Page 44
allied
academies
J u n e 2 8 - 2 9 , 2 0 1 8 | A m s t e r d a m , N e t h e r l a n d s
Joint Event on
OBESITY AND WEIGHT MANAGEMENT
VACCINES AND IMMUNOLOGY
&
International Conference on
International Conference on
Asian Journal of Biomedical and Pharmaceutical Sciences
|
Volume 8
ISSN:
2249-622X
Asian J Biomed Pharmaceut Sci 2018, Volume 8 | DOI: 10.4066/2249-622X-C1-003
STRATEGIES FOR ENHANCING THE SAFETY AND EFFICACY OF
LIVE RECOMBINANT VACCINES
Tilahun Yilma
University of California, USA
W
e have taken several approaches to improve the safety and efficacy of recombinant vaccines for use in humans and
animals, including: choice of the strain of vaccinia virus (VACV) used as a vector, insertional inactivation of virulence and
immunoregulatory genes of VACV, and expression of cytokine genes that attenuate the vector by more than a million-fold without
reduction in immunogenicity. These strategies are illustrated by providing examples of recombinant VACV (rVACV) vaccines we
have developed for rinderpest, vesicular stomatitis, simian immunodeficiency virus, smallpox, and Rift Valley fever. Additionally,
we have exploited the advantages of recombinant vaccines and developed diagnostic kits that permit one to distinguish between
vaccinated and infected individuals. We constructed rVACVs expressing an interferon gamma (IFNγ) and lacking the immune-
modulating genes
B8R, B13R
and
B22R
. IFNγ is a cytokine with potent immunoregulatory, antineoplastic, and antiviral properties.
These rVACVs replicated to high titers in tissue culture yet were avirulent in both immunocompromised and immunocompetent
mice with no detectable viral replication in these animals. A single immunization elicited potent humoral, T-helper, and cytotoxic
T-cell immune responses in mice despite the absence of any detectable virus replication
in vivo
. IFNγ co-expression and the
inactivation of one or more VACV immune-modulating genes provide an optimized method for increasing the safety while
maintaining the efficacy of rVACV vaccines for use in humans and animals.
tdyilma@ucdavis.edu