Measles Vaccines Designed for Enhanced CD8⁺ T Cell Activation

Area of Science:

• Immunology
• Vaccinology
• Virology
• Oncolytic Virotherapy

Background:

• CD8+ T cell responses are critical for anti-viral and anti-tumor immunity.
• Live attenuated measles virus vaccines are established and explored for oncolytic virotherapy.
• Reverse genetics allows engineering measles virus vectors to express foreign antigens.

Purpose of the Study:

• To design and evaluate recombinant measles virus vaccine vectors for priming and activating antigen-specific CD8+ T cells.
• To investigate the impact of antigen expression strategies (full-length, epitope, secretion, proteasomal targeting) on T cell activation.

Main Methods:

• Generation of recombinant measles virus vectors expressing tyrosinase-related protein-2 (TRP-2) or ovalbumin (OVA) epitopes.
• In vitro assessment of MHC class I-restricted epitope presentation and activation of cognate cytotoxic T lymphocytes (CTLs).
• Measurement of interferon-gamma (IFNγ) secretion as a marker of T cell activation.
• In vitro priming of naïve OT-I CD8+ T cells by dendritic cells using recombinant OVA vaccines.

Main Results:

• Recombinant measles virus vectors successfully presented epitopes and activated antigen-specific CD8+ T cells in vitro.
• Secreted epitope variants and variants targeted for proteasomal degradation showed enhanced IFNγ release.
• Recombinant OVA vaccines demonstrated the capacity to prime naïve CD8+ T cells.

Conclusions:

• Engineered measles virus vectors can effectively prime and activate antigen-specific CD8+ T cells.
• Strategies enhancing epitope presentation, such as secretion or proteasomal targeting, can boost T cell responses.
• These findings support the development of recombinant measles vaccines for eliciting robust CD8+ T cell immunity against pathogens and tumors.