Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial

Kallás, Esper G.; Precioso, Alexander Roberto; Palácios, Ricardo; Thomé, Beatriz; Braga, Patrícia Emília; Vanni, Tázio; Campos, Lúcia M A; Ferrari, Lilian Pereira; Mondini, Gabriela; Salomão, Maria da Graça; Silva, Anderson Rodrigo da; Espínola, Heloísa Maximo; Santos, Joane do Prado; Santos, Cecília Luiza Simões; Timenetsky, María do Carmo Sampaio Tavares; Miraglia, João Luiz; Gallina, Neuza Maria Frazatti; Weiskopf, Daniela; Sette, Alessandro; Goulart, Raphaella; Salles, Rafael Tavares; Maestri, Alvino; Sallum, Adriana Maluf Elias; Farhat, Sylvia Costa Lima; Sakita, Neusa Keico; Ferreira, Juliana Carvalho; Silveira, Cássia G. T.; Costa, Priscilla R.; Raw, Isaı́as; Whitehead, Stephen S.; Durbin, Anna P.; Kalil, Jorge

doi:10.1016/s1473-3099(20)30023-2

Cited by 58 publications

(56 citation statements)

References 28 publications

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“…12,13 The tetravalent live attenuated dengue vaccine candidate TV003 from the National Institute of Allergy and Infectious Diseases has progressed though Phase I and II clinical studies, including in endemic areas, where it has proven to be safe and able to induce neutralizing antibodies against all four DENV serotypes. [14][15][16][17][18] TV003 is now in a Phase III clinical trial (NCT02406729) in endemic areas. TV003 completely protected flavivirus-naive adult subjects from clinical symptoms and dengue viremia, as measured by virus culture and RT-PCR, following challenge with a recombinant heterotypic DENV2, known as rDEN2D30.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of B Cell Immunity in Flavivirus-Naive Individuals by the Tetravalent Live Attenuated Dengue Vaccine TV003

Nivarthi

Graham

et al. 2020

Cell Reports Medicine

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Summary The tetravalent live attenuated dengue vaccine candidate TV003 induces neutralizing antibodies against all four dengue virus serotypes (DENV1–DENV4) and protects against experimental challenge with DENV2 in humans. Here, we track vaccine viremia and B and T cell responses to this vaccination/challenge model to understand how vaccine viremia links adaptive immunity and development of protective antibody responses. TV003 viremia triggers an acute plasmablast response that, in combination with DENV-specific CD4 + T cells, correlates with serum neutralizing antibodies. TV003 vaccinees develop DENV2-reactive memory B cells, including serotype-specific and multivalent specificities in line with the composition of serum antibodies. There is no post-challenge plasmablast response in vaccinees, although stronger and earlier post-TV003 plasmablast responses associate with sterile humoral protection from DENV2 challenge. TV003 vaccine triggers plasmablasts and memory B cells, which, with support from CD4 + T cells, functionally link early vaccine viremia and the serum antibody responses.

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Section: Introductionmentioning

confidence: 99%

Stimulation of B Cell Immunity in Flavivirus-Naive Individuals by the Tetravalent Live Attenuated Dengue Vaccine TV003

Nivarthi

Graham

et al. 2020

Cell Reports Medicine

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“…Discrimination between vaccinated and field-infected animals is possible due to the use of the prM and E proteins only in the vaccine. Finally, in our study, although the heterologous prime-boost strategy could cause a strong protective effect in animal experiments, safety evaluation is also necessary, as it is critical for every live vaccine to undergo a safety evaluation [47]. This research will also become the focus of our follow-up work, aiming at a more comprehensive evaluation of this heterologous prime-boost regimen.…”

Section: Discussionmentioning

confidence: 99%

Heterologous prime-boost: an important candidate immunization strategy against Tembusu virus

Pan

Jia

et al. 2020

Virol J

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Background: Tembusu virus (TMUV), a newly emerging pathogenic flavivirus, spreads rapidly between ducks, causing massive economic losses in the Chinese duck industry. Vaccination is the most effective method to prevent TMUV. Therefore, it is urgent to look for an effective vaccine strategy against TMUV. Heterologous prime-boost regimens priming with vaccines and boosting with recombinant adenovirus vaccines have been proven to be successful strategies for protecting against viruses in experimental animal models. Methods: In this study, heterologous and homologous prime-boost strategies using an attenuated salmonella vaccine and a recombinant adenovirus vaccine expressing prM-E or the E gene of TMUV were evaluated to protect ducks against TMUV infection for the first time, including priming and boosting with the attenuated salmonella vaccine, priming and boosting with the recombinant adenovirus vaccine, and priming with the attenuated salmonella vaccine and boosting with the recombinant adenovirus vaccine. Humoral and cellular immune responses were detected and evaluated. We then challenged the ducks with TMUV at 12 days after boosting to assay for clinical symptoms, mortality, viral loads and histopathological lesions after these different strategies. Results: Compared with the homologous prime-boost strategies, the heterologous prime-boost regimen produced higher levels of neutralizing antibodies and IgG antibodies against TMUV. Additionally, it could induce higher levels of IFN-γ than homologous prime-boost strategies in the later stage. Interestingly, the heterologous prime-boost strategy induced higher levels of IL-4 in the early stage, but the IL-4 levels gradually decreased and were even lower than those induced by the homologous prime-boost strategy in the later stage. Moreover, the heterologous prime-boost strategy could efficiently protect ducks, with low viral titres, no clinical symptoms and histopathological lesions in this experiment after challenge with TMUV, while slight clinical symptoms and histopathological lesions were observed with the homologous prime-boost strategies.

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“…The attenuating mutations of both the DENV2-PDK-53 and rDEN4Δ30vaccine strains are known, and in each vaccine strain they are located outside the structural protein coding region 29,45 . Both DENV2-PDK-53 and rDEN4Δ30 have been successfully repurposed as backbones for chimeric vaccines [45][46][47] . The Takeda TAK-003 (or DENVax) tetravalent dengue vaccine contains DENV2-PDK-53 itself, as well as three chimeric viruses which utilise DENV2-PDK-53 as their backbone 13,14,18 .…”

Section: Discussionmentioning

confidence: 99%

“…The Takeda TAK-003 (or DENVax) tetravalent dengue vaccine contains DENV2-PDK-53 itself, as well as three chimeric viruses which utilise DENV2-PDK-53 as their backbone 13,14,18 . The NIH TV003 tetravalent dengue vaccine contains DEN4Δ30 itself, as well as a chimeric DENV2/4 which utilises rDEN4Δ30as its backbone [45][46][47] . However, the DENV2-PDK-53 vaccine strain is the more established vaccine backbone, as the Takeda TAK-003 has already completed phase II & III clinical trials, while the NIH TV003 vaccine has only completed phase II clinical trials 13,14,[45][46][47] .…”

Section: Discussionmentioning

confidence: 99%

A single-dose live attenuated chimeric vaccine candidate against Zika virus

et al. 2021

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The mosquito-borne Zika virus is an emerging pathogen from the Flavivirus genus for which there are no approved antivirals or vaccines. Using the clinically validated PDK-53 dengue virus vaccine strain as a backbone, we created a chimeric dengue/Zika virus, VacDZ, as a live attenuated vaccine candidate against Zika virus. VacDZ demonstrates key markers of attenuation: small plaque phenotype, temperature sensitivity, attenuation of neurovirulence in suckling mice, and attenuation of pathogenicity in interferon deficient adult AG129 mice. VacDZ may be administered as a traditional live virus vaccine, or as a DNA-launched vaccine that produces live VacDZ in vivo after delivery. Both vaccine formulations induce a protective immune response against Zika virus in AG129 mice, which includes neutralising antibodies and a strong Th1 response. This study demonstrates that VacDZ is a safe and effective vaccine candidate against Zika virus.

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Safety and immunogenicity of the tetravalent, live-attenuated dengue vaccine Butantan-DV in adults in Brazil: a two-step, double-blind, randomised placebo-controlled phase 2 trial

Cited by 58 publications

References 28 publications

Stimulation of B Cell Immunity in Flavivirus-Naive Individuals by the Tetravalent Live Attenuated Dengue Vaccine TV003

Stimulation of B Cell Immunity in Flavivirus-Naive Individuals by the Tetravalent Live Attenuated Dengue Vaccine TV003

Heterologous prime-boost: an important candidate immunization strategy against Tembusu virus

A single-dose live attenuated chimeric vaccine candidate against Zika virus

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