Latest News from the Immunogenicity Studies Front



Pharma IQ
03/14/2011

Immunogenicity is a complex series of responses to a foreign substance, the production of neutralising and non-neutralising antibodies and immune complexes, and different reactions and responses. Scientists have been working on the immunogenicity of proteins to enhance the safety and effectiveness of protein vaccines and drugs. They have met with a lot of success during their trials, which is why the FDA and EMA are starting to warm up to the method.

Using novel in vitro and in vivo assay techniques

Scientists are working hard to create in vitro and in vivo techniques to predict the immunogenicity of a protein. Predicting immunogenicity is important since the possible effects act as a major roadblock in designing many protein-based drugs and vaccines. Novel methods have proven to be very effective in this aspect, especially since they are able to regulate immunogenicity.

Two ways in which novel methods are used are IgG Chimeric Fusion Proteins and Gene Therapy. IgG chimeric fusion proteins and gene therapy have provided additional insights into the world of immunogenicity. Due to them, scientists have started focusing on regulatory T cells in tolerance mechanism models and other models.

Latest comparative immunogenicity studies

In addition to proving useful while creating protein-based drugs, immunogenicity studies have proven quite useful during the early stages of the development of many studies. For example, in 2009, it was proven that older people aged 65 were able to react normally to 60% of the influenza vaccine dose. Anyone receiving the full dose through IM was not able to exhibit improved seroprotection rates whereas those who received the same amount through ID routes showed local reactions of redness, swelling and itching.

Today, one of the most popular comparative studies using immunogenicity is that conducted on the HIV-1 Clade C envelope proteins. The study aims at discovering a reliable and effective HIV vaccine. Previously, clinical efficacy trails couldn’t support the development of recombinant gp120. However, the RV144 HIV vaccine trial in Thailand proved that a prime or boost immunisation strategy can help provide some sort of protection from the HIV virus.

After these results, the development of rgp120 antigens became popular. For an experiment funded by the National Institutes of Health (NIH), a panel of 10 clade C rgp120 envelope proteins was expressed in 293 cells and used to immunize guinea pigs. The sera created were collected and analyzed for binding and blocking activities. Virus neutralisation studies were conducted with the help of two different assays and panels of clade C viruses. Most immunogens were able to neutralise tier 1 clade B viruses and some even managed to neutralize multiple clade C viruses.

Another area where immunogenicity is proving to be beneficial is in comparative studies on in vitro and in vivo immunogenicity of supercoiled and open circular forms of plasmid DNA vaccines. Due to these, supercoiled DNA proved to be three times more effective in priming a MVA-boosted CD8 T cell response. This result helped drug manufacturers shift their concentration away from producing many open circular plasmid DNA vaccines, therefore saving their money, time and resources.

Immunogenicity in nanomedicines

Nanomedicine, the medical application of molecular nanotechnology, is becoming a very popular concept because it offers to do so much as the cellular level. Because nanomedicines need to delve deep into the body, they should be able to make their way without causing immunogenic responses. A lot of research is dedicated to immunogenicity in nanomedicines, especially in the field of immunotherapy and vaccines.

An experiment by a group of Hungarian scientists in November 2010 was able to create an invention that relates to a pharmaceutical composition consisting of nanoparticles made of macromolecules and linear polyethyleneimine (1-PEI) or 1-PEI derivative in a liquid formulation. More experiments and inventions are still underway in the field of nanomedicines, so until those are shared and thoroughly tested, the world of pharmaceuticals need to wait and see.

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