We've been hearing more about studies and trials on HIV vaccines recently. The intensification of efforts to prevent this deadly virus is promising not only for the people who are infected with HIV but for everyone else as well.
Most recently, last month, we reported that Moderna had launched the phase I clinical trial of its HIV vaccine in Africa. Other than that, in April, scientists were reported to be working on a permanent cure for HIV using new advances in CRISPR gene-editing technology.
And now, a team of scientists from Tel Aviv University is working on a new and unique treatment for HIV and AIDS, according to a report published by The Jerusalem Post. The aim of the study is to genetically engineer type B white blood cells so that the blood cells would be able to secrete neutralizing antibodies against HIV and allow the infection to be eradicated from the patient's body.
The peer-reviewed study was led by Dr. Adi Barzel and Ph.D. student Alessio Nehmad both of whom are from the Tel Aviv University School of Neurobiology, Biochemistry & Biophysics. The two scientists also worked in collaboration with other researchers from Israel and the United States.
Modifying the B cells
B cells, a type of white blood cell, are responsible for producing antibodies against viruses and bacteria. B cells initially form in bone marrow, and as they mature, they move into the blood and lymphatic system from where they spread to the rest of the body.
The research team made use of CRISPR gene-editing technology in order to genetically modify the B cells to produce the antibody. But first, they had to make sure that the B cells could develop the appropriate antibodies before modifying them outside the body to make a one-time injection. That means genetically modifying them from within the human body.
“Until now, only a few scientists, and we among them, had been able to engineer B cells outside of the body, and in this study, we were the first to do this in the body and to make these cells generate desired antibodies,” said Barzel to The Jerusalem Post.
The process of genetic engineering was carried out employing viral carriers, which are engineered not to cause harm and to solely transfer the necessary gene coded for the antibody into the B cells injected into the patient.
“All model animals who had been administered the treatment responded and had high quantities of the desired antibody in their blood,” explained Barzel, adding that the team “produced the antibody from the blood and made sure it was actually effective in neutralizing the HIV virus in the lab dish.”
When the modified B cells come across the HIV virus within the body, the virus stimulates them and pushes them to divide, leading to the spread of antibodies. What's even better is that if the virus evolves, the B cells will also adapt to resist it, making it the first-ever drug that can evolve inside the patient's body, ensuring that the virus will not be able to overpower it.
The results of the study were published in the journal Nature Biotechnology on June 9.
Transplantation of B cells engineered ex vivo to secrete broadly neutralizing antibodies (bNAbs) has shown efficacy in disease models. However, clinical translation of this approach would require specialized medical centers, technically demanding protocols and major histocompatibility complex compatibility of donor cells and recipients. Here we report in vivo B cell engineering using two adeno-associated viral vectors, with one coding for Staphylococcus aureus Cas9 (saCas9) and the other for 3BNC117, an anti-HIV bNAb. After intravenously injecting the vectors into mice, we observe successful editing of B cells leading to memory retention and bNAb secretion at neutralizing titers of up to 6.8 µg ml−1. We observed minimal clustered regularly interspaced palindromic repeats (CRISPR)–Cas9 off-target cleavage as detected by unbiased CHANGE-sequencing analysis, whereas on-target cleavage in undesired tissues is reduced by expressing saCas9 from a B cell-specific promoter. In vivo B cell engineering to express therapeutic antibodies is a safe, potent and scalable method, which may be applicable not only to infectious diseases but also in the treatment of noncommunicable conditions, such as cancer and autoimmune disease.