IMMUNOMODULATION USING TOLL LIKE RECEPTOR (TLR) AGONISTS IMPROVE POSTEXPOSURE VACCINATION EFFICACY OF LIVE SMALLPOX VACCINES

Eradication of Smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release.

Intranasal infection of mice with ectromelia virus (ECTV), a model for human smallpox, is curable by vaccination given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mice were vaccinated postexposure with smallpox vaccine in conjunction with TLR agonists. We show that co-administration of the TLR3 agonist poly(I:C) even 5 days postexposure conferred protection Efficacious treatments prevented death, ameliorated disease symptoms, reduced viral load and maintained tissue integrity at target organs. Protection was associated with significant immune modulation.

The therapeutic potential of postexposure immune modulation by TLR activation opens new directions for the therapy of viral diseases.