VIOLIN Logo
VO Banner
Search: for Help
About
Introduction
Statistics
VIOLIN News
Your VIOLIN
Register or Login
Submission
Tutorial
Vaccine & Components
Vaxquery
Vaxgen
VBLAST
Protegen
VirmugenDB
DNAVaxDB
CanVaxKB
Vaxjo
Vaxvec
Vevax
Huvax
Vaccine Mechanisms
Vaximmutordb
Vaxism
Vaxar
Vaccine Literature
VO-SciMiner
Litesearch
Vaxmesh
Vaxlert
Vaccine Design
Vaxign
Community Efforts
Vaccine Ontology
ICoVax 2012
ICoVax 2013
Advisory Committee
Vaccine Society
Vaxperts
VaxPub
VaxCom
VaxLaw
VaxMedia
VaxMeet
VaxFund
VaxCareer
Data Exchange
V-Utilities
VIOLINML
Help & Documents
Publications
Documents
FAQs
Links
Acknowledgements
Disclaimer
Contact Us
UMMS Logo

Vaccine Detail

LC16m8
Vaccine Information
  • Vaccine Name: LC16m8
  • Target Pathogen: Variola virus
  • Target Disease: Smallpox
  • Vaccine Ontology ID: VO_0004091
  • Type: Attenuated Lister strain
  • A33R from Vaccinia virus (strain: WR (Western Reserve)) gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-A33R; associates with A36R; involved in CEV-cell adherence and actin tail formation (NCBI).
    • Detailed Gene Information: Click Here.
  • A34R gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-A34R; involved in CEV cell adherence and actin tail formation (NCBI).
    • Detailed Gene Information: Click Here.
  • A36R gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-A36R; interacts with A33R and used in actin tail formation (NCBI).
    • Detailed Gene Information: Click Here.
  • A56R gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-A56R; EEV; type-I membrane glycoprotein; inhibits cell fusion (NCBI).
    • Detailed Gene Information: Click Here.
  • A21L gene engineering:
    • Type: Protein
    • Description:
    • Detailed Gene Information: Click Here.
  • B5R from Vaccinia virus (strain: WR (Western Reserve)) gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-B5R; required for trans-Golgi/endosomal membrane-wrapping of IMV (NCBI).
    • Detailed Gene Information: Click Here.
  • F13L gene engineering:
    • Type: Protein
    • Description: Similar to VACCP-F13L; phospholipase motif, required for IEV formation (NCBI).
    • Detailed Gene Information: Click Here.
  • Preparation: Virus suspensions were diluted serially in phosphate-buffered saline (PBS) supplemented with adjuvant and overlaid with a suspension of 1% carboxyl methyl cellulose in DMEM supplemented to contain 5% FBS (Empig et al., 2006).
  • Virulence: RPV is a virulent strain of vaccinia virus that produces high levels of detectable EEV. In infected rabbits, it causes a generalized, disseminated infection, resulting in death in the majority of cases. However, LC16m8, despite the B5R mutation, is equivalent to Dryvax in the capacity to protect rabbits from lethal RPV challenge (Empig et al., 2006).
  • Description: LC16m8 was developed and widely used in Japan prior to the global eradication of smallpox. Numerous preclinical safety studies in several animal species were conducted comparing LC16m8 to the parental strain Lister, each showing that the attenuated vaccinia virus strain, in contrast to Lister, was incapable of invading the central nervous system (CNS). LC16m8 also was not neuroinvasive in cortisone-treated immunocompromised mice. Clinical trials in Japan, in which over 10,000 children received LC16m8, demonstrated enhanced safety of this attenuated vaccine in comparison to Lister, while confirming that its immunogenicity was unaltered (Empig et al., 2006).
Host Response

Mouse Response

  • Host Strain: A/NCR
  • Vaccination Protocol: Three groups of 30 4–6 week old A/NCR mice each were vaccinated at the base of the tail with LC16m8 (approximately 2 × 105 PFU). Forty-one days post-vaccination, sera were collected for assessment of virus-specific antibody responses prior to challenge. Forty-nine days post-vaccination, animals were challenged with ECTV delivered by aerosol. ECTV was suspended in DMEM without FBS and inoculated by using a nose-only inhalation exposure system. The remaining mice were observed for 21 days for signs of disease and mortality. Animals were evaluated daily for weight assessment and clinical symptoms (Empig et al., 2006).
  • Persistence: (Empig et al., 2006)
  • Side Effects: Despite limiting vaccination to healthy individuals in recent vaccination campaigns, adverse reactions were still observed, highlighting the need for a safer yet equally protective alternative to Dryvax. However, no serious adverse reactions, such as encephalitis, were observed during the early use of LC16m8 vaccine (Empig et al., 2006).
  • Efficacy: Mice immunized with LC16m8 were protected against lethal ECTV infection. LC16m8 generated antibody responses in mice that exceeded those generated by Dryvax (Empig et al., 2006).
  • Description: To evaluate the protective efficacy of LC16m8 in comparison to Dryvax, the study employed both rabbit and mouse models of poxvirus disease (Empig et al., 2006).

Rabbit Response

  • Host Strain: New Zeland White (NZW)
  • Vaccination Protocol: Groups of 20 NZW rabbits (10 male and 10 female) were vaccinated with LC16m8 (at approximately 2 × 105 PFU) via scarification to the hind flank. 28 d after vaccination, animals were challenged intradermally with either low (200 PFU) or high (1000 PFU) doses of RPV, which correspond to 1 or 5 times the LD100 value, respectively. Animals were monitored daily for temperature and behavioral changes. Survival was determined at 10 d after RPV challenge, at which time all living rabbits were euthanized (Empig et al., 2006).
  • Persistence: (Empig et al., 2006)
  • Side Effects: A mild inflammatory response was detected over the vaccination site 1–7 d following vaccination with either LC16m8 or Dryvax. The response was characterized by ulceration and erythema, followed by pock formation and a small scar. Despite limiting vaccination to healthy individuals in recent vaccination campaigns, adverse reactions were still observed, highlighting the need for a safer yet equally protective alternative to Dryvax. However, no serious adverse reactions, such as encephalitis, were observed during the early use of LC16m8 vaccine (Empig et al., 2006).
  • Efficacy: Rabbits vaccinated with LC16m8 survived lethal RPV challenge at both challenge doses tested (Empig et al., 2006).
  • Description: To evaluate the protective efficacy of LC16m8 in comparison to Dryvax, the study employed both rabbit and mouse models of poxvirus disease (Empig et al., 2006).
References
Empig et al., 2006: Empig C, Kenner JR, Perret-Gentil M, Youree BE, Bell E, Chen A, Gurwith M, Higgins K, Lock M, Rice AD, Schriewer J, Sinangil F, White E, Buller RM, Dermody TS, Isaacs SN, Moyer RW. Highly attenuated smallpox vaccine protects rabbits and mice against pathogenic orthopoxvirus challenge. Vaccine. 2006 Apr 24; 24(17); 3686-94. [PubMed: 16430997 ].
NCBI: Entrez Gene [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=gene]