Vaccine Manufacturing as SUMO Fusions

Success of mRNA vaccines has taken the world by a storm. However, many vaccines, especially animal vaccines, have not adopted mRNA approaches. SUMO mediated dramatic enhancement of protein production in E. coli provides a rapid and inexpensive approach to develop protein vaccines, especially for the veterinary markets.

Click to Read More: Understanding SUMO

It is important to understand why the SUMO system has proven to be the best among all other fusion systems (consult LifeSensors’ SUMO Search Engine). The chaperoning properties of SUMO promote correct folding and protect the vaccine from degradation. These factors contribute to dramatically enhance protein production and improve quality of the vaccine. E. coli provides an attractive platform to express animal vaccines for its low cost.  The SUMO system provides facilities to increase protein yield and is a tool to rapidly purify the antigen. LifeSensors can guide scientists about the most suitable SUMO tag and the SUMO protease to efficiently remove SUMO to reduce cost of goods. LifeSensors can guide you from your cloning strategy to selection of strains/cell lines for the best expression and establish a non-GMP process from gene to vaccine. The process can be easily adapted for downstream GMP production of vaccine.

The SUMO Tag

SUMO (Small Ubiquitin-like Modifier) is a member of the ubiquitin family, composed of a flexible N-terminal region followed by a ball-shaped ubiquitin-like fold. SUMO’s hydrophobic core improves correct folding of the fused vaccine, and hydrophilic surface keeps the nanobody soluble. SUMO protease recognizes SUMO structure to cleaves at the junction to generate desired N-terminus of the vaccine.

SUMO protease cleaving vaccine of interest

Figure 2: The Principle of the system. SUMO Protease cleaves the SUMO 6xHis tag to separate the expressed vaccine to generate native vaccine. In many cases SUMO tag is not removed and SUMO-vaccine is as efficacious. SUMO tag does not influence immunogenicity of the fused protein. The 6xHis is used to assist in purification while SUMO significantly improves expression.

the protein structure of SUMO

Figure 1: The unique string and ball structure of SUMO allows for improved expression due to a hydrophilic outer surface and a hydrophobic core.

vaccines expressed using SUMO

Table: Several vaccines have been previously expressed using the SUMO system. SUMO is a powerful expression mechanism to increase yields and improve solubility. References are included at the end of the page.

SUMO is a highly conserved eukaryotic protein. In LifeSensors’ experience SUMO tag is not immunogenic when injected into rabbits. Therefore, it is quite feasible to inject SUMO-fusion vaccine as an immunogen, especially for veterinary applications. This simplifies the manufacturing process and reduces the cost of vaccine production.

LifeSensors has established a curtailed list that allows you to search a variety of papers that describe the application of SUMO to express proteins, polypeptides and nanobodies, see below.

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Click for: Lifesensors' SUMO Publication Searchable Sheet

To use, simply utilize the drop down arrows in order to search for your target of interest or application category. Lifesensors SUMO technology has been utilized for the expression of many different targets, and continues to be utilized worldwide.

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1.Prejit et al, Biologicals. 2019
2.Guo HC et al, Vet Res. 2013
3.Kim WS et al, Vaccines (Basel). 2020
4.Xiao Y et al, BMC Biotechnol. 2016
5.Xiao Y et al, Front Vet Sci. 2021
6.Li H et al,  Vaccines (Basel). 2021
7.Du L et al, Virology. 2009
8.Tarczewska A et al, Int J Biol Macromol. 2021
9.Liu X et al, BMC Vet Res. 2020
10.Mustopa AZ et al, J Genet Eng Biotechnol. 2022
11.Mu S et al, Vaccines (Basel). 2020
12.Cibulski S et al, Front Immunol. 2021
13.Murphy N et al, Sci Rep. 2020