Their findings are found in PLOS Pathogens’ July 21, 2022 online factor.
The studies concerned the construction of genetically modified plasmids to involve pieces of genetic curtains in components intended to attack a vulnerability in the spike protein of the sars-CoV-2 virus, a component of the virus for mobile binding and infection. Plasmids are small circular molecules of bacteria’s DNA. which are physically separated from chromosomal DNA and can be reflected independently. Scientists can use them to move genetic curtains from one mobile to another, after which the brought genetic curtains can be reflected on the receiving mobile.
The approach, said leader Maurizio Zanetti, MD, a professor of medicine at uc San Diego School of Medicine and head of the Immunology Laboratory at UC San Diego Moores Cancer Center, raises the option of a more sustainable and widely effective solution, the Covid19 vaccine.
“The main points are complicated, but the basics 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 previous studies and development. The pandemic has added new urgency and resources. These vaccines promised a faster way for people, but not without challenges, such as the need for a bloodless chain at very low temperatures.
The resulting mRNA vaccines have fundamentally altered the course of the pandemic, mitigating in particular the severity of illness, hospitalizations and deaths. But in particular, Zanetti said, they don’t do much to block transmission of the virus. Case rates are expanding and decreasing with the emergence of viral variants.
“The purpose at the beginning is not to prevent the disease,” Zanetti said. “It’s mitigating the consequences, lessening the severity and effects of COVID. Vaccines have logrado. mucho. No want to be hospitalized so often. Death rates are falling. All of this has particularly lessened the pressures on fitness systems and society, which is a smart thing. “
But the ever-changing nature of the SARS-CoV-2 virus has revealed that the vaccine’s efficacy varies, depending on the variant, decreasing. The alpha variant, for example, has been found to be more contagious than the “wild-type” strain. In Wuhan, China. La delta variant was more transmissible than alpha and omicron more than delta. Although vaccines continue to provide very broad coverage against serious diseases, the antibodies they induce are becoming less potent in neutralizing the virus, resulting in increased transmission. . SARS-CoV-2 remains a relentless threat to global public health.
Zanetti said most recent work focuses on “quality rather than quantity,” seeking the induction of antibodies that preferentially block the virus’ binding to its mobile receptor and transmission. This results in a more specific antibody reaction with the vaccine.
“In the early days of COVID vaccine development, it was about generating a broad and physically powerful immune reaction,” Zanetti said. “But it was a scattered approach. The vaccine reaction targeted many epitopes (parts of the virus that the host immune formula recognizes) and resulted in an immune reaction that was largely noisy. Most of the antibodies produced did not have the ability to infect the virus. “
“The new studies focus on some of the particular viral spike related to the virus’ ability to infect that appears to be conserved throughout evolution,” said co-director Aaron F. Carlin, M. D. , Ph. D. , Assistant Professor in the Division of Infectious Diseases and Global Public Health at UC San Diego Health. In other words, the site is not replaced with new variants and represents a persistent vulnerability site and a reliable vaccine target.
How’s work
Zanetti and his colleagues built plasmids containing immunogens, molecules that cause B-mobiles to create antibodies, which were engineered into components to demonstrate a spike protein button that is a component of the receptor binding tendency, or RBM. Specifically, those were amino acid residues that act as keys to unlock the mobile door. The keys and lock change.
B lymphocytes are a component of the immune system. They are prodigious manufacturers of antibodies created to respond to and oppose the expression of antigens or unwanted ingredients in the body, such as viruses. antibody for work.
Zanetti and his colleagues cloned the spike protein amino acids decided into the plasmid DNA so that, when injected into the spleen of the mice, the brought immunogenic molecules cause the production of neutralizing antibodies, particularly tuned to the nob directed into the RBM of the viral protein. advice. The researchers then tested their technique on mice with variants of the original SARS-CoV-2 strain (beta, delta, and omicron) and found that the immune reaction was similar across all variants.
“We were a little lucky in opting for our goal at the tip,” Zanetti said, “although it’s also the result of fun and intuition. I’ve been doing this for 30 years. Previous experiments through others had suggested that this may just be a ‘supersite’. I followed my instincts. “
Zanetti said translating those findings into a vaccine for clinical trials will be “an uphill battle. “A lot has been invested in existing approaches, and this is a huge leap from mouse studies to human clinical trials.
But the promise of a vaccine that is effective and easy to administer is irresistible.
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