Bacterial Antigen for vaccine

Vaccination evolved and improved significantly these past few centuries. Several vaccine technologies have been developed and improved until their production. On the one hand new generation technologies like trendy mRNA vaccines, or older generation viral vector vaccines do not require toxin production to be efficient. On the other hand, traditional technologies like subunit vaccines or toxoid vaccines do require bacterial antigen purification.

Subunit vaccines enabled great improvement in the safety but showed limited long-term protection. They need to be completed with complementary antigens and efficient adjuvants to be more efficient. 

Conjugate vaccines use polysaccharide antigens in order to induce a better immune response than the classical protein antigen vaccines. Latest reviews also suggest using LPS antigens to increase protection. 

Toxoid vaccines can be based on bacterial endotoxins that have been previously detoxified by modification or chemical treatment. The aim is to create an antibody response to this toxin. In such regards, all vaccine manufacturers stay on equal footing in terms of antigen identification. 

Whatever technology is used; fundamentals remain the same: to find the right antigen and prevent disease outbreaks.
There are plenty of antigens to look at, such as: LipoPolySaccharide, PolySaccharides, CapsularPolySaccharide, LipoTeichoicAcid… to induce a safe immune response and a long-lasting protection effect. But identifying antigens is one thing, producing them is another… In that way, producing purified bacterial antigens with efficient yields and ensuring the right quality control have become one of the biggest challenges to stay in the game for bacterial vaccine manufacturers.

Bacterial screening is the first important step, for selecting the right antigens that will be included in your vaccine. LPS-BIOSCIENCES can analyze the LPS structures from several bacterial strains in order to select the strains showing the epitopes you need for your vaccines. Once the right epitope has been selected, it is also possible to enrich the antigen fraction with the one you are interested in.

Knowing that bacterial culture conditions could influence antigen structure and activity: it is very important that you check the structures of LPS antigens when you switch from R&D small scale fermentation to GMP large scale conditions.
Indeed, changing the culture medium or scaling up biomass production come together with the study of antigen structural properties.

Bacterial antigen purification requirements are crucial for all vaccine developers.
Indeed, having the right antigenic structure, and purity, is needed to induce protection against the right serovar. There are many methods described in the literature, for Lipopolysaccharide extraction, however classical methods like the hot phenol/water extraction do not meet with the requirement of preserving the structure and the diversity of bacterial antigens. Using Phenol / water extraction may harm LPS decorations and modify their structure. 

Phenol has been used for ages to extract LPS or separate endotoxins from polysaccharide antigen but the results are mixed in terms of effectiveness. You need several extraction washes to get rid of endotoxins and sometimes it does not work because of specific LPS structures. 

Using innovative and more gentle eco-friendly solvents, and avoiding hazardous ones such as phenols or chloroform, will also become mandatory to manufacture bacterial antigen molecules in the near future. How big would be the impact to adapt a regulatory-certified production method to new regulations? 

This would not only save a lot on regulatory hurdles and financial stress, but also keep operators on the production lines safe as well as avoid toxic effluents to preserve the environment.

Vaccine research often comes with surprises and irregular results during development. Identifying the source is an important matter when it comes to batch purity control in regards to bacterial antigen molecular structures and heterogeneity. 

Half-life and Storage are the most frequently discussed topic. Studies on the lifespan of the antigen are mostly conducted in order to compare its behavior in the product of interest compared to the raw material itself. Indeed, its behavior can vary, and aggregation phenomena can occur over time. 

Also, during the method development , process changes can influence the structure and therefore the activity of the antigen. The implementation of a quality control for the bacterial antigen during the process and, after finalization of the vaccine product, becomes essential. This involves checking its stability over time while controlling its structure. It is also possible to compare the structural modifications of the bacterial antigen that occur at each stage of the process as well as the impurities involved, in order to see the impact on their activity.