Protein-based subunit vaccines, which contain only antigenic proteins from pathogens, are increasingly useful as a vaccine option for the prevention of several infectious diseases, including COVID-19. However, these vaccines often require the recognition of activating receptor receptors on cells that exhibit antigen to stimulate immune responses.
Traditionally, adjuvant is added as a mixture with the protein or bound to the antigen to generate autoimmune vaccines, both of which require complex manufacturing methods.
“The challenge is to make sure our immune cells see both the protein and the stimulant at the same time,” said author Anneliese Ashhurst, PhD, a researcher at the University of Sydney. for this problem, for the first time we have developed a method that synthesizes the protein with a bound reagent as a single molecule. “
A key challenge in making self-administered vaccines is the dissolution of aqueous soluble proteins with adjuvant hydrophobic molecules. The new techniques developed by Australian researchers used synthetic chemistry to decompose hard-grade protein particles with a single-pot native chemical deselenization reaction.
“We found around this problem of holding hydrophobic and hydrophilic molecules together in a vaccine by developing a way to bind the protein and the adjuvant together as one molecule using synthetic chemistry. Our approach overcomes the flexibility problems faced by other methods, “said Richard Payne, PhD, professor of organic chemistry and chemical biology at the University of Sydney.
The rapid approach to self-efficacy vaccine construction will allow researchers to develop a wide range of candidates for preclinical testing, in a time-efficient manner. The team noted that the synthesis of all bacterial proteins by a linked therapist had not previously been performed.
Testing the procedure for wear
“Tuberculosis affects 10 million and kills more than 1.4 million people each year,” Ashhurst said. “Historically, it has been the leading cause of death worldwide from a single infectious agent. To date, the highly effective and safe tuberculosis vaccine has been used in all populations by medical science. stop. “
Currently, the Calmette-Guerin bacmet vaccine, live mycobacterium, is the only vaccine available against tuberculosis. It is effective in infants but has reduced effectiveness in adolescents and adults. Vaccination also poses significant risks to vaccinated individuals, particularly those with HIVAIDS.
As an alternative strategy, the researchers used the new vaccine-building method to generate synthetic self-developed protein vaccines. Mycobacterium tuberculosis. Two vaccine constructs were designed that contained a full-length ESAT6 protein bound to the charge-like receptor 2 (TLR2) – stimulating the recognition of Pam2Cys-SK4 or Pam3Cys-SK4.
The images were presented as vaccines administered intravenously to mice in vivo. This was done to demonstrate the protective effect of violence M. tubers. The researchers found that the vaccines generated CD4 + T interleukin (IL) -17 cells that were specific for the ESAT6 signaling also stimulated substantive immunoglobulin G (IgG) and IgA responses in the blood and lungs . The team studied the immune responses to TLR2 activation in the lungs that triggers the release of IL-1, tumor necrosis factor alpha (TNFα), and IL-6 leading to the recruitment of neutrophils and monocytes and APC activation. , as well as strong T-cell helper Responses 17 (Th17).
In addition, when mice were challenged with a low dose of aerosol M. tubers six weeks after vaccination, mice loads that received the synthetic vaccine had lower loads than mice that were not vaccinated.
“In addition to providing a quick way to develop a range of vaccines for preclinical testing, we anticipate that this lung vaccine method will be particularly beneficial for protection against respiratory diseases,” Warwick explained. Britton, professor emeritus at the University of Sydney. “We hope that the respiratory vaccine for tuberculosis through the use of protein – based vaccines will allow us to develop a universal and safe approach to combating this deadly disease. “
Another key advantage of the synthetic method is that vaccines for a range of diseases can be developed quickly and safely in the laboratory.
“We don’t have to grow the real pathogen in the lab to make the vaccine,” Ashhurst said. “Using this new method, we can quickly and safely make pure vaccines in the laboratory and bring them to animal models for preclinical testing.”
Do you have a particular perspective on your research related to infectious diseases or immunology? Contact the editor today to learn more.
—
Copyright © 2021 scienceboard.net