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Externalized Human Immune System

Rapid Development of COVID Prophylaxis & Treatment Antibodies

Photo of Todd Huffman
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Externalized Human Immune System

Rapid Development of COVID Prophylaxis & Treatment Antibodies

Melanie@PrellisBio.com or Todd@PrellisBio.com

PROPOSAL

Rapidly produce a variety of fully human antibodies to COVID-19 for the purpose of 

conferring temporary immunity and prophylactic treatment options using Prellis synthetic lymph nodes, effectively externalizing a human’s immune system development.

WHY

Antibodies confer protection for up to 3 months after injection, which can be used to protect high-risk / high-value healthcare workers. Antibody therapy can be used for treatment of patients who are already infected to reduce disease severity. 

HOW

Synthetic lymph nodes leverage real human immune responses to rapidly (22 days) produce novel human antibodies for production. The process does not require human infection or massive screening libraries. The surrogate human immune system preselects and produces antibodies that can be immediately tested for therapeutic efficacy and scaled for Phase I/II clinical trial use leveraging existing antibody production technologies. 

ADVANTAGES

  • Direct from dish to scale-up

  • Protective for those who are immunocompromised. 

  • Human antibodies have extremely low side-effects or off-target issues 

  • No human infection is required. 

  • No extensive screening processes are required

  • Antibody evolution is not required

  • Animal testing or use is not required

  • ‘Humanization’ of antibodies is not required

  • Multiple donors may be parallelized to leverage the genetic diversity of human immune systems. 

  • Will work with every human immune system


CURRENT PROCESSES

The current approach to disease is for each person to fight it and develop their own immune system, vaccines are simply an easier version of the disease to fight.  The end result of the fight is an antibody -- but when the disease evolves those antibodies lose potency and the fight begins anew.


Antibodies can be created directly and injected into a human, this is well known.  Standard antibody production processes use an animal host for antibody production. This is followed by a ‘humanization’ process wherein the protein backbone of the animal antibody is exchanged for a human antibody. In animal production there is a loss in specificity and binding strength of the antibody, which nullifies the power of the prophylactic or treatment. The process typically takes years to develop a fully functional human antibody. The global antibody market is $84 Billion a year, and has still only begun to make a dent in disease.


More recently developed approaches use blood from infected patients or in silico development, each of which has significant drawbacks, from needing an infected patient population to large scale testing that may still result in failure. 


Viral drift, or mutagenesis, keeps humanity from moving past infectious disease. Infecting humans cannot be our sustained approach to developing immunity, our population has become too large -- too connected. 


Due to the poor ability of the human immune system to produce long-lived antibodies to corona virus, it is anticipated that vaccines will have low efficacy and this virus will become endemic to our population. Continued mutations and antigenic drift that nullifies antibody treatment must be monitored and responded too extremely rapidly. 

TECHNICAL APPROACH

A better approach is to create human immune systems in synthetic platforms, which allows disease battles to be fought *outside* the healthy human body.  Prellis Biologics creates synthetic human lymph nodes, the battleground of disease, which can be run cheaply and in large quantities, removing the patient’s body from the equation until an immune response is generated.  The resulting immunity is *directly* injected into the patient.  As the disease evolves across the globe the viruses can be pooled and updated immunity can be provided to patients over time to stay ahead of the virus.


Prellis Biologics’ technology creates human antibodies without using animals, instead synthetic organs are created which emulate the human biological processes.  The approach is more dependable and will scale to large numbers and varieties of antibodies, without exposing humans to the disease.  


The process is as follows:


  1. Prellis prints synthetic human lymph nodes and populares them with healthy human blood.  Hundreds of mini-lymph nodes can be created to examine immune responses from donors with distinct genetic backgrounds, or mutants of the virus

  2. The lymph nodes is ‘vaccinated’ -- when presented with the antigen or virus the synthetic lymph nodes recreates the same evolution process as a the human body 

  3. The cells producing the antibody divide and are in excess relative to non-responding cells and can thus be easily selected for with cell sorting methods or dilution based isolation

  4. The antibody sequence can be produced in therapeutic quantities in concert with outside biotechnology or pharmaceutical companies.

  5. Our process does not require human exposure to a disease, can be scaled up rapidly once the antibody sequence is in hand, is fully human and thus ready for therapeutic use, and does not require blood or plasma from infected individuals. 

Prior Results

Prellis has already demonstrated this process against the Zika virus, see Figure 1. where it took only 4 weeks to get human antibody hits against Zika in a synthetic platform.  Prellis has also demonstrated this technique to generate antibodies for human protein CTLA-4.  Prellis Biologics has an issued US Patent and has filed internationally, U.S. Patent # 10,513,691 granted on December 24, 2019.


Figure 1. ELISA of cell media demonstrating Human antibody hits (11) from a 24 well plate against Zika virus (left). Human surrogate lymph node produced with labeled cells by Prellis Biologics (right). 



PROJECT STATUS AND TIMELINE


  • Antibodies against COVID-19

  • B Cell sequences

  • Materials to support planning and coordination of scale up

  • Needs: Prellis will be looking for support in establishing large-scale pharmaceutical partnerships, support in scale-up, and collaborative discovery

  • For updates on project and funding e mail Melanie@PrellisBio.com

BACKGROUND


Human Antibodies were an $84.5 B market in 2017 with a CAGR of 6.3% and are the highest grossing pharmaceutical product in the market. 


Pandemic Use Case: Injection of a specific human antibody can confer viral or bacterial immunity for months without side effects and re-dosing is possible. This is known as ‘passive immunity’. 


Production of Human Antibodies: requires in vivo biology to run a rapid program of evolution and selection “clonal selection” that within 48-72 hours results in a high affinity antibody that can recognize a unique protein antigen with high specificity. 


Typically: Due to the need for spatial relationships between cells of the immune system and sequential, repeated interactions of specific cell types for this process to be achieved, antibody discovery programs are performed by injecting animals with the virus, bateria, or antigen of interest. 


Problem: Human derived antibodies require human infection and retrieval of B cells and/or human donation of plasma. These are limited sources and antibody identification is often slow.

Animal derived antibodies can not be used in human therapeutic interventions. The human immune system recognizes animal antibodies as foreign. The ‘humanization’ process that replaces the backbone of the animal antibody for a human antibody often reduces effectiveness of the antibody in unpredictable ways leading to years of development. 



For further questions: Melanie@PrellisBio.com, Todd@PrellisBio.com 




Did this resource motivate you to change your behaviors?

  • Yes

Did you share this information with your network?

  • Yes

Where are you getting information around COVID-19?

  • Local Government
  • National Government
  • News: Digital
  • WHO (World Health Organization)

What is your current profession?

Scientist

In what city are you located?

Hayward, CA

In what country are you located?

USA

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Team

Hi Todd Huffman welcome to the challenge! Really exciting reading through your inspiration share for the challenge. Has there been progress with this kind of solution for the current case? I'm curious if you might bounce ideas with Ruth Ann Crystal 's team. They have built a handbook for doctors - Coronavirus Handbook for Doctors - where you might reach out to some practitioners. Will be exciting to see what collaboration comes out.