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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