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Vaccines

Novel Low-Cost Vaccines for Rabies Show Promise in Research

Strategic Insights

— 1 min read

Researchers at the University of Oxford have made a breakthrough in developing low-cost vaccines for rabies, a potentially deadly disease caused by the rabies virus. The current vaccines require multiple doses and are relatively expensive, limiting their accessibility. The new research focused on creating novel vaccines that can induce a protective antibody response against the rabies virus glycoprotein.

Key Takeaways:

  • The current rabies vaccines are relatively expensive and require multiple doses, limiting their accessibility.
  • Researchers at the University of Oxford investigated the potential of structure-guided engineering of the antigen and transgene cassette optimisation for the design of improved rabies vaccines.
  • The study evaluated twelve candidate cassette designs and found that codon optimisation enhanced expression in vitro but did not translate into improved immunogenicity.
  • Co-expression of the rabies virus glycoprotein (RVG) with rabies matrix protein (RVM) did not detectably affect expression or immunogenicity.
  • Inserting a C-terminal trimerisation domain was detrimental to expression in vitro and did not improve immunogenicity compared to the wild-type comparator.
  • The researchers screened 72 mutant constructs for in vitro expression and pre-fusion stabilisation, finding several mutants that enhanced expression and/or pre-fusion stability at low pH.
  • A combination of the previously reported H270P mutation with the H419L substitution achieved enhanced stability, and an L271Q + H419L double mutant achieved the greatest positive effect upon expression.
  • However, neither of the double mutants improved immunogenicity compared to wild-type RVG when tested using an mRNA vaccine platform.

Statistics:

  • 72 mutant constructs were screened for in vitro expression and pre-fusion stabilisation.
  • 12 candidate cassette designs were evaluated in the study.
  • 7 of the 72 mutant constructs enhanced expression and/or pre-fusion stability at low pH, including a combination of the H270P mutation and the H419L substitution.
  • The L271Q + H419L double mutant achieved the greatest positive effect upon expression.

Sources:

  • Rabies glycoprotein engineering for improved stability and expression. Vaccine, 2025;62:127541.
  • NewsRx. Researchers from University of Oxford Describe Findings in Rabies Virus (Rabies glycoprotein engineering for improved stability and expression). Vaccine Weekly. August 13, 2025; p 6938.

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