Tetravalent dengue DIIIC protein together with alum and ODN elicits a Th1 response and neutralizing antibodies in mice

Zuest, Roland; Valdés, Iris; Skibinski, David; Lin, Yu-Fang; Toh, Ying Xiu; Chan, Katherine; Hermida, Lisset; Connolly, John E.; Guillén, Gerardo; Fink, Katja

doi:10.1016/j.vaccine.2015.01.074

Cited by 17 publications

(19 citation statements)

References 42 publications

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“…Specifically, studies with live vaccines have shown that AG129 mice generate protective responses [88][89][90]. However, AG129 mice are lacking aspects of cellular immunity that appear to impact their ability to produce protection following immunization with a non-replicating vaccine [93]. An alternative approach is to use conditional IFNAR −/− knockdowns in dendritic cells or macrophages to study the immune response to a subunit vaccine [66].…”

Section: Discussionmentioning

confidence: 99%

“…Tetravalent dengue EDIIIC is a candidate subunit vaccine composed of recombinant chimeric capsid and E domain III fusion proteins for DENV-1, −2, −3, and −4 and was designed to include both T and B cell epitopes (capsid and E protein, respectively) in the same formulation[93]. Athree-dose immunization regimen of BALB/c and AG129 mice with adjuvanted Tetra DIIIC elicited antibodies specific to the four serotypes.…”

Section: Vaccine Testing In Dengue Mouse Modelsmentioning

confidence: 99%

“…Tetra DIIIC induced a Th1 response andIgG1 and IgG2a against DENV-1–4. These results show that, because IFN-γ is critical for protection for this vaccine candidate, AG129 did not produce neutralizing antibodies [93]. …”

Section: Vaccine Testing In Dengue Mouse Modelsmentioning

confidence: 99%

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Mouse models of dengue virus infection for vaccine testing

Sarathy

Milligan

Bourne

et al. 2015

Vaccine

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Dengue is a mosquito-borne disease caused by four serologically and genetically related viruses termed DENV-1 to DENV-4. With an annual global burden of approximately 390 million infections occurring in the tropics and subtropics worldwide, an effective vaccine to combat dengue is urgently needed. Historically, a major impediment to dengue research has been development of a suitable small animal infection model that mimics the features of human illness in the absence of neurologic disease that was the hallmark of earlier mouse models. Recent advances in immunocompromised murine infection models have resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in AG129 mice that are deficient in both the Interferon-α/β receptor (IFN-α/β R) and the interferon-γ receptor (IFN-γR). These models mimic many hallmark features of dengue disease in humans, such as viremia, thrombocytopenia, vascular leakage, and cytokine storm. Importantly AG129 mice develop lethal, acute, disseminated infection with systemic viral loads, which is characteristic of typical dengue illness. Infected AG129 mice generate an antibody response to DENV, and antibody-dependent enhancement (ADE) models have been established by both passive and maternal transfer of DENV-immune sera. Several steps have been taken to refine DENV mouse models. Viruses generated by peripheral in vivo passages incur substitutions that provide a virulent phenotype using smaller inocula. Because IFN signaling has a major role in immunity to DENV, mice that generate a cellular immune response are desired, but striking the balance between susceptibility to DENV and intact immunity is complicated. Great strides have been made using single-deficient IFN-α/βR mice for DENV-2 infection, and conditional knockdowns may offer additional approaches to provide a panoramic view that includes viral virulence and host immunity. Ultimately, the DENV AG129 mouse models result in reproducible lethality and offer multiple disease parameters to evaluate protection by candidate vaccines.

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Section: Discussionmentioning

confidence: 99%

Section: Vaccine Testing In Dengue Mouse Modelsmentioning

confidence: 99%

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Mouse models of dengue virus infection for vaccine testing

Sarathy

Milligan

Bourne

et al. 2015

Vaccine

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“…A tetravalent vaccine candidate containing the DV2 EDIIIC combined with the EDIII-P64k fusion proteins from DV1, DV3 and DV4 was immunogenic and protected mice against challenge with lethal (DV1, DV2, DV4) or encephalitis-inducing (DV3) virus . Th is formulation was also found to elicit a Th 1-type response and high titers of neutralizing IgG1 and IgG2a antibodies specifi c for the four DV serotypes in mice (Zuest et al, 2015).…”

Section: Domain Iii-dengue Virus Capsid Proteinmentioning

confidence: 94%

“…Tetravalent candidate evaluated in mice; monovalent DV1 and DV2 candidates evaluated in NHPs Hermida et al, 2006;Lazo et al, 2014;Valdés et al, 2009a] EDIII-capsid fusion protein (DIIIC) expressed in E. coli Monovalent DV2 candidate evaluated in NHPs [Gil et al, 2015;Suzarte et al, 2014;Valdés et al, 2009b;Zuest et al, 2015] Tetravalent EDIII-STF2 fusion proteins expressed in E. coli Tetravalent candidate evaluated in mice and NHPs [Liu et al, 2015] EDIII-HBcAg fusion protein expressed in P. pastoris Monovalent DV2 candidate evaluated in mice Recombinant EDII-EDIII-NS1 fusion protein expressed in Drosophila S2 Tetravalent lipidated consensus EDIII (LcED III) expressed in E. coli Tetravalent candidate evaluated in mice [Chen et al, 2013;Chiang et al, 2011;Leng et al, 2009] Lipidated EDIII (LED III) expressed in E. coli Monovalent candidates (DV1,2,4) evaluated in mice [Chiang et al, 2011[Chiang et al, , 2013a MixBiEDIII: bivalent EDIIIs (DV1-2/ DV3-4) expressed in E. coli Tetravalent candidate evaluated in mice [Zhao et al, 2014] Bivalent EDIII (DV1-2) expressed in E. coli Bivalent candidate (DV1-2) evaluated in mice [Zhang et al, 2015] Tetravalent chimeric EDIII expressed in P. pastoris Tetravalent candidate evaluated in mice [Etemad et al, 2008] Non-structural proteins Recombinant DV2 NS1 protein expressed in E. coli Monovalent DV2 candidate evaluated in mice [Amorim et al, 2012] Recombinant DV2 NS1-DEC205 fusion protein expressed in E. coli Monovalent DV2 candidate evaluated in mice [Henriques et al, 2013] Full-length recombinant DV2 NS3 protein expressed in E. coli Monovalent DV2 candidate evaluated in mice [Ramírez et al, 2014] Capsid protein Recombinant capsid protein expressed in E. coli Monovalent DV2 candidate evaluated in mice and NHPs …”

Section: Ediii-p64k Fusion Proteins Expressed In Escherichia Colimentioning

confidence: 99%

Dengue vaccine: an update on recombinant subunit strategies

Martín¹,

Hermida²

2016

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Summary. -Dengue is an increasing public health problem worldwide, with the four serotypes of the virus infecting over 390 million people annually. Th ere is no specifi c treatment or antiviral drug for dengue, and prevention is largely limited to controlling the mosquito vectors or disrupting the human-vector contact. Despite the considerable progress made in recent years, an eff ective vaccine against the virus is not yet available. Th e development of a dengue vaccine has been hampered by many unique challenges, including the need to ensure the absence of vaccine-induced enhanced severity of disease. Recombinant protein subunit vaccines off er a safer alternative to other vaccine approaches. Several subunit vaccine candidates are presently under development, based on diff erent structural and non-structural proteins of the virus. Novel adjuvants or immunopotentiating strategies are also being tested to improve their immunogenicity. Th is review summarizes the current status and development trends of subunit dengue vaccines.

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