Abstract

Chikungunya fever is an acute infectious disease that is mediated by the mosquito-transmitted chikungunya virus (CHIKV), for which no licensed vaccines are currently available. Here, we explored several immunization protocols and investigated their immunity and protective effects in mice, with DNA- and virus-like particle (VLP)- vaccines, both alone and in combination. Both DNA and VLP vaccine candidates were developed and characterized, which express CHIKV structural genes (C-E3-E2-6K-E1). Mice were immunized twice, with different protocols, followed by immunological detection and CHIKV Ross challenge. The highest antigen-specific IgG and neutralizing activity were induced by DNA and VLP co-immunization, while the highest cellular immunity was induced by DNA vaccination alone. Although all vaccine groups could protect mice from lethal CHIKV challenge, demonstrated as reduced viral load in various tissues, without weight loss, mice co-immunized with DNA and VLP exhibited the mildest histopathological changes and lowest International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) scores, in comparison to mice with either DNA or VLP vaccination alone. We concluded that co-immunization with DNA and VLP is a promising strategy to inducing better protective immunity against CHIKV infection.

Highlights

  • Chikungunya fever (CHIKF) is a recurrent infectious disease caused by the chikungunya virus (CHIKV), which belongs to the genus Alphavirus of the Togaviridae family [1, 2]

  • We developed novel CHIKV DNA and virus-like particle (VLP) vaccines, and evaluated their immunological and protective effects in mice, using different vaccination protocols

  • Co-immunization of mice with DNA and VLP vaccines exhibited the mildest histopathological changes and lowest International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) scores, in comparison to mice with either DNA or VLP vaccination alone. This promising protection observed in mice co-immunized with DNA and VLP vaccines may be associated with higher levels of humoral immunity (IgG and neutralizing antibodies)

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Summary

Introduction

Chikungunya fever (CHIKF) is a recurrent infectious disease caused by the chikungunya virus (CHIKV), which belongs to the genus Alphavirus of the Togaviridae family [1, 2]. First documented in Tanzania in 1952, this virus has caused several CHIKF outbreaks, mainly in Africa and Asia. Widespread outbreak of CHIKF in recent years has made it a global public health problem [3]. CHIKV is a positive-stranded RNA virus that encodes six structural (C-E3-E2-6K/TF-E1) and four non-structural (nsP1, helicase nsP2, nsP3, and polymerase nsP4) proteins [4]. The two alphavirus envelope glycoproteins E1 and E2, each containing a single transmembrane domain, are responsible for mediating viral attachment (E2) and membrane fusion (E1) [5, 6]. The prefusion E1/E2 heterodimer is arranged in 80 trimeric spikes, resulting in a viral particle with an icosahedral structure [7, 8]

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