A new mouse study by researchers from Tel Aviv University and collaborators demonstrates a potential new treatment for AIDS which may be developed into a vaccine or a one-time treatment for patients with HIV. The study examined the engineering of type B white blood cells in the patient’s body so as to secrete anti-HIV antibodies in response to the virus.
The findings are published in the journal Nature Biotechnology in a paper titled, “In vivo engineered B cells secrete high titers of broadly neutralizing anti-HIV antibodies in mice.” The study was led by Adi Barzel, PhD, senior lecturer and Alessio Nehmad, a PhD student, both from the school of neurobiology, biochemistry, and biophysics at the George S. Wise faculty of life sciences and the Dotan Center for Advanced Therapies in collaboration with the Sourasky Medical Center (Ichilov).
“Transplantation of B cells engineered ex vivo to secrete broadly neutralizing antibodies (bNAbs) has shown efficacy in disease models,” wrote the researchers. “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.”
The technique developed in Barzel’s lab utilizes type B white blood cells that would be genetically engineered inside the patient’s body to secrete neutralizing antibodies against the HIV virus that causes the disease.
Barzel explained: “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. The genetic engineering is done with viral carriers derived from viruses that were engineered so as not to cause damage but only to bring the gene coded for the antibody into the B cells in the body. Additionally, in this case, we have been able to accurately introduce the antibodies into a desired site in the B cell genome. All model animals who had been administered the treatment responded and had high quantities of the desired antibody in their blood. We produced the antibody from the blood and made sure it was actually effective in neutralizing the HIV virus in the lab dish.”
“We incorporated the capability of a CRISPR to direct the introduction of genes into desired sites along with the capabilities of viral carriers to bring desired genes to desired cells,” explained Nehmad. “Thus, we are able to engineer the B cells inside the patient’s body. We use two viral carriers of the AAV family, one carrier codes for the desired antibody and the second carrier codes for the CRISPR system. When the CRISPR cuts in the desired site in the genome of the B cells it directs the introduction of the desired gene: the gene coding for the antibody against the HIV virus, which causes AIDS.”
Based on this study, the researchers expect that over the coming years they will be able to produce in this way a medication for AIDS, other infectious diseases, and certain types of cancer caused by a virus, such as cervical cancer, head and neck cancer, and more.
Currently, the researchers explained, there is no genetic treatment for AIDS, so the research opportunities are vast. “We developed an innovative treatment that may defeat the virus with a one-time injection, with the potential of bringing about tremendous improvement in the patients’ condition. When the engineered B cells encounter the virus, the virus stimulates and encourages them to divide, so we are utilizing the very cause of the disease to combat it. Furthermore, if the virus changes, the B cells will also change accordingly in order to combat it, so we have created the first medication ever that can evolve in the body and defeat viruses in the ‘arms race’.”
