Friday, June 12, 2020

Neutralizing Antibodies: Active Immunization and Passive Immunization Against Covid-19

Generally speaking, a person achieves immunity to disease through the presence of neutralizing antibodies, or proteins produced by the body that can neutralize or even destroy toxins or other disease carriers.  Active immunization is the process of vaccination to prevent an infectious disease by activating the body’s production of antibodies that can fight off invading bacteria or viruses.

The neutralizing antibodies (so-called because they stop the virus from being able to infect cells) can also be obtained from outside the body and can be given the recipients as a therapy for the prevention or treatment of a disease. Passive immunization is the process of administering the antibodies against a particular infectious agent.

An easy example is the antibodies against the rabies. In order to get immunity against rabies virus, we can receive rabies vaccine. Usually 2-3 weeks after the administration of the rabies vaccine (usually several courses), the neutralizing antibodies against rabies will develop in recipient’s body – this is called vaccine-induced active immunity. However, rabies antibodies can also be obtained from the human plasma donated by people in plasma collection centers scattered throughout the United States. The pooled plasma can be fractionated, and rabies antibodies can be obtained – these products are called RIG (Rabies Immune Globulin or hyperimmune globulin against rabies). The RIG can be given to the people to obtain so called ‘passive immunity’. If someone had potential exposure to rabies (for example, bite by wild animals) and had no record of rabies vaccination, the RIG should be immediately given to achieve the passive immunity for short period protection.

The same process of active immunity and passive immunity applies to the Covid-19 situation. Below is a table to compare the active immunity vs. passive immunity in Covid-19 situation:

Active Immunity
Passive Immunity
Relies on neutralizing antibodies against SARS-CoV-2 (the virus causing Covid-19)
active immunity results when exposure to a disease organism triggers the immune system to produce antibodies to SARS-CoV-2
 passive immunity results when receiving a therapy containing neutralizing antibodies against SARS-CoV-2
Neutralizing antibodies are generated by our own immune system
Neutralizing antibodies are manufactured or obtained outside the body and then given to the recipients
Active Immunity can be obtained in two ways:
Natural Immunity: obtaining immunity because of infection with Covid-19 (whether it is symptomatic or asymptomatic)
Vaccine-Induced Immunity: obtaining immunity by receiving the vaccine (vaccination) that won’t make someone sick, but will trigger the body to make neutralizing antibodies), which is known as vaccine-induced immunity
passive immunity is provided when a person is given neutralizing antibodies.
Antibody-containing blood products: convalescent plasma obtained from Covid-19 recovered patients
Hyperimmune products (containing concentrated neutralizing antibodies)
Manufactured antibody products
It will take a while for the body to generate neutralizing antibodies
Off-the-shelf, ready to use
Immunity (once obtained) will be longer
Immunity will be shorter
Companies who are working on vaccines: see previous post “Coronavirus Vaccine Tracker - Developing Vaccines Against Covid-19


Key players in the field (examples only):
Neutralizing antibodies cocktail - Regeneron, Eli Lilly, Sorrento Therapeutics

Clinical trials in ‘healthy’ volunteers
Clinical trials in Covid-19 patients
Clinical trials to demonstrate the effect in prevention (prevent from symptomatic Covid-19)
Clinical trials to demonstrate the effect in treatment (speed up the recovery of the symptomatic Covid-19 patients and decrease the mortality)
The development process is longer
The development process is shorter
Larger sample size for clinical trials required for demonstrating the efficacy in prevention of Covid-19
Smaller sample size for clinical trials required for demonstrating the efficacy in the treatment of Covid-19

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