Vaccinia Virus LC16m8∆ as a Vaccine Vector for Clinical Applications

Vaccines
Minoru Kidokoro, Hisatoshi Shida

Abstract

The LC16m8 strain of vaccinia virus, the active ingredient in the Japanese smallpox vaccine, was derived from the Lister/Elstree strain. LC16m8 is replication-competent and has been administered to over 100,000 infants and 3,000 adults with no serious adverse reactions. Despite this outstanding safety profile, the occurrence of spontaneously-generated large plaque-forming virulent LC16m8 revertants following passage in cell culture is a major drawback. We identified the gene responsible for the reversion and deleted the gene (B5R) from LC16m8 to derive LC16m8Δ. LC16m8∆ is non-pathogenic in immunodeficient severe combined immunodeficiency (SCID) mice, genetically-stable and does not reverse to a large-plaque phenotype upon passage in cell culture, even under conditions in which most LC16m8 populations are replaced by revertants. Moreover, LC16m8∆ is >500-fold more effective than the non-replicating vaccinia virus (VV), Modified Vaccinia Ankara (MVA), at inducing murine immune responses against pathogenic VV. LC16m8∆, which expresses the SIV gag gene, also induced anti-Gag CD8⁺ T-cells more efficiently than MVA and another non-replicating VV, Dairen I minute-pock variants (DIs). Moreover, LC16m8∆ expressing HIV-1 Env in combinati...Continue Reading

References

May 1, 1992·Virology·J TartagliaM Riviere
Nov 1, 1990·Virology·M E PerkusE Paoletti
Nov 1, 1990·The Journal of General Virology·J D WilliamsonM Mackett
Mar 1, 1985·The Journal of General Virology·L G Payne, K Kristensson
Oct 1, 1980·The Journal of Infectious Diseases·P F Wehrle
May 31, 1995·Annals of the New York Academy of Sciences·M E PerkusE Paoletti
Jun 15, 1999·JAMA : the Journal of the American Medical Association·D A HendersonK Tonat
Jul 27, 2001·The Journal of Cell Biology·M HollinsheadG L Smith
Dec 6, 2002·The Journal of General Virology·Geoffrey L SmithMansun Law
Jun 24, 2003·Comparative Immunology, Microbiology and Infectious Diseases·Anton Mayr
Aug 20, 2003·Nature Medicine·Richard WeltzinThomas P Monath
Jan 23, 2004·The New England Journal of Medicine·Kurt D ReedInger K Damon
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Linda S WyattBernard Moss
Apr 14, 2004·Journal of Virology·J W HooperP B Jahrling
Jun 24, 2004·The Journal of Experimental Medicine·Tetsuro MatanoYoshiyuki Nagai
Oct 20, 2004·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Thomas P MonathRichard Weltzin
Mar 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Minoru KidokoroHisatoshi Shida
May 28, 2005·Journal of Virology·Koert J StittelaarAlbert D M E Osterhaus
Jul 19, 2005·Emerging Infectious Diseases·Frederick A Murphy, Bennie I Osburn

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.