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The potency of neutralizing antibodies is commonly represented by their binding affinity for their targets. However, binding affinity is based on the dissociation constants at equilibrium, which can’t accurately predict the potency against intracellular parasites (viruses, bacteria and some eukaryotes). These organisms primarily multiply inside the host cells beyond the reach of antibodies, and are only accessible when new offsprings are released from infected cells, which exposes them to antibodies in the bodily fluids. As a result, the time it takes on average for a new offspring to find another target cell (the exposure time) should have a direct impact on the potency of antibodies.

Here are several good examples. HPV is a sluggish virus. Newly released HPV particles have to spend hours in the bodily fluid to undergo complex conformational changes and enzymic activation to become infectious, which gives ample time for antibodies and phagocytes to neutralize and destroy them. As a result, even a very low antibody titer can provide sterilizing protection. Malaria parasites are on the opposite end. It takes only 30 seconds for a newborn parasite to latch onto a RBC and invade it. As a result, antibody concentration needs to be several orders of magnitude higher to stop them. HIV can spread via cell-free particles or close contact between infected and uninfected cells (virological synapses). The amounts of antibodies required to neutralize direct cell-to-cell transfer are also much higher. So is there a more detailed mathematical model to describe the relation between exposure time and neutralizing potency? enter image description here

Citations: Explanations for the high potency of HPV prophylactic vaccines The RH5-CyRPA-Ripr Complex as a Malaria Vaccine Target

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