Circumventing HIV-1 immune evasion strategies: utilizing broadly neutralizing antibodies to bolster current drug treatments and develop novel vaccines

Abstract

Human immunodeficiency virus (HIV) attacks the human immune system and if left untreated, causes acquired immunodeficiency syndrome (AIDS). Since its discovery, HIV has quickly become a major public health concern, infecting roughly one million people worldwide each year. HIV employs several immune evasion mechanisms including the targeting of key immune cells, integration of its genome into the host, and infection of uninfected cells through virologic synapses. Advances in antiretroviral therapy (ART) and knowledge of HIV-1 immune evasion strategies have improved our clinical understanding of its pathogenesis and informed new approaches towards developing a vaccine. The primary objective of ART treatment is to lower HIV viral loads and slow the progression to AIDS though the high mutation rate associated with retroviruses facilitates the creation of drug resistant strains. While this presents a challenge to the development of novel drug therapies, there have been several recent breakthroughs using the infusion of broadly neutralizing antibodies (bnAbs) to support ART regimens. Unfortunately, bnAbs are rare and HIV patients have weakened natural immunity to the virus, which complicates vaccine development. Recently, researchers have seen encouraging concentrations of HIV-specific antibodies using a rubella-based live attenuated vaccine in non-human primates though the transition from animal models to human clinical trials has been traditionally cumbersome. Given more recent advancements in our understanding of viral shell disorder, perhaps it is time to consider why the development of an HIV vaccine has been so problematic and to devise new strategies to combat this disease moving forward.