Accelerating Antibody Development During Global Crises

Antibodies as Powerful Therapeutic Tools

In the battle against pathogens such as viruses and their invasion of human cells, our body deploys antibodies to the site of infection. Antibodies are crucial in defending the body against infections by blocking toxins, neutralizing pathogens, and forming adaptive immunity to infection. However, it takes a week for the body to make antibodies used to fight an active infection. 

Nonetheless, highly virulent pathogens can conquer the human host before their B cells can make the antibodies. This dilemma can be circumvented by quickly treating infected patients with therapeutic antibodies, allowing the patient’s immune system to neutralize the pathogenic threat and expedite the recovery process, if not save the patient’s life.

Through advancements in isolating and cloning antibodies, therapeutic antibodies have emerged, revolutionizing treatment for cancer, infections, autoimmune diseases, and more. Antibody-based therapies have been around for more than a century. However, their use in infectious diseases, including viral infections, has long been limited due to high production costs, rapid pathogen mutation rates, and slow antibody production timelines.

Monoclonal Antibodies: The Key Players

Over the years, clinical studies and breakthroughs in isolating potent human monoclonal antibodies (mAb) and understanding antibody structure and functions offered promise for combating a wide range of difficult pathogens.

A surge in research, fueled by the COVID-19 pandemic, was a cornerstone that further accelerated the clinical development of mAb-based therapies with minimal adverse events. Remdesivir was the first molecules to be identified and granted emergency use authorization  amidst the 2020 pandemic by the FDA in the United States.

Today, multiple approaches, including vaccines, various mAb formats, and serum therapy, are being explored simultaneously, reflecting an unprecedented effort to find effective treatments for immune protection. Currently, more than 160 antibody treatments approved by drug regulatory agencies are available, ranging from canonical antibodies and antibody-drug conjugates to bispecific antibodies, antibody fragments, and Fc-fusion proteins.

Active and Passive Immunization for Optimal Infectious Disease Control

Two complementary strategies, active immunization, and passive immunization, are used for effective management of infectious diseases. They ensure comprehensive protection and reduce disease burden and virus transmission, each offering distinct approaches to bolstering the body’s immune response.

Active immunization involves generating immune responses through vaccination. Vaccines play a critical role in disease prevention and control, creating herd immunity. For individuals who cannot fully generate an immune response (such as immunocompromised patients), exogenous antibodies are administered via injection or intravenous infusion. This process, known as passive immunization, provides additional protection.

Active immunization serves as a long-term preventive measure, building immunity within populations and contributing to herd immunity, which reduces the overall transmission of infectious agents. Passive immunization, on the other hand, offers immediate protection from infection to individuals at risk of severe disease or during outbreaks, complementing active immunization efforts.

COVID-19 Pandemic: A Cornerstone

The COVID-19 pandemic, causing serious respiratory tract infections known to cause life-threatening pneumonia, has prompted an extraordinary response from the global scientific community. Researchers and stakeholders have achieved remarkable milestones in record time, including the development of novel vaccines and therapeutic antibodies. These breakthroughs have significantly impacted the course of the pandemic, saving countless lives.

When faced with a novel pathogen, such as the SARS-CoV-2 virus responsible for COVID-19, scientists mobilize to create targeted antibodies. These antibodies can neutralize the virus, prevent its entry into cells, and enhance the immune response. The urgency for COVID-19 treatment accelerated antibody research.

It led to advances in monoclonal antibody (mAbs) development and their use in both the prevention and treatment of SARS-CoV-2 infections as a supplementary strategy for combination therapies. COVID-19 vaccines alone are estimated to have saved many lives within their first year of deployment, while therapeutic antibodies provided additional protection to vulnerable populations.

The scientific community rapidly developed antiviral drugs and therapeutic antibodies to combat COVID-19 infections. Hundreds of antibodies designed to treat COVID-19 patients have been developed, spanning clinical and preclinical studies. These antibodies come in diverse formats, including polyclonal antibodies, monoclonal antibodies, and combinations thereof, forming what are known as cocktail antibodies, and have been crucial in treating the disease.

This shift is expected to have a ripple effect, influencing the approach to addressing other prominent health threats in the foreseeable future.

How Monoclonal Antibodies Can Accelerate Therapeutics

The advancement of human monoclonal antibodies (mAbs) holds great potential in the discovery of novel immunotherapies and treatments for infectious diseases and viral variants. Monoclonal antibodies (mAbs) have emerged as molecules that are quickest to develop during emergencies.

The utilization of mAb strategies has also made a significant mark within emerging infectious disease (EID) outbreaks. Thus, the rapid evolution of mAbs addresses immediate healthcare needs and catalyzes advancements in preventive medicine, heralding a promising era of innovation and accessibility.

Future Pandemic Preparedness

Active and passive immunization offer complementary advantages. Co-development of monoclonal antibodies (mAbs) and vaccines not only presents an opportunity to capitalize on synergies throughout the research and development process, expediting vaccine creation, but also has the potential to give birth to novel products targeting challenging infections prevalent in vulnerable demographics.

Tailored therapies to specific patient groups could also revolutionize the fight against previously insurmountable infections. Research into new technologies remains a cornerstone of future global crises and pandemic-prevention strategies. Investment in novel, adaptable, reliable, and scalable vaccine-development platforms is essential. 

Flexibility is crucial to respond swiftly to emerging variants and evolving pathogens – a need the emergence of SARS-CoV-2 variants-of-concern highlighted. New technologies, such as extending mAb half-life or using mRNA coding for mAbs, may simplify production and administration, eliminating crucial obstacles in the pathogen-specific mAb development process.

Nanobodies, consisting of a single antigen binding domain in a VHH antibody format, are a fascinating class of engineered proteins that offer several advantages over conventional antibodies including their smaller size, stability, and their ability to penetrate tissues. Nanobodies biggest advantage lies in their ability to be developed into medicines that are inhaled into the respiratory tract making them particularly suitable for treating COVID-19.

Staying Ahead of the Curve

In 2021, the NIAID unveiled a pandemic readiness blueprint, drawing on effective approaches honed during the response to SARS-CoV-2 and aiming to fortify defenses against future global health crises, including a prototype pathogen approach for vaccine and monoclonal antibody development. 

This comprehensive plan delineates a research agenda centered on priority pathogens, encompassing known viruses with the potential to endanger public health, such as influenza, SARS-CoV-2, and Ebola viruses, as well as cutting-edge technology platforms and prototype pathogens. 

Artificial Intelligence

Recently, AI technology has had an incredible impact on antibody discovery, optimization, and developability. For example, machine learning (ML) models can predict antibody affinity and non-specific binding using the dataset of antibody libraries for high and low levels of affinity and non-specific binding, enabling the co-optimization of therapeutic antibody affinity and specificity to accelerate the development of highly potent antibody drugs.

Despite being in its nascent phase, the utilization of artificial intelligence (AI) in antibody development has shown notable achievements, particularly in the realm of protein modeling. It signals a clear inclination toward leveraging AI to enhance the feasibility of biotherapeutics, minimize expenses, and broaden accessibility.

From Crisis to Cure: How Global Challenges Propel Therapeutic Innovation

The collaborative efforts of scientists, researchers, and stakeholders have transformed our ability to respond swiftly to infectious diseases during global crises. Nonetheless, the quest for effective antibodies remains a critical part of our journey. By continuing to invest in innovative solutions, we can better prepare for future health challenges. 

The innovation in monoclonal antibody (mAb) engineering and the development of novel formats will be instrumental in forging effective treatments for infectious diseases. At ProteoGenix, we offer comprehensive custom antibody services, from antibody production and development to antibody engineering and characterization.

With over two decades of experience, we’re your one-stop partner who can accelerate your research and contribute to the fight against an array of conditions, including infectious diseases. Book a call to connect with our experts for personalized guidance on your antibody project and take the first step towards achieving your goals.