Vaccination of Mice Using the West Nile Virus E-Protein in a DNA Prime-Protein Boost Strategy Stimulates Cell-Mediated Immunity and Protects Mice against a Lethal Challenge

Abstract

West Nile virus (WNV) is a mosquito-borne flavivirus that is endemic in Africa, the Middle East, Europe and the United States. There is currently no antiviral treatment or human vaccine available to treat or prevent WNV infection. DNA plasmid-based vaccines represent a new approach for controlling infectious diseases. In rodents, DNA vaccines have been shown to induce B cell and cytotoxic T cell responses and protect against a wide range of infections. In this study, we formulated a plasmid DNA vector expressing the ectodomain of the E-protein of WNV into nanoparticles by using linear polyethyleneimine (lPEI) covalently bound to mannose and examined the potential of this vaccine to protect against lethal WNV infection in mice. Mice were immunized twice (prime – boost regime) with the WNV DNA vaccine formulated with lPEI-mannose using different administration routes (intramuscular, intradermal and topical). In parallel a heterologous boost with purified recombinant WNV envelope (E) protein was evaluated. While no significant E-protein specific humoral response was generated after DNA immunization, protein boosting of DNA-primed mice resulted in a marked increase in total neutralizing antibody titer. In addition, E-specific IL-4 T-cell immune responses were detected by ELISPOT after protein boost and CD8+ specific IFN-γ expression was observed by flow cytometry. Challenge experiments using the heterologous immunization regime revealed protective immunity to homologous and virulent WNV infection.

Rational Design of Peptide Vaccines for the Highly Lethal Nipah and Hendra Viruses

“…The epitopes determined above are linear epitopes. It is known that viral epitopes are generally conformational; e.g., the West Nile virus epitopes are mostly non-linear and conformational as determined in mice models [37]. For Nipah and Hendra virus we also determine the binding affinities for conformational epitopes, through an Ellipro analysis of IEDB on the whole protein using the 2VWD Protein Data Bank data to determine presence of discontinuous epitopes for B-cell.…”

The challenge of West Nile virus in Europe: knowledge gaps and research priorities

“…Several platforms have been used to develop candidate vaccines against WNV for humans [109]. Various vaccine candidates have been shown to be highly effective in preventing fatal disease in mice and horses [110][111][112]. Long-term immunogenicity and safety, however, are some of the most important problems in current veterinary vaccines against WNV and potential candidates for use in humans.…”

Cross-reactivity reduced dengue virus serotype 2 vaccine does not confer cross-protection against other serotypes of dengue viruses

“…However, DNA 86 vaccines elicit low neutralizing antibodies than protein-based vaccines due to unsatisfactory 87 uptake by host cells and inadequate antigen expression. This was overcome by heterologous 88 prime-boost immunizations, with combined use of DNA and other vaccine formats, which 89 effectively induce a more robust and durable immune response against a number of medically 90 important viruses including HIV [12], influenza [13,14], HCV [15], and flaviviruses [16][17][18][19][20][21][22]. 91 DENV infection elicits a poor quality of immune response that is highly skewed in the 92 production of immunodominant antibodies against cross-reactive poorly neutralizing epitopes 93 in E protein ectodomain II fusion peptide (EDII FP ) [23,24].…”