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Research Article Free access | 10.1172/JCI109730

Adverse Effects of Cytomegalovirus Vaccination in Mice

M. Colin Jordan

Division of Infectious Diseases, Department of Medicine, and Reed Neurological Research Center, University of California School of Medicine, Los Angeles, California 90024

Find articles by Jordan, M. in: JCI | PubMed | Google Scholar

Published April 1, 1980 - More info

Published in Volume 65, Issue 4 on April 1, 1980
J Clin Invest. 1980;65(4):798–803. https://doi.org/10.1172/JCI109730.
© 1980 The American Society for Clinical Investigation
Published April 1, 1980 - Version history
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Abstract

Studies of live attenuated cytomegalovirus (CMV) vaccine have recently been initiated in man. The possibilities of latent infection and disease resulting from reactivation of vaccine virus are major concerns. Because markers for attenuation of tissue culture-passaged mouse CMV (MCMV) exist, studies of potential adverse effects of vaccination were initiated in mice. Plaque-purified MCMV was passed 12 times in cell culture (“vaccine virus”) and shown to be attenuated by virtue of loss of lethality and diminished replication in reticuloendothelial organs of normal mice. Although subcutaneous inoculation of 105 plaque-forming units of wild virus was lethal for mice immunosuppressed with antilymphocyte serum (18/18 died), “vaccine MCMV” killed only 3/18 (P < 0.05) and was thus shown to be highly attenuated even in immunosuppressed animals. 4 mo after subcutaneous inoculation of vaccine MCMV, no infectious virus was detectable in the tissues of normal C3H mice. However, immunosuppression with anti-lymphocyte serum and cortisone caused MCMV reactivation, dissemination, and wide-spread cytomegalic inclusion disease in 19 of 20 animals. Characterization of the reactivating virus recovered from salivary glands indicated that reversion to virulence had occurred. Thus, vaccine MCMV, although markedly attenuated initially, established latent infection, reactivated after immunosuppression, and reverted to virulence, at least in salivary gland tissue. These data from the murine model substantiate the need for careful surveillance and virologic study of patients given experimental CMV vaccine.

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