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

Abstract

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.

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

“…CD8 + T‐cell responses (particularly of a polyfunctional phenotype) are generally thought to play an important role in controlling infection and thus the severity of the disease, partly supported by experimental evidence (Gil et al ., , ; Yauch et al ., ). Although nonstructural proteins are the dominant targets of the CD8 + T‐cell responses (Weiskopf et al ., ), some CD8 + T‐cell epitopes are present in DIII of the envelope protein (Chiang et al ., ; Weiskopf et al ., ). In our studies, we detected cEDIII‐specific both CD4 + and CD8 + T‐cell proliferation in tonsillar cell populations stimulated in vitro .…”

“…Several promising nonlive subunit dengue vaccine candidates have been reported, including DNA vaccines (Poggianella et al, 2015;Porter and Raviprakash, 2015), nanoparticle formulations (Swaminathan et al, 2016) and lipidated dengue antigens (Chiang et al, 2016). These and other preclinical candidates currently being considered are necessary for continuous feeding of the dengue vaccine pipeline until an effective vaccine strategy against this global pandemic is finally attained.…”

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

“…Anti-rZE3 IgG titers in the serum were determined by titration as previously described with some modifications [21]. Serum samples were prepared in 3-fold serial dilutions (starting at 1:30) and then added to rZE3-coated 96-well plates.…”

“…Plasma samples from challenged mice were diluted using 10-fold serial dilutions (starting at 1:10). Virus titers were determined as previously described with some modifications [21]. Diluted plasma was allowed to infect a monolayer of Vero cells in 24-well plates at 37°C.…”

“…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.…”