Safety and immunogenicity of one versus two doses of Takeda's tetravalent dengue vaccine in children in Asia and Latin America: interim results from a phase 2, randomised, placebo-controlled study

Sáez-Llorens, Xavier; Tricou, Vianney; Yu, Delia; Rivera, Luis; Tuboi, Suely; Garbes, Pedro; Borkowski, Astrid; Wallace, Derek

doi:10.1016/s1473-3099(17)30166-4

Cited by 75 publications

(42 citation statements)

References 27 publications

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“…Meanwhile, several other vaccine candidates have either progressed to clinical trials or are in the late stages of preclinical development. Thus, one of the most advanced alternatives to Dengvaxia is the DENVax vaccine developed by Takeda Vaccines Inc (Brewoo et al, 2012;Osorio et al, 2011), currently undergoing phase 2 trials in Asia and Latin America (Saez-Llorens et al, 2017). Similarly, the LAV Delta 30 (NIAD/Butantan) dengue vaccine has completed phase 1 clinical trials (Durbin et al, 2011) and is about to enter phase II trials.…”

Section: Introductionmentioning

confidence: 99%

Plant‐expressed Fc‐fusion protein tetravalent dengue vaccine with inherent adjuvant properties

Kim

Copland

Nayak

et al. 2018

Plant Biotechnology Journal

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SummaryDengue is a major global disease requiring improved treatment and prevention strategies. The recently licensed Sanofi Pasteur Dengvaxia vaccine does not protect children under the age of nine, and additional vaccine strategies are thus needed to halt this expanding global epidemic. Here, we employed a molecular engineering approach and plant expression to produce a humanized and highly immunogenic poly‐immunoglobulin G scaffold (PIGS) fused to the consensus dengue envelope protein III domain (cEDIII). The immunogenicity of this IgG Fc receptor‐targeted vaccine candidate was demonstrated in transgenic mice expressing human FcγRI/CD64, by induction of neutralizing antibodies and evidence of cell‐mediated immunity. Furthermore, these molecules were able to prime immune cells from human adenoid/tonsillar tissue ex vivo as evidenced by antigen‐specific CD4+ and CD8+ T‐cell proliferation, IFN‐γ and antibody production. The purified polymeric fraction of dengue PIGS (D‐PIGS) induced stronger immune activation than the monomeric form, suggesting a more efficient interaction with the low‐affinity Fcγ receptors on antigen‐presenting cells. These results show that the plant‐expressed D‐PIGS have the potential for translation towards a safe and easily scalable single antigen‐based tetravalent dengue vaccine.

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Section: Introductionmentioning

confidence: 99%

Plant‐expressed Fc‐fusion protein tetravalent dengue vaccine with inherent adjuvant properties

Kim

Copland

Nayak

et al. 2018

Plant Biotechnology Journal

View full text Add to dashboard Cite

show abstract

“…Although these results are presented in the context of the CYD-TDV dengue vaccine, phase II interim analysis of the Takeda TDV vaccine has also shown lower geometric mean titres (GMT) of neutralising dengue antibodies to DENV-1 to -4 in those seronegative at baseline compared to seropositive at baseline [36]. Therefore, it is possible that similar recommendations for targeting vaccination may be made for future dengue vaccines.…”

Section: Discussionmentioning

confidence: 96%

Targeting Vaccinations for the Licensed Dengue Vaccine: Considerations for Serosurvey Design

Imai

Ferguson

2017

Preprint

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Objective: WHO recommends countries consider dengue vaccination in geographic settings only where epidemiological data indicate a high burden of disease. In defining target populations, WHO recommend that prior infection with any dengue serotype should be >70% seroprevalence. Here we address considerations for serosurvey design in the context of the newly licensed CYD-TDV vaccine.Methods: To explore how the design of seroprevalence surveys (age range, survey size) would affect estimates of the force of infection, for every combination of age range, total survey size, transmission setting, and test sensitivity/specificity, 100 age-specific seroprevalence surveys were simulated using a beta-binomial distribution and a simple catalytic model. The transmission intensity was then re-estimated using a MetropolisHastings Markov Chain Monte-Carlo algorithm.Findings: Sampling from a wide age range led to more accurate estimates than having a larger sample size. This finding was consistent across all transmission settings. The optimal age range to sample from differed by transmission intensity, with younger and older ages being important in high and low transmission settings respectively. The optimum test sensitivity and specificity given an imperfect test also differed by transmission setting with high sensitivity being important in high transmission settings and high specificity important in low transmission settings.Conclusions: When assessing the suitability for vaccination by seroprevalence surveys, countries should ensure that an appropriate age range is sampled, taking into account epidemiological evidence about the local burden of dengue.

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“…Currently, some live attenuated dengue vaccines are being assessed in clinical trials. [48][49][50] DENV-EIII is the protein subdomain responsible for DENV binding to target cells; 21 therefore, DENV-EIII is a feasible vaccine candidate to elicit protective antibodies. 51 A DENV-EIIIspecific epitope-recognizing antibody that ameliorated the clinical symptoms of infection for all 4 serotypes of DENV was demonstrated in a humanized mouse model.…”

Section: Discussionmentioning

confidence: 99%

Suppressive effect of dengue virus envelope protein domain III on megakaryopoiesis

et al. 2017

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Dengue virus (DENV) infection can cause severe, life-threatening events, and no specific treatments of DENV infection are currently approved. Although thrombocytopenia is frequently observed in dengue patients, its pathogenesis is still not fully understood. Previous studies have suggested that DENV-induced thrombocytopenia occurs through viral-replication-mediated megakaryopoiesis inhibition in the bone marrow; however, the exact mechanism for megakaryopoiesis suppression remains elusive. In this study, a reductionist approach was applied, in which C57B/6J mice were inoculated with recombinant DENV-envelope protein domain III (DENV-EIII) instead of the full viral particle. Our results demonstrated that DENV-EIII-suppressed megakaryopoiesis is similar to those observed with DENV infection. Furthermore, in agreement with our in vivo analyses, DENV-EIII sufficiently suppressed the megakaryopoiesis of progenitor cells from murine bone marrow and human cord blood in vitro. Additional analyses suggested that autophagy impairment and apoptosis are involved in DENV-EIII-mediated suppression of megakaryopoiesis. These data suggest that, even without viral replication, the binding of DENV-EIII to the cell surface is sufficient to suppress megakaryopoiesis.

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Safety and immunogenicity of one versus two doses of Takeda's tetravalent dengue vaccine in children in Asia and Latin America: interim results from a phase 2, randomised, placebo-controlled study

Cited by 75 publications

References 27 publications

Plant‐expressed Fc‐fusion protein tetravalent dengue vaccine with inherent adjuvant properties

Plant‐expressed Fc‐fusion protein tetravalent dengue vaccine with inherent adjuvant properties

Targeting Vaccinations for the Licensed Dengue Vaccine: Considerations for Serosurvey Design

Suppressive effect of dengue virus envelope protein domain III on megakaryopoiesis

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