Complement C3 as Adjuvant : Local C3 Activation

Complement C3 as Adjuvant

Complement C3 as Adjuvant

Shown is the 3D structure of the human complement component 3.

Look deep into nature, and then you will understand everything better. – Albert Einstein

The complement system is part of the innate human immune system. It is believed that the complement system represents an early defense mechanism of the organism against pathogenic invaders, long before the rise of antibody molecules.

The complement system exhibits three possible activation pathways. the “classical”, “alternative” and “lectin”-pathway. In contrast to the adaptive immune system, relying on specific receptor and antibody interactions, the alternative activation pathway of the complement discriminates “self” and “hostile” by surface structures and the lack of inhibitors on foreign particles or cells. For this purpose the complement system consists of an intricate network of diverse proteins acting in self-controlled enzymatic activation cascades.

Activation of complement is leading to the opsonisation of pathogens for the adaptive and celluar immune system, the destruction of cell membranes by destruction of osmotic barriers and the support of systemic reactions by release of signal molecules (anaphylatoxins).

Only recently it was discovered that the innate and adaptive immune system are not existing independly. On the contrary, the signalling pathways of both systems are interconnected and cells of the immune system are actively secreting complement proteins. Since the adaptive system is evolved in evolution after the complement system it is more likely to be modulated by complement than vice versa. Due to this background it is not surprising that the adaptive and cellular immune system is acting on signals from the complement system.

The most important molecule of the complement system is complement component 3 or short C3. The protein C3 is the key switch in the enzymatic cascade of the complement system, connecting all activation pathways. C3 is present in the human serum at comparative high concentration. It is able to spontanously covalently attach to surfaces, hence mark these for “inspection”. If it is partly degraded into the fragments C3d or C3dg, but not released, it will act as an strong natural adjuvant.

Based on the structure of a C3-related protein in the venom of the Indian Cobra, PLS-Design has developed a recombinant molecule which is able to safetly and constantly activate complement C3 to attach onto surfaces. PLS-Design has filed patent protection for the process of using this natural mechanism to enhance immune reactions, e.g. in vaccinations. Since the mechanism of C3 activation is enzymatically only small amounts of the activation molecule are needed.

This technology is used in combination with the local immune modulation principle to minimize side reactions and enhance efficieny by local high concentrations of the natural adjuvants complement C3.

Read more about novel adjuvants click here

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