The development of anti-HIV therapy has coincided with the development and enhancement of SPR technology. This is important because the more we know about how the HIV virus gains entrance to our CD4 T cells and suppresses the immune system, the more investigation is needed in understanding the molecular interactions involved for targeted therapy design and development. SPR has played an essential role in the development and understanding of how different anti-HIV therapies used today bind and interact with the HIV virus, preventing it from either entry into our immune cells or replication once inside our cells.

In order to treat a disease such as an HIV infection it first must be understood. Biosensing using SPR technology has been essential in our understanding of the HIV life cycle in humans. Scientists used SPR to studyi how HIV docks with the CD4 molecules on T cells using their gp120 surface protein. Using SPR binding analysis, they were able to study how reverse-transcriptase (RT) works including how it binds using its helix clamp motif and how it is modulated by nucleocapsid protein (NC). SPR’s ability to analyze low affinity and transcient binding allowed scientists to understand how HIV virions bud off of human T cells through p6 binding to Tsg101. As a result, the proteins which are critical to the virus’ life cycle are now used as targets for potential therapies.

SPR played a pivotal role in the determining antibodies for targets against HIV infection. It was used for antibody characterization studies of the different proteins, both from the host and the viru,s for propagation of the infection and the relatively small sample size facilitated epitope mapping. In addition, label-free analysis and purification to determine kinetics, affinity and thermodynamics efficiently yielded the required data.

In clinical settings, SPR was very useful due to its ability to analyze crude samples - sera and spinal fluid - quickly. SPR was important in helping scientists determine the variability and mutation capabilities of HIV which to this day prevent researchers from developing a viable vaccine against the virus.

Even in the absence of viable vaccine options, researchers and clinicians have been able to create very effective therapies against HIV using SPR technology. SPR is used to screen new compounds quickly and efficiently making it an ideal tool for drug discovery against this deadly virus. Scientists were able to use small molecule inhibition assays focused at blocking HIV gp120 protein from interacting with CD4 as well as the CCR5 co-receptor. IN-DNA and rev-RRE replication targets were studied as targets for small molecules therapies. AR177 (Zintevir) was found to bind better and more efficiently to gp120 not IN as scientists discovered its mechanism of action in stopping HIV propagation.

The techniques and processes developed using SPR for HIV studies, such as serum screening and high quality control surveillance, will be essential for other vaccine developments. Scientists are currently using similar techniques in the development of vaccines for malaria, influenza, hepatitis B and cancer.

SPR has provided scientists with an essential tool to understanding how HIV interacts with our immune system and how to develop targets to block such processes. Every step of the HIV biomedical research journey from HIV discovery to therapy design to patient treatment and surveillance has been studied and analyzed using SPR technology.

As instruments such as the Reichert4SPR deliver improvements in sample throughput, scientists will continue to find more applications for SPR technology. Speeding up sample processing and improving fluidics and uptime will prove invaluable in the ongoing search for new and improved drugs and vaccines against these deadly diseases.HIV research and drug development has played such an important role in SPR technology development that it is considered the gold standard for how SPR technology can be applied to improve patient healthcare.

Sources

http://www.ncbi.nlm.nih.gov/pubmed/12648944

http://www.ncbi.nlm.nih.gov/pubmed/20518719

http://www.ncbi.nlm.nih.gov/pubmed/26968647

http://www.ncbi.nlm.nih.gov/pubmed/24068931

http://www.ncbi.nlm.nih.gov/pubmed/24043627

http://www.ncbi.nlm.nih.gov/pubmed/22493667

http://www.ncbi.nlm.nih.gov/pubmed/26996538