Induction of robust immunity by the emulsification of recombinant lipidated dengue-1 envelope protein domain III

Background: The emergence of Zika virus (ZV) in tropical and subtropical areas of the world has created an urgent need for vaccines against ZV. However, approved vaccines that prevent ZV infection are not available. To develop an effective vaccine against ZV infection, a lipidated form of ZV envelope protein domain III that possesses an intrinsic adjuvant property was rationally designed. Our goal was to examine the immunogenicity of recombinant lipidated ZV envelope protein domain III (rLZE3) and evaluate its potential as a vaccine candidate against ZV.Methods: Recombinant ZV envelope protein domain III (rZE3) and rLZE3 were prepared with an Escherichia colibased system. Dendritic cell surface marker expression and cytokine production upon stimulation were analyzed to evaluate the function of rLZE3. Neutralizing antibody capacities were evaluated using focus reduction neutralization tests after immunization. To investigate the protective immunity in immunized mice, serum samples collected from immunized mice were adoptively transferred into AG129 mice, and then viremia levels and survival times were examined after ZV challenge.Results: rLZE3 alone but not rZE3 alone efficiently activated dendritic cells in vitro and was taken up by dendritic cells in vivo. Immunization of C57BL/6 mice with rLZE3 alone (without exogenous adjuvant) could induce ZVspecific neutralizing antibody responses. Furthermore, serum samples obtained from rLZE3-immunized mice provided protection as indicated by a reduction in viremia levels and prolongation of survival times after ZV challenge. Conclusion: These results indicate that rLZE3 is an excellent vaccine candidate and has great potential that should be evaluated in further preclinical studies.

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“…1g). These peaks are considered to be lipidation signatures that have been confirmed in other recombinant lipidated proteins [16,18,19,22].…”

Section: Preparation and Characterization Of Recombinant Zika Virus Ementioning

confidence: 87%

“…Envelope protein domain III (E3) of dengue virus contains an immunoglobulin-like fold and contributes to viral attachment [13,14]. Our previous studies have shown that E3 of dengue virus is a potential dengue vaccine candidate [15][16][17][18][19][20][21][22][23]. It is very likely that antibodies against ZV E3 can neutralize ZV infection.…”

Section: Introductionmentioning

confidence: 99%

Recombinant lipidated Zika virus envelope protein domain III elicits durable neutralizing antibody responses against Zika virus in mice

et al. 2020

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“…We demonstrated that Escherichia coli -expressed lipoprotein stimulated innate immunity through the toll-like receptor 2 36 and induced superior adaptive immunity to its non-lipidated counterpart 35 37 . This lipidation approach has been applied to each serotype of ED III 38 39 40 41 , but a tetravalent formulation has not yet been characterized. In the present study, we further analyzed the profiles of T-cell epitopes and antibody responses in mice after immunization with tetravalent lipidated ED III (tLED III).…”

mentioning

confidence: 99%

Immunogenicity of a novel tetravalent vaccine formulation with four recombinant lipidated dengue envelope protein domain IIIs in mice

Chiang

Pan

Chen

et al. 2016

Sci Rep

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We developed a novel platform to express high levels of recombinant lipoproteins with intrinsic adjuvant properties. Based on this technology, our group developed recombinant lipidated dengue envelope protein domain IIIs as vaccine candidates against dengue virus. This work aims to evaluate the immune responses in mice to the tetravalent formulation. We demonstrate that 4 serotypes of recombinant lipidated dengue envelope protein domain III induced both humoral and cellular immunity against all 4 serotypes of dengue virus on the mixture that formed the tetravalent formulation. Importantly, the immune responses induced by the tetravalent formulation in the absence of the exogenous adjuvant were functional in clearing the 4 serotypes of dengue virus in vivo. We affirm that the tetravalent formulation of recombinant lipidated dengue envelope protein domain III is a potential vaccine candidate against dengue virus and suggest further detailed studies of this formulation in nonhuman primates.

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“…In addition, sera from LD2ED III-immunized animals had reduced ADE activity when compared to those from animals immunized with DV2. Th e LD1ED III vaccine candidate induced up-regulation of activation markers and IL-6 production on RAW 264.7 macrophage cells (Chiang et al, 2013b). Immunization of mice with LD1ED III elicited a long-lasting neutralizing antibody response that was increased when the protein was combined with a water-in-oil-in-water nanoemulsion containing a bioresorbable polymer, Span®85, and squalene.…”

Section: Lipidated Domain IIImentioning

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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Induction of robust immunity by the emulsification of recombinant lipidated dengue-1 envelope protein domain III

Cited by 17 publications

References 44 publications

Recombinant lipidated Zika virus envelope protein domain III elicits durable neutralizing antibody responses against Zika virus in mice

Recombinant lipidated Zika virus envelope protein domain III elicits durable neutralizing antibody responses against Zika virus in mice

Immunogenicity of a novel tetravalent vaccine formulation with four recombinant lipidated dengue envelope protein domain IIIs in mice

Dengue vaccine: an update on recombinant subunit strategies

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