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The MYXV SG33 viral strain: a valuable tool to generate vaccines for ruminants

Scientists in the INRA Joint Research Unit for Pathogen/Host Interactions (UMR IHAP) have studied the effects of the myxoma MYXV SG33 viral strain under in vitro and in vivo conditions in sheep. By observing the in vitro genetic response of ovine cells infected by SG33, the team was able to demonstrate that this strain stimulated the immune system of sheep in a highly specific manner, which means that this virus could be a promising platform for the development of vaccines for ruminants.

Troupeau de moutons en herbage. © GIFFARD Florent

When the Myxoma virus (MYXV) was introduced clandestinely in 1952 into a private estate in the Eure-et-Loir region to control damage caused by rabbits, no-one could have anticipated the devastation that would result from this pathogen throughout France. Spreading rapidly through farmed populations, nearly 40% of these animals were destroyed in 1954. Indeed, MYXV infects and propagates in key cells of the immune system of its host (the European rabbit), including the dendritic cells. These antigen-presenting cells stimulate T lymphocytes to trigger an adaptive immune response following infection or vaccination. Their destruction leads to a dramatic weakening of the defences of an animal, which then dies from numerous opportunistic infections. Pathogenic among animals in the Leporidae family (the European rabbit, rarely the hare), this virus is harmless in other mammals. Numerous immunisation strategies have been developed to control the virus (based on the use of attenuated strains or on a similar virus, the Shope fibroma virus), but with mixed results (problems with efficacy or safety, depending on the case).

The SG33 strain

In 1977, the ENVT developed the attenuated MYXV SG33 viral strain (it's name referring to Saurat and Gilbert and 33°C) – which did not trigger the disease in its host – by means of very numerous culture cycles on chicken and rabbit cells. This strain was subsequently widely used for immunisation in France and Europe.

Since then, SG33 has been the subject of numerous studies, and knowledge of this virus has progressed considerably, demonstrating the undeniable advantages of using this strain as a vaccine vector not only in the rabbit but also in other animal species. Indeed, like all viruses in the Poxviridae family, to which this strain belongs, SG33 can trigger strong humoral and cellular immune responses (antigenic properties) and its large genome can be easily modified to allow insertion of genes coding for antigens from other pathogens (production of recombinant viruses). Thus SG33 was the first strain used to construct a recombinant vaccine for European rabbits (simultaneous immunisation against myxomatosis and viral haemorrhagic disease in rabbits). More recently, its genome was entirely sequenced, which meant it was possible to confirm that the substrate for its attenuation was the loss of numerous genes coding for viral pathogenicity factors.

From the hare to the sheep: the race against bluetongue

At a time when bluetongue was spreading throughout Europe, scientists wanted to determine whether SG33 might be a useful tool to develop a vaccine against this emerging disease on the continent. To achieve this, they studied the interactions between this strain and immune cells from sheep, and notably the consequences of a viral infection affecting dendritic cells.

First of all, the researchers were able to show that this virus could infect circulating mononuclear blood cells and dendritic cells in sheep and that the infection was not productive, while at the same time permitting expression of the genes expressed during the viral cycle. In particular, SG33 targeted a specific subpopulation of cells, Langherans cells in the dermis, which meant that transdermal vaccination could be envisaged.

Secondly, the scientists performed an in vitro analysis of the genetic response of infected cells. They thus studied all the genes activated or inactivated following this infection by demonstrating the messenger RNA transcribed – or the transcriptome – using a DNA chip. They observed that this infection led to a true reprogramming of the cell. During an observation period of 8 hours (RNA extractions at 0h, 3h and 8h), the expression of 390 genes was modified (enhanced in 233 genes, diminished in 157 genes). Comparisons with databanks enabled identification of the principal cell functions affected by these changes in expression. These included, notably, apoptosis (programmed cell death), the type 1 INF (interferon) signalling pathway (which inhibits viral replication) and the synthetic pathways for pro-inflammatory molecules (chemokines) that can stimulate a cellular immune response.

These studies have demonstrated the value of using the SG33 viral strain as a vaccine vector in sheep. Further work was recently carried out using a recombinant SG33 virus expressing capsid antigens specific to the ovine bluetongue virus (serotype 8) and showed that a protective immune response could be induced. These findings are currently being published.

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  • S. Top, E. Foulon, B. Pignolet, M. Deplanche, C. Caubet, C. Tasca, S. Bertagnoli, G. Meyer, G. Foucras.2011. Infection of Nonhost Species Dendritic Cells In Vitro with an Attenuated Myxoma Virus Induces Gene Expression That Predicts Its Efficacy as a Vaccine Vector. J Virol 85(24):12982-94
  • B Pignolet, S. Boullier,J Gelfi, M Bozzetti, P Russo, E Foulon, G Meyer, M. Delverdier, G. Foucras, S Bertagnoli. 2008.Safety and immunogenicity of myxoma virus as a new viral vector for small ruminants. Journal of General Virology 89:1371-9.
  • Camus-Bouclainville C, Gretillat M, Py R, Gelfi J, Guérin JL, Bertagnoli S., 2011. Genome sequence of SG33 strain and recombination between wild-type and vaccine myxoma viruses. Emerging Infectious Diseases, 17(4):633-8.
  • Patent n° FR2925067 « Leporipoxvirus-derived vaccine vector »- INRA ENVT
  • Patent n° FR2736358 « Virus myxomateux recombinant »- INRA ENVT
  • S. Top, G. Foucras, M. Deplanche, G. Rives, J. Calvalido, L. Comtet, S. Bertagnoli, G. Meyer. 2012. Myxomavirus as a vector for immunisation of sheep: protection study against challenge with bluetongue virus. Vaccine 30(9):1609-16.