Therapeutic Antibodies vs. Antibodies from Vaccination

Whether our body produces them ourselves, or we receive them as part of a course of therapeutic treatment, antibodies can protect against infection. At the time of writing this blog, we are in the middle of the SARS-CoV-2 coronavirus pandemic. Research is ongoing globally to find an effective treatment, and promising progress is being made by several groups. Miracle drug notwithstanding, it’s likely that both prevention and cure of this disease will involve antibodies. 

Here we take a deeper look into exactly how antibodies are involved in protecting our bodies from disease in both vaccination and in antibody therapy.

What are Antibodies?

Antibodies are proteins made by the immune system’s B cells in response to an entity (an “immunogen”) that it identifies as not belonging there, such as a bacteria or virus. Antibodies recognize only a specific part (called an “antigen”) of a molecule from the invader, such as a piece of an enzyme from a bacterium, or a segment of the spike protein from a virus’s coat, in a very selective manner. 

Each B cell can theoretically recognize a different antigen, and people have an enormous number of different B cells, each with its own specificity. Once a B cell comes into contact with its antigen it is triggered to make copies of itself, and these copies can make copies, and so on exponentially (called proliferation), with each cell secreting these antibodies.

The antibodies bind to the antigen and block virulence by stopping entry into a cell, calling for help from other parts of the immune system and tagging the intruder for removal from the body.

The strength and course of the immune response depends on a variety of factors. These can include dosage, route and manner in which the immunogen is presented, and even how dissimilar the immunogen is to the body’s own molecules. 

The first time your body encounters a threat, say a new form of a rapidly evolving virus like the flu, it can take approximately 2 weeks before our B cells can mount a response and start proliferating and producing antibodies. Thus, our bodies do not have sufficient concentration of antibodies to neutralize the threat for the interim period of time. In this interim period, the bacteria or virus may itself be proliferating – racing against the immune system’s attempt to contain it.

Antibodies in vaccination

Once the immune system has encountered a threat and logged the information needed to neutralize it, it can generate a rapid antibody response against future invasions from the same antigen. However, in many cases, including the current SARS-CoV-2 coronavirus pandemic, the first infection is enough to cause serious harm. This is where vaccinations are critically important – they give our immune systems a head start.

Vaccination happens when an immunogen, for example a non-infectious derivative of a disease-causing organism, is introduced into the body with the intention of priming the immune system against a future assault. An inactivated virus or a viral protein will not reproduce or cause disease, however the immune system will still see it as a threat and mount a response, generating an army of B cells that will stick around and be able to very quickly produce antibodies against the real thing when and if the need arises.

Vaccines not only protect the individual who has been vaccinated, but if a high enough proportion of people have been vaccinated, “herd immunity” can be achieved. The proportion of immune individuals required for herd immunity is based on the average number of people an infected individual will infect. For SARS-CoV-2, it is estimated that at minimum 43% of the population needs to be immune to achieve herd immunity. Where a population has herd immunity, if one person happens to get sick and is contagious, the pathogen is not likely to find another susceptible host to infect and the disease dies out from the population. Herd immunity is especially important to protect those who cannot receive a vaccine.

Ultimately, once enough people have been vaccinated, the disease will not be able to proliferate, and will be eradicated. In 1980, the WHO announced that smallpox was the first successfully eradicated disease, following a global effort by the organization to provide vaccinations.

Antibodies as a therapeutic

When someone gets infected with a disease like SARS-CoV-2 but manages to recover, they’re likely to have made antibodies against various antigens found on the virus. These antibodies can be captured from the donor’s blood and tested for their recognition of and effectiveness against the virus. Promising candidates can be cloned and used as a basis to produce antibodies on a large scale for use as therapy.

For example, Twist Biopharma is collaborating with Vanderbilt University Medical Center (VUMC) to build a proprietary synthetic antibody discovery library based on sequences derived from a recovered COVID-19 patient, and supplying synthetic genes and antibodies for the development of therapies for COVID-19.

Genetic engineering allows antibodies to be tailored to high antigen specificity, as well as to other attributes such as potency, speed of uptake, and half-life. Worldwide more than a hundred antibody therapies have been approved or are currently under regulatory review, for treatments of indications ranging from cancers to macular degeneration to HIV infection. Twist Bioscience’s Variant Libraries, and Twist Antibody Optimization service that use these libraries, both provide routes to rapid therapeutic development.

Antibody therapy is typically designed to be fast-acting, with the antibodies ready to do their job right away. To maintain efficacy, treatments may need to be repeated periodically. Vaccination, on the other hand, takes a while before its effects can be seen, but those effects include long lasting immunity.

In the case of SARS-CoV-2, pursuing both strategies simultaneously is a great way to hedge our bets. Antibody therapy will help fight off COVID-19, while a vaccine should help prevent a viral infection in the first place.