A new study showed an innovative technique to develop COVID-19 vaccines. The study featured a new bioengineering technique that could elicit greater immune responses against SARS-CoV-2.
The novel bioengineering technique for vaccine development was applied by scientists at Ohio State University (OSU), a US public research university. The technique altered the specific sequences of the messenger RNA of SARS-CoV-2. The altered sequences resulted in more antigens. The boosted antigens yielded better immune responses. The sequences are known as untranslated regions or UTRs. They published their findings in the journal Advanced Materials.
The Messenger RNA in COVID-19 Vaccines
Right now, several COVID-19 vaccines are fast-tracked to expedite review to support quick deployment. Fast track is a designation by the US Food and Drug Administration but a drug maker must apply for it. The main goal of this designation is to combat a major, deadly illness and fulfill an unmet medical need. In this pandemic, the unmet medical need is due to the lack of specific therapy or vaccine for COVID-19. Although the designation is a positive function, it can come with certain risks since the drug will be deployed based on early study findings. As long as the vaccines can significantly reduce the severity of the disease or prevent a large population from getting sick, they may be deployed to effectively control the pandemic.
Some of the vaccines being fast-tracked use the mRNA vaccine design. This design consists of the genetic material of SARS-CoV-2, instead of the virus itself. The messenger RNA of the coronavirus can be attached to a vector, often another virus, to elicit an immune response. The purpose of using mRNA is to eliminate the risk of infection. But the subject may develop adverse events, such as allergic reactions or abnormal body temperature.
The COVID-19 vaccine from Gamaleya Institute uses mRNA attached to either adenovirus type 26 or adenovirus type 5. In the paper published in The Lancet journal, the authors presented the results in Phase 1/2 clinical trials of the vaccine. A total of 76 participants, 38 in each trial, were administered with a rAD26-S or rAd5-S vaccine. The first trial was about the initial shot and its effects observed after 28 days. While the second trial was about the booster and its effects observed after 21 days.
The authors revealed that both adenovirus-based vaccines elicited immune responses in all participants. Even though the vaccine managed to yield a seroconversion rate of 100%, adverse events occurred among participants. The most common adverse event was pain at the injection site reported by 58% of participants. It was followed by hyperthermia at 50%, headache at 42%, asthenia at 28%, and joint and muscle at 24%.
Meanwhile, the Chinese firm Sinovac demonstrated the efficacy of its CoronaVac vaccine in the Phase 2 clinical trial. The results were published in the journal medRxiv. A total of 600 healthy adults aged 18 to 59 years randomly received two injections of one of the two doses or placebo. Participants were assessed in two schedules: day zero and day 14, and day zero and day 28. The lowest dose of the vaccine was found the most optimal. It elicited seroconversion of 92.4% in the first schedule and 97.4% in the second schedule. Similar to the Gamaleya vaccine, pain at the injection site was the most reported adverse event.
Untranslated Regions in SARS-CoV-2 mRNA Sequences
At OSU, scientists applied a new bioengineering method to open avenues for better COVID-19 vaccines. By altering UTRs, the sequences could be made more potent in eliciting immune responses. This could be applied in future COVID-19 vaccines, which would become better than the fast-tracked ones, in theory. The method could be a useful alternative in developing a vaccine at lower doses and reduced side effects.
"If the current vaccines work well, that's wonderful. In case the field needs this, then it's an option. It worked as a vaccine is expected to, and we can scale this up very fast. For now, it's a proof of concept – we've demonstrated we can optimize a sequence of messenger RNA to improve protein production, produce antigens and induce antibodies against those specific antigens," said Yizhou Dong, the senior author of the study and associate professor of pharmaceutics and pharmacology at OSU.
The core of the technique is the same with existing vaccine development methods: utilize the snippets of the pathogen's structure to produce an antigen. The antigen is the foreign substance the immune system recognizes. If introduced in the body, the immune system will react to the antigen. The reaction causes antibody activity and the release of immune cells. This is how an immune response occurs.
In the study, the technique focuses on the mRNA UTRs of SARS-CoV-2. Scientists worked on two UTRs found at the start and end of the protein assembly. These two regulate the assembly and influence the interaction between resulting proteins. Two potential antigens in the coronavirus are known to cause infection in humans. These antigens are the spike protein on the surface and the receptor binding domain. Both can be targeted in vaccine development.
Scientists optimized the cellular process of the two proteins related to the antigens. The optimization increased the antigen levels. Next, they wrapped both antigens in lipid nanoparticles. After that, they injected their experimental vaccine in mice models. Two weeks later, they administered booster shots in the animals. Then, they assessed the immune responses of the animals a month after the injection.
Results showed that the immune system of mice responded well to the antigens. The antibody activity was higher than the average. Also, the antibodies for the antigens lasted 30 days after the vaccine administration. Scientists concluded that the technique could be applied even after COVID-19. As long as mRNA could be utilized in vaccine development, the technique could help develop vaccines for other human-infecting viruses.
Currently, the team is investigating the potential of the bioengineering method in any type of mRNA. They are looking for other therapeutic avenues possible for the technique.