A tiny antibody component has been found effective against SARS-CoV-2. It could neutralize the coronavirus, despite being 10 times smaller than a full-sized antibody.
The tiny antibody component called Ab8 was isolated by scientists at the University of Pittsburgh Medical Center (UPMC), a nonprofit health enterprise. The component was found potent in neutralizing SARS-CoV-2. It was used to construct an experimental drug with potential as a prophylactic and therapeutic drug for COVID-19. Its performance was determined in mice and hamsters in preclinical testing. They published their findings in the journal Cell.
The Top Therapeutic Drug Types in Early 2020
Several therapies are being researched and developed for various diseases, including COVID-19. Due to the nature of SARS-CoV-2, many research groups are developing drugs based on antibodies. The goal of antibody drugs is to neutralize the coronavirus to prevent or treat COVID-19. According to the National Cancer Institute, an arm of the National Institutes of Health, antibody therapy refers to medications that use antibodies to fight infections and tumor cells. Some of the therapies are monoclonal antibody drugs that contain synthetic antibodies, which act similarly to natural antibodies.
Statista, a German portal for statistics, monoclonal antibody drugs are one of the therapeutic avenues explored in early 2020. In a survey in January 2020, immunological anticancer therapies are the widely investigated drugs for cancer with 3,434 research. It is followed by other anticancer therapies with 2,510 research, gene therapy with 1,273, other monoclonal antibody therapies with 1,009, other ophthalmological therapies with 756, anti-infective prophylactic vaccines with 698, neurological therapies with 666, anti-diabetes therapies with 589, immunosuppressants with 544, and anti-inflammatories with 529.
In terms of drug origins, synthetic or chemical origin is the most commonly used source in drug research and development. Chemical origin is involved in 8,921 research as of January 2020. It is followed by biological protein-based antibodies at 2,224, biological protein-based recombinants at 795, biological cellular-based autologous at 602, biological protein-based at 549, biological nucleic acid-based with viral vectors at 485, chemical or synthetic peptides at 478, biological cellular-based at 464, biological with virus particles at 405, and chemical or synthetic nucleic acid at 401.
Typically, antibody drugs are applied to treat different types of cancer. But these drugs can be modified to treat various infections. The antibodies in drugs are designed to block and prevent pathogens from infecting healthy cells. The effect is to delay or stop the progress of infection and enable the immune system to finish the job.
Tiny Antibody Component for SARS-CoV-2
Certain experimental COVID-19 vaccines elicit immune responses to produce antibodies. Eliciting an immune response preps the human body before exposure to the wild SARS-CoV-2. But naturally-produced antibodies are not made equally. Some people have better antibodies than others. This is why experimental vaccines are being tested to determine the optimal dose for preferred antibody activity.
At UPMC, a team of scientists identified a tiny component of antibodies. They isolated it and tested its performance against the novel coronavirus. They found it effective in neutralizing the said virus even though its size is incredibly smaller than a full-sized antibody. This pushed them to develop an experimental drug, which might be used as prevention or treatment for COVID-19. Also, the drug was designed to be compatible with non-injection-based drug delivery modes.
"The COVID-19 pandemic is a global challenge facing humanity, but biomedical science and human ingenuity are likely to overcome it. We hope that the antibodies we have discovered will contribute to that triumph," said Dr. John Mellors, an author of the study and chief of the Division of Infectious Diseases at UPMC.
The tiny antibody component is the variable, heavy chain (VH) domain of one immunoglobulin type in the blood. It has been found in a pool of more than 100 billion potential antibody candidates to bait the coronavirus' spike proteins. Scientists discovered this tiny component amidst convalescent plasma therapy research. While survivors of COVID-19 can donate their plasma for patients, there is a big problem in supply. Moreover, some studies do not find plasma therapy to be an effective COVID-19 treatment. This is because antibodies vary between individuals.
UPMC scientists decided to isolate the gene for one or more antibodies capable of disrupting the coronavirus. An isolated gene could be replicated in the lab and produced massively to treat COVID-19 patients. They sifted through large libraries of antibody components using human blood samples. Several components were identified with therapeutic potential. It included the Ab8 component. Although all components were tested, the Ab8 had the best performance against the live SARS-CoV-2 virus.
Even at low concentrations, Ab8 blocked the coronavirus completely and prevented the pathogen from hijacking cells. This resulted in the testing of different concentration levels of Ab8 against a modified SARS-CoV-2 in mice models. At the lowest dose, Ab8 reduced the amount of infectious coronavirus by 10 times in mice, compared to animals that were untreated. The therapeutic effect was determined as well in hamster models. The potency of the tiny component was observed in advanced electron microscopic techniques.
The experimental drug based on Ab8 is called PittCoVacc. Ab8 is a result when the VH domain fuses to a part of the immunoglobulin tail region. The fusion adds immune functions to the component but minus the bulk of a full-sized antibody. The drug candidate is initially made as a spiky Band-Aid-like patch to remove the need for refrigeration and needles. It is also possible to make an intradermal and intranasal version due to the diminutive size of Ab8. These versions are good alternatives to intravenous administration, which are common in monoclonal antibody drugs.
The experimental drug is being proposed as a vaccine candidate. So far, there are no serious side effects in preclinical testing. This may aid the drug's progress to human clinical trials. The lack of serious side effects may be attributed to the Ab8's inability to bind to human cells. It may mean that the tiny component can only attach itself to viral particles.