There is still a need for HIV treatments and therapies with a preventive capacity that can help increase immune system function with limited unwanted side effects.
From the beginning of the HIV epidemic to date, over 70 million people have been infected, and there have been approximately 35 million mortalities associated with HIV infection. Therapy to prolong life in those infected with HIV include the use of antiretroviral drugs. These drugs effectively lower the HIV body burden to allow recovery of the immune system. There remains a need for therapies with preventive capacity, that can help increase immune system function, and that have limited unwanted side effects.
Antibody therapies, specifically broadly neutralizing antibodies (bNAbs), with potent and broad activity against multiple HIV-1 subtypes and higher safety profiles may be possible candidates to consider as treatments to significantly lower HIV-1 levels. bNAbs have been studied using HIV-1 Env-pseudotyped virus panels, and experiments in animals have shown that these can suppress active HIV-1 infection. This information and results from early-phase clinical trials formed the basis for further studies to determine the utility of bNAbs for prevention and treatment of HIV-1.
Env-pseudotyped viruses produced in 293T cells are used to test the effectiveness of bNAbs. These viruses also represent the main multiple subtypes found in a wide variety of geographic locations. The use of Env-pseudotyped viruses provides a means to test a diversity of proteins with known sequences. However, testing has been done with antibodies with limited potency and effectiveness for the diversity of subtypes, and large differences in sensitivity have been noted between Env-pseudotyped viruses and uncloned viruses produced in peripheral blood mononuclear cells (PBMCs).
A group of scientists performed experiments to compare the sensitivity PBMC-produced HIV-1 isolates with that of Env-pseudotyped viruses to the newer available bNAbs. The researchers found that the current-generation bNAbs also have a much lower neutralization sensitivity against isolates from PBMCs when compared to pseudoviruses. Although this confirms the sensitivity and reproducibility of using Env-pseudotyped viruses for testing assays, the results may inadvertently overestimate the clinical utility or potency of the tested antibodies. Overall, HIV-1 isolates from PBMCs are less sensitive to the newer bNAbs when compared to the pseudoviruses currently used for antibody potency assays. Continued research to better compare in vitro and in vivo antibody sensitivity assay data for extrapolation to the human is paramount.
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