Publications

Cutting Edge: Transcriptional Profiling Reveals Multifunctional and Cytotoxic Antiviral Responses of Zika Virus-Specific CD8+ T Cells

Zika virus (ZIKV) constitutes an increasing public health
problem. Previous studies have shown that CD8+ T cells
play an important role in ZIKV-specific protective immunity.
We have previously defined antigenic targets of
the ZIKV-specific CD8+ T cell response in humans. In
this study, we characterized the quality and phenotypes of
these responses by a combined use of flow cytometry and
transcriptomic methods, using PBMCs from donors deriving
from different geographical locations collected in
the convalescent phase of infection.

Genetic Variation between Dengue Virus Type 4 Strains Impacts Human Antibody Binding and Neutralization

There are four distinct DENV serotypes, and within DENV4, there are five distinct genotypes. The impact of genotypic diversity is not known, nor is it clear whether infection with one DENV4 genotype results in protective immunity against the other genotypes. To measure the impact of DENV4 genetic diversity, we generated an isogenic panel of viruses containing the envelope protein from the different genotypes.

Development of standard clinical endpoints for use in dengue interventional trials

Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has been effective and at present, early recognition of severe dengue and timely supportive care are used to reduce mortality. While the first dengue vaccine was recently licensed, and several other candidates are in late stage clinical trials, future decisions regarding widespread deployment of vaccines and/or therapeutics will require evidence of product safety, efficacy and effectiveness. Standard, quantifiable clinical endpoints are needed to ensure reproducibility and comparability of research findings. To address this need, we established a working group of dengue researchers and public health specialists to develop standardized endpoints and work towards consensus opinion on those endpoints.

An ‘indefensible’ decision: not vaccinating pregnant and lactating women in an Ebola outbreak

The rVSV-ZEBOV vaccine is currently the only Ebola vaccine that has successfully completed efficacy trials and is being used in response efforts. This vaccine would not likely be viewed as appropriate for use in pregnant women outside the context of an Ebola outbreak.

Enterotoxigenic E. coli virulence gene regulation in human infections

Enterotoxigenic Escherichia coli (ETEC) is a global diarrheal pathogen that utilizes adhesins and secreted enterotoxins to cause disease in mammalian hosts. Decades of research on virulence factor regulation in ETEC has revealed a variety of environmental factors that influence gene expression, including bile, pH, bicarbonate, osmolarity, and glucose. However, other hallmarks of the intestinal tract, such as low oxygen availability, have not been examined.

Early transcriptional responses after dengue vaccination mirror the response to natural infection and predict neutralizing antibody titers

We characterized human genome-wide transcripts in whole blood from 10 volunteers at 11 time-points after immunization with the dengue virus type 3 (DENV-3) component of the NIH dengue vaccine candidate TV003 and from 30 hospitalized children with acute primary DENV-3 infection. We compared day-specific gene expression patterns with subsequent neutralizing antibody (NAb) titers.

The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates

The global burden of disease caused by respiratory syncytial virus (RSV) is increasingly recognised, not only in infants, but also in older adults (aged ≥65 years). Advances in knowledge of the structural biology of the RSV surface fusion glycoprotein have revolutionised RSV vaccine development by providing a new target for preventive interventions. The RSV vaccine landscape has rapidly expanded to include 19 vaccine candidates and monoclonal antibodies (mAbs) in clinical trials, reflecting the urgency of reducing this global health problem and hence the prioritisation of RSV vaccine development.

Zika vaccines and therapeutics: landscape analysis and challenges ahead

The devastating consequences of Zika virus (ZIKV) infection, leading to congenital Zika syndrome (CZS) and neurological complications such as Guillain–Barre Syndrome (GBS), led the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016, and to call on the global research and product development (R&D) communities to prioritize the development of preventative and therapeutic solutions. The R&D communities responded rapidly, with 45 vaccine candidates being initially evaluated in non-clinical studies and most progressing to active development.