Influence of adjuvant type and route of administration on the immunogenicity of Leishmania-derived tick-borne encephalitis virus-like particles - A recombinant vaccine candidate

Antiviral Res. 2024 Aug:228:105941. doi: 10.1016/j.antiviral.2024.105941. Epub 2024 Jun 19.

Abstract

Tick-borne encephalitis virus (TBEV) is a tick-borne flavivirus that induces severe central nervous system disorders. It has recently raised concerns due to an expanding geographical range and increasing infection rates. Existing vaccines, though effective, face low coverage rates in numerous TBEV endemic regions. Our previous work demonstrated the immunogenicity and full protection afforded by a TBEV vaccine based on virus-like particles (VLPs) produced in Leishmania tarentolae cells in immunization studies in a mouse model. In the present study, we explored the impact of adjuvants (AddaS03™, Alhydrogel®+MPLA) and administration routes (subcutaneous, intramuscular) on the immune response. Adjuvanted groups exhibited significantly enhanced antibody responses, higher avidity, and more balanced Th1/Th2 response. IFN-γ responses depended on the adjuvant type, while antibody levels were influenced by both adjuvant and administration routes. The combination of Leishmania-derived TBEV VLPs with Alhydrogel® and MPLA via intramuscular administration emerged as a highly promising prophylactic vaccine candidate, eliciting a robust, balanced immune response with substantial neutralization potential.

Keywords: Adjuvants; Leishmania tarentolae; Tick-borne encephalitis virus; Vaccine; Virus-like particles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic* / administration & dosage
  • Adjuvants, Vaccine / administration & dosage
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Encephalitis Viruses, Tick-Borne* / immunology
  • Encephalitis, Tick-Borne* / immunology
  • Encephalitis, Tick-Borne* / prevention & control
  • Female
  • Immunogenicity, Vaccine
  • Injections, Intramuscular
  • Interferon-gamma / immunology
  • Leishmania* / immunology
  • Mice
  • Mice, Inbred BALB C
  • Th1 Cells / immunology
  • Vaccines, Synthetic* / administration & dosage
  • Vaccines, Synthetic* / immunology
  • Vaccines, Virus-Like Particle* / administration & dosage
  • Vaccines, Virus-Like Particle* / immunology
  • Viral Vaccines* / administration & dosage
  • Viral Vaccines* / immunology

Substances

  • Antibodies, Viral
  • Adjuvants, Immunologic
  • Vaccines, Synthetic
  • Viral Vaccines
  • Vaccines, Virus-Like Particle
  • Adjuvants, Vaccine
  • Antibodies, Neutralizing
  • Interferon-gamma