LC16m8: An attenuated smallpox vaccine

Abstract

The frequency of moderate to severe adverse reactions associated with smallpox vaccines currently stockpiled in the US, and the continued threat of bioterrorism have prompted the development of effective vaccines with improved safety profiles. LC16m8, an attenuated, replicating smallpox vaccine derived from the Lister strain of vaccinia, is currently licensed in Japan where it was safely used in over 50,000 children in the 1970s. It has been shown to have markedly less neurotoxicity than unattenuated vaccines in nonclinical studies. LC16m8 is immunogenic after a single dose, and recent studies in two different animal models have demonstrated protective efficacy equivalent to that of the only FDA-licensed smallpox vaccine. This article reviews the history and available scientific literature regarding LC16m8 and provides comparisons to other smallpox vaccines.

Evaluating the Orthopoxvirus Type I Interferon-Binding Molecule as a Vaccine Target in the Vaccinia Virus Intranasal Murine Challenge Model

“…Some groups have developed attenuated versions of VACV as safer alternatives. These include MVA and Lc16m8 (13,20,(23)(24)(25). Other groups have developed subunit protein and DNA-based vaccines.…”

Smallpox vaccines: New formulations and revised strategies for vaccination

“…64 LC16m8 is a Japanese vaccine strain originating from an attenuated plaque isolate of the VACV strain Lister. 65 Attenuation was specifically linked to inactivation of the B5R open reading frame resulting in inefficient production of extracellular enveloped virions which represent the form of infectious VACV being considered most important for in vivo dissemination. 66 Unlike MVA, LC16m8 can productively replicate in a broad range of host cells and the genome of the virus does not contain other major alterations in comparison to non-attenuated VACV strains.…”

Postexposure Smallpox Vaccines - Can We Extend the Therapeutic Window?

“…Viruses of the family Poxviridae contain large double-stranded DNA genomes of 53 130,000 to >300,000 nucleotides and infect vertebrate (Chordopoxvirinae) and insect 63 VARV is highly contagious and virulent to humans and the estimated human dose 64 (LD30) is 1-10pfu. The obligatory infection of human hosts together with the efficient genomes encode the broadest set of viral genes that unlike the host restricted members 108 (VARV, CMLV, ECTV) might enable CPXV to more efficiently evade the immune 109 system and to more easily adapt to different species [21][22] .…”

“…Indeed, concerns about the vaccine's efficacy 244 were raised, yet, the data indicates that antibody response generated following 245 vaccination with LC16m8 is capable of neutralizing extracellular virions through 246 antibodies against other EV epitopes, yet at a lower efficiency than antibodies generated 247 following conventional smallpox vaccination [58][59][60] . The efficacy of LC16m8 has been 248 addressed in various animal models indicating that LC16m8 induces robust poxvirus 249 protective immune response equivalent to the conventional vaccines [61][62][63][64] . Unlike MVA,…”