Human immunodeficiency virus (HIV), which can lead to Acquired Immune Deficiency Syndrome (AIDS), is one of a group of debilitating human diseases that directly attacks an individual’s immune system, rendering it useless in fighting off infections. Laboratory animals, such as mice, rats, and guinea pigs, have previously been used to test for HIV vaccines, but over time, scientists realized that the immune systems of these small animals are very different from that of humans. Now, a new animal model is being used for HIV vaccine testing: rhesus monkeys. Specifically, rhesus macaques have immune systems more similar those of humans than mice and rats.
But there’s a catch to using these monkeys: they cannot be infected by the HIV viral strain that infects humans. In order to overcome this dilemma, researchers have found a virus similar to HIV that can naturally infect these monkeys, known as the simian immunodeficiency virus (SIV). To test HIV vaccines, scientists developed a chimeric simian-human immunodeficiency virus (SHIV), which is a genetically engineered virus containing the human HIV envelope, but with viral components from SIV, effectively making a human-like HIV virus that can infect the monkeys for further study. But there was another problem with the SHIV viral strain: the only way that the HIV envelope would allow SHIV to infect the rhesus monkey was if there was artificial binding to the CD4 molecule, a primary receptor for HIV cell entry. In order to overcome this, the scientists found that changing a single amino acid in the HIV envelope, Env375, allows SHIV to infect the rhesus monkey with a thousand-fold better viral entry. This increase then allowwed the researchers to successfully test an HIV vaccine.
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Following the discovery of this amino acid, researchers were quickly able to create a set of “designer SHIVs”, which contained HIV envelopes used to research HIV vaccines. These envelopes evoked broadly neutralizing antibodies that can neutralize multiple HIV strains. This might make you wonder: if broadly neutralizing antibodies are able to render multiple stains of HIV virus ineffective, why are researchers still trying to amplify the vaccine? The answer to this question is simple: the HIV viral strains are highly mutable, allowing the HIV virus to continually infect its host organism. Thus, it makes sense to develop a vaccine that elicits an immune response that lasts longer and is able to target HIV even as it mutates. Rhesus monkeys’ immune similarity to humans will help researchers develop these vaccines. As scientists evaluate the molecular pathways through which the HIV envelope and broadly neutralizing antibodies evolve in humans and rhesus monkeys, more stable vaccines can be developed.
Feature Image Source: Activ-Michoko
