DNA Origami Used to Induce Strong Immune Response from B Cells: Study
Fri, September 30, 2022

DNA Origami Used to Induce Strong Immune Response from B Cells: Study


A new study showed a unique technique to identify vaccine design rules, which could trigger a strong immune response against viral infections. Lab tests unveiled its potential in various vaccine models for HIV, SARS-CoV-2, and other viruses.

The unique technique in identifying vaccine design rules for viral infections was revealed by scientists at the Massachusetts Institute of Technology (MIT), a private research university in the US. They used DNA origami or the manipulation of DNA structures to induce an effective immune response. Using virus-like structures in lab tests, the technique could provoke human B cells to respond. As such, the technique might be used in the HIV vaccine and adapted for the COVID-19 vaccine. They published their findings in the journal Nature Nanotechnology.

The Global Success of Vaccines

Vaccines are drugs intended to make a person immune to a specific disease. Diseases that can be averted by vaccines are called vaccine-preventable diseases, which include measles, polio, rubella, and smallpox. Meanwhile, some illnesses like influenza are not prevented by vaccines but hindered so patients can recover quickly. Despite the benefits of vaccines, some people are very concerned about the side effects, especially in children. Since vaccines are drugs as well, side effects may be present. Still, the risk is very low compared to most medications.

Whether or not a person supports vaccines, they cannot deny how these drugs changed the lives of millions throughout history. Multiple diseases have been prevented and millions of lives received protection from different vaccines. According to Our World in Data, an online source of research data, records on specific vaccine-preventable diseases showed a substantial decline in cases and deaths in those illnesses.

For diphtheria, the disease could infect 158 cases per million people per year in the US from 1936 to 1945. When the vaccine for it was discovered, no cases per million per year in the country were reported since 2006. In terms of deaths, from 1936 to 1945, the average death rate was 13.7 per million per year, while since 2004, no deaths per million per year were reported. The vaccine led to a 100% reduction in cases and deaths.

For measles, a highly contagious viral infection among children and adults, the estimated number of cases between 1953 and 1962 was 3,044 cases per million per year in the US. After the vaccine was created, the cases dropped to 0.2 per million per year or a 99.99% reduction. Deaths from measles were 2.5 per million per year from 1953 to 1962. With the vaccine, no deaths were reported in the US, showing a 100% reduction.

Another example is tetanus, a potentially life-threatening bacterial infection. Even with medical advancement, there is no cure for this illness and doctors can only help with toxin management. Thus, the whole battle against tetanus will depend on the overall health of the patient. Before its vaccine discovery, four cases per million per year in the US were reported from 1947 to 1949. About 3.2 deaths per million per year were reported as well in that period. But the vaccine reduced cases to 0.14 per million per year or a 96.6% reduction, and reduced deaths to 0.01 per million per year or a 99.6% reduction.



DNA Origami for Vaccine Design Rules

Creating newer vaccines is difficult as pathogens seem to have tricky mechanisms biomedical researchers cannot overcome. For instance, the distinct mechanisms used by HIV allows it to dodge antiretroviral drugs, leading to no one being cured of the illness after years of therapy. However, scientists at MIT may have a solution that can be applied in vaccine models in due time.

Their solution is DNA origami or utilization of virus-like structures to trigger immune cells to respond to an infection. This may be employed in the creation of the HIV vaccine or even the COVID-19 vaccine, which the world needs right now. Scientists folded DNA into that structure and yielded HIV-like particles. The particles replicated the antigens because of their size and shapes, similar to viruses. That caused a strong immune response in human B cells – white blood cells capable of producing antibodies.

"The rough design rules that are starting to come out of this work should be generically applicable across disease antigens and diseases," said Darrell Irvine, a senior author of the study and associate director of Koch Institute for Integrative Cancer Research at MIT.

DNA origami is one of the most recent techniques from DNA molecule research. For decades, researchers have known that DNA molecules can be programmed, which may be used in numerous biological applications, including drug delivery. Mark Bathe, a senior author of the study as well, developed an algorithm for the technique. This algorithm can design and build arbitrary 3D virus-like shapes automatically. Hence, MIT scientists have a precise way to formulate synthetic DNA structures.

The technique in this study has utilized the knowledge in natural viruses that contain antigens on their surfaces, and in B cells that can recognize those antigens. Novel vaccines containing particles of viruses are being developed to mimic B cells. But there is a problem: B cells can only recognize specific sizes, shape, and spacing between antigens. Any errors among these factors may not alert B cells.

Compared to previous studies, MIT scientists designed icosahedral particles or particles based on polyhedron with 20 faces. In virology, viruses with icosahedral capsid would have 20 triangular faces like adenoviruses and polioviruses. Next, they attached an engineered HIV antigen associated with the gp120 protein to the DNA scaffolds. Those were attached at various distances and densities. Then, they tested it to determine if B cells would respond.

Lab tests showed that their configuration induced immune responses from B cells. But the strongest immune response was detected in one configuration: antigens that were not very close on the scaffold surface, meaning the more spacing there was between two antigens, the more likely it would signal B cells.



Underestimation in the Global Vaccination Coverage

In the Ipsos – Perils of Perception survey in September 2017, posted by Our World in Data, the estimated coverage of vaccination worldwide was 85.8%. Several individuals from different countries were asked how many one-year-old children in the world have been vaccinated. Results showed that most people had no idea that the coverage of immunization already reached at least 80%, despite available publication.

The highest coverage was 67% responded by people in Senegal. It was followed by 65% from the people in Kenya, 57% from Nigeria, 50% in India, 45% in Mexico, 42% in Peru, Turkey, and Indonesia, 41% in Brazil, 40% in Saudi Arabia, 39% in South Africa, 37% in Poland, Hungary, and China, 35% in the US, 34% in Russia and Argentina, 31% in Sweden, Great Britain, Germany, and Italy, 30% in Canada and Australia, 29% in Belgium and Spain, 26% in France and South Korea, and 18% in Japan.

Scientists are now looking into the possible use of their DNA origami in SARS-CoV-2. The antigens used in the study can be swapped with the ones in the novel coronavirus. They are currently testing how B cells in the lab will respond to the mimicked SARS-CoV-2.