Controversy and debate on dengue vaccine series—paper 2: response to review of a licensed dengue vaccine: inappropriate subgroup analyses and selective reporting may cause harm in mass vaccination programs

Hadinegoro, Sri Rezeki; Arredondo-Garcı́a, José Luis; Capeding, María Rosario; Pallardy, Sophie; Noriega, Fernando; Bouckenooghe, Alain

doi:10.1016/j.jclinepi.2017.12.024

Cited by 6 publications

(4 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results from phase III clinical trials revealed that although individuals, especially children, presented high levels of neutralizing antibodies toward DENV2 after vaccination, they were not protected against this virus (8–10). Furthermore, recent reports showed that children who were dengue naïve at vaccination time were more susceptible to develop severe dengue after virus exposure (11–13). Such results point out that the induction of neutralizing antibodies is not the only arm of the immune response involved in protection against DENV.…”

Section: Introductionmentioning

confidence: 99%

T Cell Responses Induced by DNA Vaccines Based on the DENV2 E and NS1 Proteins in Mice: Importance in Protection and Immunodominant Epitope Identification

et al. 2019

View full text Add to dashboard Cite

The importance of the cellular immune response against DENV has been increasingly highlighted in the past few years, in particular for vaccine development. We have previously constructed two plasmids, pE1D2, and pcTPANS1, encoding the envelope (E) ectodomain (domains I, II, and III) and the non-structural 1 (NS1) protein of dengue virus serotype 2 (DENV2), respectively. In the present work, we analyzed the induction of the cellular response in mice immunized with these DNA vaccines and identified the immunogenic peptides. Vaccinated BALB/c mice became protected against a lethal challenge of DENV2. Depletion of CD4 + cells in vaccinated animals almost completely abolished protection elicited by both vaccines. In contrast, a significant number of pE1D2- and pcTPANS1-immunized mice survived virus challenge after depletion of CD8 + cells, although some animals presented morbidity. To identify immunogenic peptides recognized by T cells, we stimulated splenocytes with overlapping peptide libraries covering the E and NS1 proteins and evaluated the production of IFN-γ by ELISPOT. We detected two and three immunodominant epitopes in the E and NS1 proteins, respectively, and four additional NS1-derived peptides after virus challenge. Characterization by intracellular cytokine staining (ICS) revealed that both CD4 + and CD8 + T cells were involved in IFN-γ and TNF-α production. The IFN-γ ICS confirmed reaction of almost all E-derived peptides before challenge and identified other epitopes after infection. All NS1-derived peptides were able to elicit IFN-γ production in CD4 + cells, while only a few peptides induced expression of this cytokine in CD8 + T lymphocytes. Interestingly, we observed an increase in the frequency of either CD4 + or CD8 + T cells producing TNF-α after immunization with the pE1D2 and challenge with DENV2, while lymphocytes from pcTPANS1-vaccinated animals maintained ordinary TNF-α production after virus infection. We also assessed the recognition of E and NS1 immunogenic peptides in C57BL/6 mice due to the difference in MHC haplotype expression. Two NS1-derived epitopes featured prominently in the IFN-γ response with cells from both animal strains. Overall, our results emphasize the importance of the T cell response involved in protection against dengue induced by E and NS1 based DNA vaccines.

show abstract

Section: Introductionmentioning

confidence: 99%

T Cell Responses Induced by DNA Vaccines Based on the DENV2 E and NS1 Proteins in Mice: Importance in Protection and Immunodominant Epitope Identification

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Global incidences of DENV and its associated economic burden have increased dramatically in recent years [5,6], with over 50% of the world's population now at risk of infection [7] and 390 million documented infections per year [6] for an estimated $40 billion in economic losses annually [8,9]. Moreover, there are currently no specific treatments nor preventive prophylactic measures [10] because the single commercially available vaccine [11] is only partially effective [12], and due to increased risk of severe dengue illness and hospitalization among certain groups, its use is prevented in many contexts [13][14][15]. Therefore, control of the disease-spreading mosquitoes is currently the best option for preventing DENV transmission [13].…”

Section: Introductionmentioning

confidence: 99%

Broad dengue neutralization in mosquitoes expressing an engineered antibody

Buchman

Gamez

et al. 2020

PLoS Pathog

View full text Add to dashboard Cite

With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Importantly, this is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression. These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses. Author summaryWith limited success of traditional vector control methods to curb dengue infections and more than half of the world's population still at risk, there is a need for novel strategies to reduce its impact on public health. Recent advances in genetic technologies has allowed for precise modifications of mosquito genome to make them resistant to infections, thus breaking the transmission cycle. Here we generated engineered Ae. aegypti mosquitoes PLOS Pathogens | https://doi.efficiently expressing a DENV-targeting single-chain variable fragment (scFv) derived from a previously characterized broadly neutralizing human antibody, which blocked infection and transmission in these mosquitoes. To our knowledge, this is the first example of an engineered transgene capable of rendering Ae. aegypti mosquitoes 100% refractory to all four serotypes of DENV. The engineered mosquitoes, in future, could easily be paired with a gene drive, capable of spreading the transgene throughout wild diseasetransmitting mosquito populations and preventing further DENV transmission. Since a number of diverse and well-characterized antibodies exist against other arboviruses (eg chikungunya and Zika, this work also provides a proof-of-concept principle for developing similar genetic strategies for reducing the impact of these arboviruses.

show abstract

“…In this regard, DENV has been infecting about 390 million people worldwide annually with an increasing incidence rate over the last two decades, particularly the death‐to‐case ratio [3,4] . Although there is a tetravalent vaccine for dengue fever (CYD‐TDC: Dengvaxia®), there are concerns about its safety [5,6] . Furthermore, regarding ZIKV, which is associated with neurological disorders in newborns and pediatric microcephaly, neither vaccine nor drug has been approved for it Therefore, researchers have been working on the development of molecules with potential applications against viral proteases to control this virus and other arboviruses [7,8] …”

Section: Introductionmentioning

confidence: 99%

“…[3,4] Although there is a tetravalent vaccine for dengue fever (CYD-TDC: Dengvaxia®), there are concerns about its safety. [5,6] Furthermore, regarding ZIKV, which is associated with neurological disorders in newborns and pediatric microcephaly, neither vaccine nor drug has been approved for it Therefore, researchers have been working on the development of molecules with potential applications against viral proteases to control this virus and other arboviruses. [7,8] It is worth highlighting that certain underlying factors contribute to the availability and proliferation of the Aedes aegypti, such as favorable climatic conditions in tropical and subtropical countries and the drought tolerance of the vector's eggs.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Esters Containing Cinnamoyl Motif with Potential Larvicide Action: A Computational, Ecotoxicity and in Vitro Cytotoxicity Assessments

Lima

Correia

Carvalho

et al. 2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

An increasing morbidity and mortality rate has been related to arboviruses transmitted by Aedes aegypti. Compounds with cinnamoyl moiety represent an alternative against mosquitos, considering their larvicidal activity. This study aimed to assess the larvicidal activity of cinnamic ester derivates against Aedes aegypti larvae, along with evaluating their toxicity effect to assess its safety as a larvicide. Ethyl cinnamate demonstrated larvicidal activity (LC 50 = 48.59 μg/mL). Morphological changes in larvae were detected, as a degenerative response in the thorax. Through molecular docking, the molecular binding mode between 3b, 3c, and acetylcholinesterase showed strong hydrogen bond interactions. Preliminary in vitro cell viability revealed the non-cytotoxicity of 3c. Ecotoxicity results indicated a sensitivity of Artemia salina to cinnamic esters. The phytotoxicity bioassays show potential for cinnamic compounds to enhance germination and root development. These findings suggest that compound 3c is more suitable as a larvicide since it demonstrated low toxicity.

show abstract

Controversy and debate on dengue vaccine series—paper 2: response to review of a licensed dengue vaccine: inappropriate subgroup analyses and selective reporting may cause harm in mass vaccination programs

Cited by 6 publications

References 8 publications

T Cell Responses Induced by DNA Vaccines Based on the DENV2 E and NS1 Proteins in Mice: Importance in Protection and Immunodominant Epitope Identification

T Cell Responses Induced by DNA Vaccines Based on the DENV2 E and NS1 Proteins in Mice: Importance in Protection and Immunodominant Epitope Identification

Broad dengue neutralization in mosquitoes expressing an engineered antibody

Synthesis of Esters Containing Cinnamoyl Motif with Potential Larvicide Action: A Computational, Ecotoxicity and in Vitro Cytotoxicity Assessments

Contact Info

Product

Resources

About