A new COVID-19 vaccine using modified bacterial DNA
Researchers at the University of California San Diego School of Medicine, along with colleagues elsewhere, describe a different way to build a COVID-19 vaccine, which, in theory, would remain effective against new and emerging variants and could be taken in pill form, by inhalation or other delivery methods.
Their findings are published in the July 21, 2022 online issue of PLOS pathogens.
The research involved the construction of plasmids genetically modified to contain pieces of genetic material specifically intended to target a vulnerability in the SARS-CoV-2 virus spike protein, a part of the virus essential for binding and infecting viruses. cells. Plasmids are small, circular DNA molecules from bacteria that are physically separate from chromosomal DNA and can replicate independently. They can be used by scientists to transfer genetic material from one cell to another, after which the introduced genetic material can replicate in the recipient cell.
The approach, said lead author Maurizio Zanetti, MD, professor of medicine at UC San Diego School of Medicine and head of the immunology laboratory at UC San Diego Moores Cancer Center, points to the possibility of a more sustainable and more widely effective solution, Vaccine against covid19.
“The details are complicated, but the fundamentals are simple,” Zanetti said. “They are based on well-known and proven principles and methods.”
COVID-19 mRNA vaccines, such as those from Pfizer and Moderna, are the result of decades of prior research and development. The pandemic has added new urgency, focus and resources. These vaccines promised a faster way for people, but not without significant challenges, such as the need for a very low temperature cold chain.
The resulting mRNA vaccines have fundamentally altered the course of the pandemic, dramatically mitigating the severity of illness, hospitalizations and deaths. But notably, Zanetti said, they’re doing little to block transmission of the virus. Case rates always rise and fall with the emergence of viral variants.
“The goal at the beginning was not to stop the disease,” Zanetti said. “It was to lessen the consequences, to reduce the severity and outcome of COVID. Vaccines did that. Vaccinated people tend not to get as sick. They don’t need to be hospitalized as often Death rates are down. All of this has significantly reduced pressures on health systems and society, which is a good thing.”
But the ever-changing nature of the SARS-CoV-2 virus has revealed that the effectiveness of vaccines varies, depending on the variant, often decreasing. The alpha variant, for example, was found to be more contagious than the “wild-type” strain that originated in Wuhan, China. The delta variant was more transmissible than the alpha and the omicron more than the delta. Although vaccines continue to provide substantial protection against serious diseases, the antibodies they induce are consistently less potent in neutralizing the virus, leading to increased transmission. SARS-CoV-2 continues to be an unrelenting global public health threat.
Zanetti said the most recent work emphasizes “quality rather than quantity,” looking for the induction of antibodies that preferentially block the binding of the virus to its cellular receptor and its transmission. This results in a more targeted antibody response with the vaccine.
“Early on in COVID vaccine development, it was all about generating a broad and robust immune response,” Zanetti said. “But it was a scattershot approach. The vaccine response targeted many epitopes (parts of the virus that the host’s immune system recognizes) and resulted in an immune response that was largely noise. Most antibodies products did not affect the virus’s ability to infect.”
“The new research focuses on a part of the viral spike specifically implicated in the virus’s ability to infect that appears to be evolutionarily conserved,” said co-lead author Aaron F. Carlin, MD, Ph.D. ., assistant professor in the Division of Infectious Diseases and Global Public Health at UC San Diego Health. In other words, the site does not change with new variants and represents a persistent site of vulnerability and a reliable vaccine target.
How it works
Zanetti and his colleagues constructed plasmids containing immunogens — molecules that cause B cells to create antibodies — that were specifically designed to display a spike protein button that is part of the receptor binding motif, or RBM. Specifically, they were amino acid residues that act as keys to unlock the cell’s door. The keys and the lock do not change.
B cells are part of the immune system. They are prodigious antibody producers created to respond to and protect against specific antigens or unwanted substances in the body, such as viruses. The average B cell can spit out 1,000 antibody molecules per second, an incredibly robust output if it’s the right antibody for the job.
Zanetti and colleagues cloned the selected spike protein amino acids into plasmid DNA so that, when injected into the spleen of mice, the introduced immunogenic molecules elicit the production of neutralizing antibodies specifically tuned to the targeted nob on the RBM of the viral protein spike. The researchers then tested their approach on mice with variants of the original SARS-CoV-2 strain (beta, delta, and omicron) and found that the immune response was similar across all variants.
“We had a bit of luck picking our target on the tip,” Zanetti said, “although that’s also the result of experience and intuition. I’ve been doing this for 30 years. Previous experiences by others had suggested it might be a ‘supersite.’ I followed my instincts.”
Zanetti said translating these findings into a vaccine suitable for clinical trials will be “an uphill battle.” There’s a lot invested in current approaches, and it’s a huge leap from mouse studies to human clinical trials.
But the promise of a vaccine that is always effective and easy to administer is irresistible.
“DNA is very stable. New delivery ideas include a pill that survives the digestive system and releases plasmid DNA to be taken up by B cells which appear to have an ancestral property to take up plasmid DNA. Alternatively, DNA can be formulated for delivery into the upper respiratory tract by a formulation suitable for inhalation. Many other researchers and I have already studied and pursued this basic idea in other ways. It is time to try it with COVID.
COVID vaccines: Our current vaccines may soon be updated to target new variants, says immunology expert
PLoS Pathogens (2022). DOI: 10.1371/journal.ppat.1010686
Quote: A new COVID-19 vaccine using modified bacterial DNA (2022, July 21) retrieved on July 21, 2022 from https://medicalxpress.com/news/2022-07-covid-vaccine-bacterial-dna.html
This document is subject to copyright. Except for fair use for purposes of private study or research, no part may be reproduced without written permission. The content is provided for information only.