Distinct neutralizing antibody response elicited by Zika virus nanoparticle vaccines Ping-Han Huang1, Hsiao-Han Tsai1, Che-Ming Hu2, Hui-Wen Chen1* 1Department of Veterinary Medicine, National Taiwan University, Taiwan 2Institute of Biomedical Sciences, Academia Sinica, Taiwan *Corresponding author
Zika virus (ZIKV), a mosquito-transmitted flavivirus, was recently found to be correlated with birth defects such as microcephaly and Guillain-Barré syndrome during a 2015 outbreak in the Americas and the Caribbean. An effective ZIKV vaccine is needed to protect pregnant women and their fetuses. ZIKV envelope (E) protein is responsible for virus entry and considered to be a primary target for vaccine design. E protein epitopes including fusion loop, E protein domain III and E dimer region were found to elicit potent virus-neutralizing antibodies. In this study, we sought to develop an E protein-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) vaccine against ZIKV. We also proceeded to compare the effects on E antigen loading by two protein coating methods. The first method used poly-dopamine (PD) as the linker to conjugate E protein with the PLGA NP base. The second method deployed a reductant, tris(2-carboxyethyl)phosphine (TCEP), to reduce the disulfide bonds of E protein to thiol form and enhance protein-particle covalently conjugation. Immunogenicity of each particle vaccine was assessed in C57BL/6 mice. Serum was evaluated for E protein specific antibody titer by enzyme-linked immunosorbent assay (ELISA) and neutralizing activity by plaque reduction neutralization test (PRNT). Vaccination with either NP vaccine elicited the similar titer of E protein specific antibody. However, mice receiving the E protein coated-PD PLGA NP vaccine or E protein coated-maleimide-PLGA NP vaccine had the different serum neutralizing response against ZIKV, with reciprocal dilution EC50 values of 50 or 5, separately. Our data suggested that method for E protein coating affects vaccine performance dramatically. Further studies will be conducted to improve the efficacy of NP vaccine and characterize the effect of this vaccine on ZIKV infection.
This study was supported by NHRI-EX107-10721SC from National Health Research Institutes, Taiwan.
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