary, other areas of expertise. 

The CVD conducts research that ranges from basic laboratory investigations of pathogenesis, mechanistic aspects of immunity and construction of vaccine development through pre-clinical animal model studies, performance of early small-scale (Phase 1 and 2) clinical trials, large-scale pivotal Phase 3 efficacy trials and post-licensure trials. 

While the main research thrust of basic research at CVD has historically focused on bacterial enteric pathogens, rotavirus and malaria, it has also worked more broadly in the areas of bacterial diseases, parasitic diseases, viral diseases, novel delivery systems, public health and vaccine policy.  As a result of many of these endeavors, the CVD generates intellectual property that is available for licensing by commercial entities.

Clinical, Laboratory, Field Sites, Consulting Activities

Inpatient clinical studies are generally performed on the Research Isolation Ward operated by at SNBL, which is located in the University of Maryland, Baltimore Biopark, across the avenue from the CVD Headquarters. Outpatient clinical vaccine studies are conducted at the CVD’s outpatient facility in Baltimore, as well as, on occasion, at the University of Maryland, College Park campus.  Off-shore clinical and field research is mainly performed at the main CVD field units including CVD - Chile (Santiago, Chile), CVD-Mali and CVD-Malawi.  Other focused field research activities that endure for more finite periods are carried out in various other sites around the world as dictated by the specific project.  Some examples of where studies have been undertaken include Pakistan, India, Thailand, Kenya, Mozambique, Bangladesh, Ethiopia, Peru, Indonesia, Costa Rica, Honduras, Panama, Venezuela.

CVD trainees (post-doctoral fellows and students) and faculty participate in these off-shore projects thereby providing opportunities for them to participate in Global Health training and work activities, as well as in technology transfer.

Faculty and staff consult with international agencies and foundations such as the World Health Organization, Pan American Health Organization, Agency for International Development, World Bank, the Rockefeller Foundation, the GAVI Alliance and the Bill & Melinda Gates Foundation, as well as with individual governments and pharmaceutical manufacturers.

Pipeline of CVD Vaccines in Various Stages of Development

CVD 103-HgR -- Single-dose live oral cholera vaccine on an accelerated track for licensure by the US FDA (PaxVax as manufacturer).

CVD 908-htrA -- Single-dose live oral typhoid vaccine that proved to be well-tolerated and immunogenic in Phase 2 trials.  CVD 0908-htrA has also been used as a live vector vaccine.

CVD 909 --  Live typhoid vaccine expressing Vi antigen constitutively (Phase 2)

CVD 1902 Attenuated S. Paratyphi A strain serving as a live oral vaccine (Phase 1 completed).

CVD 909 plus CVD 1902.  CVD 909 and CVD 1902 are being proposed as a bivalent oral enteric fever combination vaccine.

Quadrivalent and pentavalent Shigella vaccines. The quadrivalent oral vaccine will consist of attenuated S. flexneri 2a, S. flexneri 3a, S. flexneri 6 and S. sonnei. Prototype attenuated S. flexneri 2a strain CVD 1208S has been evaluated in Phase 2 as a live oral vaccine.  The pentavalent version will include, in addition, an attenuated S. dysenteriae 1 vaccine strain. Although wild type S. dysenteriae 1 is capable of causing large-scale propagated outbreaks and pandemics of clinically severe disease, at the current time it has virtually disappeared from the global scene. So at present, a quadrivalent combination vaccine will suffice to achieve broad protection.

Combination live vector Shigella-ETEC oral vaccine (Phase 1).  The five attenuated Shigella strains in the pentavalent vaccine are each engineered to express two colonization factor fimbriae or heat-labile toxin B subunit antigens of enterotoxigenic Escherichia coli (ETEC).  Collectively this creates a multivalent combination Shigella-ETEC oral vaccine capable of eliciting broad spectrum protection against both of those enteric pathogens.

NTS bivalent conjugate – CVD, in partnership with Bharat Biotech International of Hyderabad, India and the Wellcome Trust are developing a bivalent non-typhoidal Salmonella conjugate vaccine based on covalently linking the core and O-polysaccharides of S. Typhimurium and S. Enteritidis, respectively, to the Phase 1 flagellin subunits of those serovars. Highly engineered, flagellin hyper-expressing “reagent strains” provide a safe (from the occupational health perspective) and economical source of antigens to manufacture the conjugates.

NTS live oral vaccine – Attenuated strains of S. Typhimurium and S. Enteritidis have been prepared to serve as a bivalent live oral vaccine approach to prevent invasive NTS disease and perhaps also NTs gastroentreritis.

S. Typhi live vector-based live oral Clostridium difficile vaccine.  Expression of putative protective antigens of C. difficile in an attenuated S. Typhi live vector.

Anthrax, plague & tularemia vaccines.  Various biodefense vaccines

 pMSINH --  New measles DNA vaccine for very young infants in developing countries.  This is based on a Sindbis replicon that encodes the H antigen protein of measles virus.