Safety of attenuated smallpox vaccine LC16m8 in immunodeficient mice

Hiroyuki Yokote, Yasuhiko Shinmura, Tomomi Kanehara, Shinichi Maruno, Masahiko Kuranaga, Hajime Matsui, So Hashizume, Hiroyuki Yokote, Yasuhiko Shinmura, Tomomi Kanehara, Shinichi Maruno, Masahiko Kuranaga, Hajime Matsui, So Hashizume

Abstract

Freeze-dried live attenuated smallpox vaccine LC16m8 prepared in cell culture has been the sole smallpox vaccine licensed in Japan since 1975 and was recently recommended as a WHO stockpile vaccine. We evaluated the safety of recently remanufactured lots of LC16m8 using a series of immunodeficient mouse models. These models included suckling mice, severe combined immunodeficiency disease (SCID) mice, and wild-type mice treated with cyclosporine. LC16m8 showed extremely low virulence in each of the three mouse models compared with that of its parental strains, Lister and LC16mO. These results provide further evidence that LC16m8 is one of the safest replication-competent smallpox vaccines in the world and may be considered for use in immunodeficient patients.

Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Figures

FIG 1
FIG 1
Effects of vaccination with Lister, LC16mO, or LC16m8 vaccine on ICR suckling mice. Each vaccine was inoculated intracerebrally (see details in the text). The numbers in parentheses shows the number of animals in each experimental group.
FIG 2
FIG 2
Effects of vaccination with Lister, LC16mO, or LC16m8 vaccine on SCID mice. Each vaccine was inoculated intraperitoneally (see details in the text). The numbers in parentheses show the numbers of animals in each experimental group. (A) Survival curve; (B) changes in body weight shown as percentages; (C) clinical score.
FIG 3
FIG 3
Effects of cyclosporine (CsA) on wild-type mice inoculated with Lister or LC16m8 vaccine. The numbers in parentheses show the numbers of animal of each experimental group. Mice were subcutaneously injected with CsA. Mice not receiving injection with CsA were used as controls (see details in the text). The numbers in parentheses show the numbers of animal of each experimental group. (A) Change in immunocyte numbers in mice after treatment with two different doses of CsA compared with those in untreated mice; in this case mice were not inoculated with any vaccine. (B) Clinical scores of the mice inoculated with LC16m8 or Lister vaccine and treated with CsA before or after vaccine inoculation.

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