title: Safety and immunogenicity of LC16m8, an attenuated smallpox vaccine in vaccinia-naive adults.
abstract: BACKGROUND
  LC16m8 is an attenuated cell culture-adapted Lister vaccinia smallpox vaccine missing the B5R protein and licensed for use in Japan.
  
  
  METHODS
  We conducted a phase I/II clinical trial that compared the safety and immunogenicity of LC16m8 with Dryvax in vaccinia-naive participants. Adverse events were assessed, as were electrocardiography and laboratory testing for cardiotoxicity and viral culturing of the vaccination sites. Neutralization titers to vaccinia, monkeypox, and variola major were assessed and cell-mediated immune responses were measured by interferon (IFN)-γ enzyme-linked immunosorbent spot and lymphoproliferation assays.
  
  
  RESULTS
  Local and systemic reactions after vaccination with LC16m8 were similar to those reported after Dryvax. No clinically significant abnormalities consistent with cardiac toxicity were seen for either vaccine. Both vaccines achieved antivaccinia, antivariola, and antimonkeypox neutralizing antibody titers >1:40, although the mean plaque reduction neutralization titer of LC16m8 at day 30 after vaccination was significantly lower than Dryvax for anti-NYCBH vaccinia (P < .01), antimonkeypox (P < .001), and antivariola (P < .001). LC16m8 produced robust cellular immune responses that trended higher than Dryvax for lymphoproliferation (P = .06), but lower for IFN-γ ELISPOT (P = .02).
  
  
  CONCLUSIONS
  LC16m8 generates neutralizing antibody titers to multiple poxviruses, including vaccinia, monkeypox, and variola major, and broad T-cell responses, indicating that LC16m8 may have efficacy in protecting individuals from smallpox. Clinical Trials Registration. NCT00103584.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Kennedy
authors.forename: Marc
authors.initials: M
authors.lastname: Gurwith
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Edwards
authors.forename: Julie
authors.initials: J
authors.lastname: Kenner
authors.forename: Michael
authors.initials: M
authors.lastname: Lock
authors.forename: Cyril
authors.initials: C
authors.lastname: Empig
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morikawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saijo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yokote
authors.forename: Kevin
authors.initials: K
authors.lastname: Karem
authors.forename: Inger
authors.initials: I
authors.lastname: Damon
authors.forename: Mark
authors.initials: M
authors.lastname: Perlroth
authors.forename: Richard N
authors.initials: RN
authors.lastname: Greenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007564:Japan; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008993:Monkeypox virus / Q000276:immunology; D012899:Smallpox / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000009:adverse effects* / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D012901:Variola virus / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated