Genomic sequence of a clonal isolate of the vaccinia virus Lister strain employed for smallpox vaccination in France and its comparison to other orthopoxviruses

Abstract

Since 1980 there has been global eradication of smallpox due to the success of the vaccination programme using vaccinia virus (VACV). During the eradication period, distinct VACV strains circulated, the Lister strain being the most commonly employed in Europe. Analysis of the safety of smallpox vaccines has suggested that they display significant heterogeneity. To gain a more detailed understanding of the diversity of VACV strains it is important to determine their genomic sequences. Although the sequences of three isolates of the Japanese Lister original strain (VACV-LO) are available, no analysis of the relationship of any Lister sequence compared to other VACV genomes has been reported. Here, we describe the sequence of a representative clonal isolate of the Lister vaccine (VACV-List) used to inoculate the French population. The coding capacity of VACV-List was compared to other VACV strains. The 201 open reading frames (ORFs) were annotated in the VACV-List genome based on protein size, genomic localization and prior characterization of many ORFs. Eleven ORFs were recognized as pseudogenes as they were truncated or fragmented counterparts of larger ORFs in other orthopoxviruses (OPVs). The VACV-List genome also contains several ORFs that have not been annotated in other VACVs but were found in other OPVs. VACV-List and VACV-LO displayed a high level of nucleotide sequence similarity. Compared to the Copenhagen strain of VACV, the VACV-List sequence diverged in three main regions, one of them corresponding to a substitution in VACV-List with coxpox virus GRI-90 strain ORFs, suggestive of prior genetic exchanges. These studies highlight the heterogeneity between VACV strains and provide a basis to better understand differences in safety and efficacy of smallpox vaccines.

Evolution of and Evolutionary Relationships between Extant Vaccinia Virus Strains

“…For example, Lister strains have the fewest genes immediately adjacent to the right TIR boundary, which is located at 71% of DVX_211 (Table 3). Lister is a complex virus and harbors two genes, List195 (18) and List196 (50), that are otherwise found only in VACV USSR and Evans strains (18). However, GLV-1h68, a recombinant clone isolated from an old Lister stock called LIVP, lacks List195 and List196 (49), suggesting that this stock may still contain a mixture of viruses.…”

Extent of Systemic Spread Determines CD8+ T Cell Immunodominance for Laboratory Strains, Smallpox Vaccines, and Zoonotic Isolates of Vaccinia Virus

“…To test how virus strain affected CD8 + T cell responses, we tested a wide range of VACV strains including: Western Reserve (WR), the most common laboratory strain; ACAM2000, the current US smallpox vaccine which is a clone derived from Dryvax® (23, 32, 33); Lister, the most widely used smallpox vaccine; Copenhagen and Tian Tan which were used in Europe and China (34); finally Modified Vaccinia Ankara (MVA), a replication-deficient VACV strain used as a vaccine vector in many clinical trials (35–39). For each virus, mice were infected with 1×10 6 PFU by i.p.…”

Influence of glycosylation and oligomerization of vaccinia virus complement control protein on level and pattern of functional activity and immunogenicity

“…Generally, these strains of vaccinia virus induced severe adverse effects, though mainly in individuals whose immune system was compromised (Henderson et al, 1999;Ober et al, 2002;Empig et al, 2006;Wittek, 2006). The Lister strain of vaccinia virus elicits a strong immune response (take rate of 94%), and was extensively used for immunization in countries such as the UK, Germany, France and South Africa (Rosenthal et al, 2001;Ober et al, 2002;Garcel et al, 2007). Garcel et al (2009) showed that the traditional Lister smallpox vaccine displayed phenotypic and genotypic diversity.…”