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Coming Soon – a vaccine medication targeting AIDS, some cancers and infections

A new study shows that people with AIDS might soon be able to be treated with just a single vaccine dose, which potentially acts as a unique new AIDS/HIV treatment.

The early findings are coming from researchers at the Tel Aviv University (School of Neurobiology, Biochemistry & Biophysics and the Sackler Faculty of Medicine) in collaboration with other international research institutions including Rockefeller University; St Jude Children’s Research Hospital, Memphis; and The Scripps Research Institute, La Jolla. 

The main aim of the study was to map out whether it is possible to use in-vivo B cell engineering to secrete broadly neutralizing antibodies (bNAbs) for injection into the blood of people suffering from AIDS/HIV. Previous research has shown that bNAbs are effective in two ways, both as a treatment derived from their ability to target HIV-infected cells, and as a preventative measure for limiting the spread of HIV infections owing to their inhibition of virus transmission from infected cells across boundaries.

White cells are formed inside the bone marrow and then move into the blood and lymphatic system once they mature, spreading throughout the body. 

Type B white blood cells generate antibodies against bacteria and other viruses as well as the virus responsible for AIDS/HIV.

Until this study, trying to use bNAbs as a clinical therapy was impractical, due to the need to investigate the major histocompatibility complex compatibility of donor cells and recipients in each treatment. This would demand specialized medical centers, technically demanding protocols and significant resource dedication.

The goal of the research team was to genetically engineer type B white blood cells that would be able to secrete neutralizing antibodies against the HIV virus responsible for AIDS without having to be fully histocompatible. 

Findings of the Tel Aviv University study

The paper reports on in-vivo B cell engineering using two adeno-associated viral vectors, one coding for 3BNC117 (an anti-HIV bNAb) and the other for Staphylococcus aureus (Cas9). 

They observed minimal clustered regularly interspaced palindromic repeats (CRISPR) which is a family of DNA sequences found in the genomes of bacteria. CRISPR-Cas9 sequences are derived from DNA fragments of Staphylococcus aureus that had previously infected a cell, and is used as a genome-editing tool to edit or introduce genetic mutation at a selected site in the cell’s DNA.

Conclusions

In the new research, the aim is to generate the desired antibodies and then inject the B cells into the body so as to confer resistance to HIV infection. Until now, few scientists have been able to engineer B cells outside of the body. However, in the reported study, they were able to inject the cells and to make these cells generate desired antibodies.

The genetic engineering was done with viral carriers taken from neutralized and non-infectious viruses that were modified only to carry the necessary gene coded for the antibody into the B cells inserted into the patient.

Based on the outcome of this work, the scientists expect that over the coming years they may also be able to produce white cells that can vector other infectious diseases and the types of cancer that are caused by viruses, such as cervical cancer, head and neck cancer and others.

The conclusion of the researchers was that “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.”

FAQ

A short history of HIV/AIDS

HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) has been a leading cause of morbidity since it was first reported in 1981. HIV was transferred from chimpanzees in west-central Africa to humans in the process known as zoonosis. The infection is spread primarily by unprotected sex, but also through contaminated blood transfusions, shared hypodermic needles and also from mother to child during pregnancy.

For the first years, there was no effective treatment and no cure for HIV, but the introduction of Highly Active Antiretroviral Therapy (HAART) has controlled the disease to a large extent. Still, an effective cure has not been found yet. 

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and associated Cas9 treatment are aimed at producing a cure rather than control of HIV. CRISPR-Cas9 is a tool that enables targeted DNA cutting and splicing. It uses a guide RNA that is complementary to CCR-5, a gene present in type B white blood cells. The two nucleic acids bind together and are recognized by the Cas9 nuclease which can then cut the complex at the target site and inactivate it.

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