A single dose recombinant AAV based CHIKV vaccine elicits robust and durable protective antibody responses in mice

PLoS Negl Trop Dis. 2024 Nov 4;18(11):e0012604. doi: 10.1371/journal.pntd.0012604. eCollection 2024 Nov.

Abstract

Background: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is responsible for Chikungunya fever, which is characterized by fever, rash, and debilitating polyarthralgia. Since its re-emergence in 2004, CHIKV has continued to spread to new regions and become a severe health threat to global public. Development of safe and single dose vaccines that provide durable protection is desirable to control the spread of virus. The recombinant adeno-associated virus (rAAV) vectors represent promising vaccine platform to provide prolonged protection with a single-dose immunization. In this study, we developed a rAAV capsid serotype 1 vector based CHIKV vaccine and evaluated its protection effect against CHIKV challenge.

Methodology: The recombinant AAV1 encoding the full-length structural proteins of CHIKV (named as rAAV1-CHIKV-SP) was generated in vitro by transfecting the plasmids of AAV helper-free system into HEK-293T cells. The safety and immunogenicity of rAAV1-CHIKV-SP were tested in 4-week-old C57BL/6 mice. The antibody responses of the mice receiving prime-boost or single-dose immunization of the vaccine were determined by ELISA and plaque reduction neutralizing test. The immunized mice were challenged with CHIKV to evaluate the protection effect of the vaccine.

Conclusions: The rAAV1-CHIKV-SP showed remarkable safety and immunogenicity in C57BL/6 mice. A single dose intramuscular injection of rAAV1-CHIKV-SP elicited high level and long-lasting antibody responses, and conferred complete protection against a heterologous CHIKV strain challenge. These results suggest rAAV1-CHIKV-SP represents a promising vaccine candidate against different CHIKV clades with a simplified immunization strategy.

MeSH terms

  • Animals
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Chikungunya Fever* / immunology
  • Chikungunya Fever* / prevention & control
  • Chikungunya virus* / genetics
  • Chikungunya virus* / immunology
  • Dependovirus* / genetics
  • Dependovirus* / immunology
  • Female
  • Genetic Vectors
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Vaccines* / administration & dosage
  • Viral Vaccines* / genetics
  • Viral Vaccines* / immunology

Substances

  • Antibodies, Viral
  • Viral Vaccines
  • Antibodies, Neutralizing
  • Vaccines, Synthetic

Grants and funding

This work was supported by the Key R&D Program of Hubei Jiangxia Laboratory (NO. JXBS018 to B.Z.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.