Ectromelia Virus Vaccine

Creative Biolabs is a company specializing in vaccine development. The company has been in the vaccine industry for more than a decade. A large amount of experience, technology precipitation, and reliable services make the company have a high reputation in the industry. We have been engaged in the development and research of poxvirus vaccines for many years, and we are the leader especially in the field of Ectromelia virus vaccine. Our services include the preparation of finished vaccines and specific services in every stage of the vaccine development process.

Ectromelia Virus

Ectromelia virus (ECTV) specifically infects mouse and cause mousepox in diverse species of mice. The virus belongs to genus Orthopoxvirus in family Poxviridae. Disease the virus caused in mice is acute and systemic with a high mortality, which is similar to smallpox in humans. The virus is transmitted from direct contact with infected animals or through their fomites. Viruses that come into the damage on the skin initiate the infection. They replicate there and spread through lymphatics. Viremia usually appears when the virus comes into the blood and subsequently infects liver, spleen or other organs. Once viruses are released from organs, secondary viremia takes place and leads to infection of distal sites of the skin. Symptoms include swelling in the infected sites as a result of inflammatory responses, and perhaps rashes.

Fig.1 Sequence of events during the course of ECTV infection. (Esteban DJ and Buller RM, 2005)

At present, a variety of different types of ECTV have been isolated, and virulence of these viruses vary a lot. Among which, Moscow strain (Mos) is the most virulent. And ECTV strain Naval (Nav) which was separated from an episode in a naval research facility in the US is proved to be lethal in BALB/ c mice. Identity of the two strains of Ectromelia virus is about 99.5% and differences are mainly located in the inverted terminal repeats at the end of the genome and main difference is only within 3 open reading frames. Besides, open reading frames that encode proteins responsible for immunoregulation from different strains are highly conserved.

Virus-Host Relationship

Skin is the primary site for infection with ECTV and includes a huge number of cells that are able to express kinds of cytokines and signaling molecules, the quantity and kind of which are adjusted according to the types of the pathogen. Keratinocytes are the most abundant cells in mouse epidermal cells, accounting for 90% of the total number of epidermal cells, and are key members of the mouse skin immune system. ECTV could encode multiple host-response modifiers (HRMs) to interrupt normal immune response. And these HRMs play their role in blocking receptor-ligand interactions by inhibiting secretions of cytokines or regulating signal pathways. All of which leads to a failure for host to mobilize related inflammatory cells like neutrophils, NK cells, macrophages and subsequent T cells to the infected sites, and also cause a inhibition of apoptosis of infected cells, which further enhance the proliferation and dissemination of the virus.

As for host, there are two mechanisms to combat with the virus including innate immune response and adaptive immune response. And Type I interferons (T1-IFN) and NK cells are the main strategies in innate immunity. Pathogen recognition receptors (PRRs), for example, toll-like receptors, could detect pathogen-associated molecular patterns (PAMPs) in the endosomes or cellular milieu and other sensors like RIG-like receptor, IFI16/ p204, DAI, and cGAS can discern viral nucleic acid in the cytosol as PAMPs. The recognition of PAMPs by PRRs and the signaling factors downstream of PRRs that trigger T1-IFN transcription are essential for the production of T1-IFN. As an important member of the innate immune response, NK cells fight in the first line of anti-viral infection. Studies have show the significant importance of NK cells to control the infection by ECTV. Adaptive immune response plays a vital role in controlling the disease. Antibodies produced by B cells could neutralize virus or activate complement cascade as well as trigger phagocytosis to block the spread of the virus. In addition to humoral immune responses, there is ample evidence that cellular immune responses are vital in controlling mousepox. Mice that deleted CD8 T cells died after ECTV challenge, while deletion of CD4 T cells responsible for virus clearance did not affect mortality. So it is widely accepted that both antibodies and CD8⁺ T cells are required for protecting mice from mousepox.

Fig.2 The cytokine and cellular network in the skin in response to infection. (Esteban DJ and Buller RM, 2005)

The Development of the Ectromelia Virus Vaccine

Vaccinia virus (VACV) has played an essential role in eradicating smallpox and has been widely used for other poxvirus infections evermore. Here, vaccinia virus also has important significance for the prevention of mousepox. Studies suggest that ECTV could replicate in VACV-immunized mice at a comparable level as high as that of non-immunized mice, but the spread of the virus to spleen or liver in immunized mice is greatly limited. These data indicate that vaccinia virus could protect against disease and lethality caused by Ectromelia virus but could not sterilize it. Besides, mice that recovered from mousepox also manifest that homologous immunization is more effective than heterologous immunization but could not eliminate virus either. Some research show that an immediate immunization with VACV or attenuated MVA (modified vaccinia Ankara) soon after exposure to ECTV is protective for mice. Subunit vaccines prepared using the extracellular domain of purified VACV envelope proteins including A27, B5, A33 and L1 simultaneously adjuvanted with combination of CpG and alum could provide complete protection against Ectromelia virus 4-5 weeks after immunization with ABL/CpG/alum (A33, B5, L1 along with CpG and alum) or ABLA/CpG/alum (A33, B5, L1, A27 along with CpG and alum).

With years of research and development experience in mousepox vaccines, Creative Biolabs can provide you with comprehensive services including vaccine design and preparation, preclinical evaluation, immunogenic optimization, mass production, and process optimization. Choosing us will definitely make your efforts in developing mousepox vaccine more efficient.

Reference

1. Esteban DJ. (2005). “Ectromelia virus: the causative agent of mousepox” J Gen Virol.86(Pt 10):2645-59

All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.