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Poxvirus deletion mutants: virulence and immunogenicity.
K M Edwards1, T C Andrews, J Van Savage
1Department of Pediatrics, Vanderbilt University, Nashville, Tennessee 37232.
Microbial Pathogenesis
|May 1, 1988
Summary
New rabbitpox virus (RPV) deletion mutants show reduced invasiveness and neurovirulence. These attenuated poxvirus vectors demonstrate potential for developing safer vaccinia virus vaccine vectors.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Vaccinia virus recombinants are used as immunization vectors.
- Post-vaccinial encephalitis and disseminated vaccinia are significant safety concerns.
Purpose of the Study:
- To identify and characterize attenuated poxvirus vectors.
- To evaluate rabbitpox virus (RPV) and its deletion mutants for organ tropism, neurovirulence, and protective efficacy.
Main Methods:
- Intraperitoneal (IP) and intracerebral (IC) inoculation of BALB/c mice with wild-type (wt) RPV and deletion mutants.
- Assessing viral titers in organs, lethal dose 50% (LD50) for neurovirulence, and protection against wt RPV challenge after scarification immunization.
Main Results:
- Mutants 31 and 23 (approx. 30 kb deletions) showed markedly reduced viral growth in organs compared to wt RPV and mutants 8 sm/28 (approx. 12 kb deletions).
- Mutants 31 and 23 exhibited significantly lower neurovirulence (LD50 > 10^5 PFU) than wt RPV and mutants 8 sm/28 (LD50 < 10^2 PFU).
- Scarification with mutants 31 or 23 induced local skin growth and protected mice against lethal IC challenge with wt RPV.
Conclusions:
- RPV deletion mutants 31 and 23 are significantly less invasive and neurovirulent.
- These mutants retain immunogenicity, offering protection against wild-type RPV challenge.
- Similar deletion strategies in vaccinia virus could yield avirulent yet effective vaccine vectors for human use.