Analysis of cell-mediated immune responses in support of dengue vaccine development efforts

Rothman, Alan L.; Currier, Jeffrey R.; Friberg, Heather; Mathew, Anuja

doi:10.1016/j.vaccine.2015.09.104

Cited by 10 publications

(13 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IFN‐γ could play an important role in protection against dengue infection as suggested previously (Gil et al ., ; Weiskopf et al ., ). Indeed, the role of cellular immunity in protection against dengue infection has been recently re‐appraised (Rothman et al ., ) as it seems increasingly plausible that more than just neutralizing antibodies are required to control viremia.…”

Section: Discussionmentioning

confidence: 99%

Molecular engineering and plant expression of an immunoglobulin heavy chain scaffold for delivery of a dengue vaccine candidate

Kim

Dolleweerd

Copland

et al. 2017

Plant Biotechnology Journal

View full text Add to dashboard Cite

SummaryIn order to enhance vaccine uptake by the immune cells in vivo, molecular engineering approach was employed to construct a polymeric immunoglobulin G scaffold (PIGS) that incorporates multiple copies of an antigen and targets the Fc gamma receptors on antigen‐presenting cells. These self‐adjuvanting immunogens were tested in the context of dengue infection, for which there is currently no globally licensed vaccine yet. Thus, the consensus domain III sequence (cEDIII) of dengue glycoprotein E was incorporated into PIGS and expressed in both tobacco plants and Chinese Ovary Hamster cells. Purified mouse and human cEDIII‐PIGS were fractionated by HPLC into low and high molecular weight forms, corresponding to monomers, dimers and polymers. cEDIII‐PIGS were shown to retain important Fc receptor functions associated with immunoglobulins, including binding to C1q component of the complement and the low affinity Fcγ receptor II, as well as to macrophage cells in vitro. These molecules were shown to be immunogenic in mice, with or without an adjuvant, inducing a high level IgG antibody response which showed a neutralizing potential against the dengue virus serotype 2. The cEDIII‐PIGS also induced a significant cellular immune response, IFN‐γ production and polyfunctional T cells in both the CD4+ and CD8+ compartments. This proof‐of‐principle study shows that the potent antibody Fc‐mediated cellular functions can be harnessed to improve vaccine design, underscoring the potential of this technology to induce and modulate a broad‐ranging immune response.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular engineering and plant expression of an immunoglobulin heavy chain scaffold for delivery of a dengue vaccine candidate

Kim

Dolleweerd

Copland

et al. 2017

Plant Biotechnology Journal

View full text Add to dashboard Cite

show abstract

“…We used overlapping peptides encompassing the entire DENV genome and were able to detect significant IFN-γ responses to many peptide pools. Of note, IFN-γ responses were detected more frequently against non-structural pools similar to what has been detected in humans [19]. Our efforts to expand T cells in splenocytes with either specific DENV peptides or infectious DENV from immune BLT NSG mice were not successful (data not shown) as we have routinely performed using dengue immune PBMC in humans.…”

Section: T Cell Responses To Natural Dengue Infection In Humans and Hmentioning

confidence: 94%

“…In humans, both CD4+ and CD8+ T cells are generated in response to natural infection with DENV [19]. A number of CD4+ and CD8+ T cell epitopes have been defined and are directed against both structural and non-structural proteins on DENV although non-structural proteins are a dominant target for CTL recognition [20].…”

Section: T Cell Responses To Natural Dengue Infection In Humans and Hmentioning

confidence: 99%

Humanized mouse models to study human cell-mediated and humoral responses to dengue virus

Mathew

2017

Current Opinion in Virology

Self Cite

View full text Add to dashboard Cite

Several candidate dengue virus vaccines are in clinical trials and show promise as an effective measure to control dengue. However, it is becoming clear that additional vaccine candidates may be needed as there is concern about the durability of the immune response to all four serotypes of vaccine components and efficacy varies dependent on the immune status of the individual. The lack of an appropriate animal model to mimic human dengue has deterred the development of vaccines and anti-viral therapies to dengue virus. The focus of this review is to discuss advances in the development of humanized animal models and to highlight how they could be used for antiviral and dengue vaccine testing if limitations with cell-mediated immunity and seroconversion to IgG are overcome.

show abstract

“…Moreover, two successful flavivirus vaccines (JEV and TBEV vaccines) are based on inactivated virions in the absence of NS proteins (Ishikawa et al, 2014). Although it remains to be investigated whether NS proteins are required to be a component of dengue vaccine, evaluation of dengue vaccine in clinical trials should include the assessment of T-cell responses (Rothman et al, 2015). …”

Section: T-cell Responses After Natural Denv Infectionmentioning

confidence: 99%

Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development

2017

View full text Add to dashboard Cite

The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur), a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5–60.8%) in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs) against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

show abstract

Analysis of cell-mediated immune responses in support of dengue vaccine development efforts

Cited by 10 publications

References 92 publications

Molecular engineering and plant expression of an immunoglobulin heavy chain scaffold for delivery of a dengue vaccine candidate

Molecular engineering and plant expression of an immunoglobulin heavy chain scaffold for delivery of a dengue vaccine candidate

Humanized mouse models to study human cell-mediated and humoral responses to dengue virus

Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development

Contact Info

Product

Resources

About