Challenges of developing a vaccine for HIV/AIDS
AIDS has no vaccine or cure. This anomaly in humanity’s otherwise remarkable track record in tackling major infectious diseases is a result of several factors.
Chief among them is that the replication of the human immunodeficiency virus (HIV), which causes AIDS, is an incredibly error-prone process that results in multiple variants of the virus circulating.
The sheer number of all the different strains circulating in the world is in fact the biggest challenge to an HIV vaccine today.
To put it in perspective, HIV has more variants circulating in a single patient at any given point of time than influenza cumulatively generates in one year in all influenza patients around the world combined. And influenza is the second-best virus in terms of genetic variation.
When the immune system encounters a virus, one of its responses is to produce antibodies highly specific to proteins on the virions’ surface.
Each antibody is unique to a small piece of a given protein, and the immune system can generate antibodies against any given fragment of any protein.
The immune system does this by starting with a pool of specialised cells that produce antibodies, called B-cells.
Each B-cell produces an antibody unique to one protein fragment.
When a B-cell encounters a similar protein fragment on a foreign object — say, a virus or a bacteria — it begins to divide and refine the antibody until it binds perfectly to the target.
These antibodies then bind to their corresponding pieces on the viral surface, rendering them incapable of further infection.
The body then retains some of these specific antibody-producing cells in case of a future infection
What is broadly neutralizing antibodies (bNAbs)
In the early 1990s, scientists noticed that in a small subset of HIV-infected individuals, a new kind of antibody was being produced that could neutralise a large number of circulating viral strains.
These broadly neutralising antibodies (bNAb) worked by targeting areas of the viral proteins that the virus couldn’t afford to change, since doing so would make it lose infectivity.
Scientists have since discovered many bNAbs, and they are classified into different groups based on the region of HIV they target.
Some of these bNAbs can effectively neutralise more than 90% of circulating strains.
But there is a catch: a body usually takes years to make bNAbs, and by then, the virus has already evolved to escape them.
It takes years because the parental B-cell that makes the bNAbs is incredibly rare in the starting pool.
What is Germline targeting?
The challenge, therefore, has been to make the immune system produce these bNAbs in large numbers in response to a vaccine.
The route to doing this, called germline targeting, has three steps.
In the first step, those B-cells that can mature into cells that can produce bNAb are identified and engaged to increase their population and prepare them for the second-step, where a booster dose will guide these cells into generating stronger bNAbs against HIV.
The third and final step is to refine these bNAbs such that they can neutralise a wide range of HIV strains.
Recent advancements in HIV
After years of painstaking failures, researchers have established a possible roadmap for the first two steps of germline targeting for two groups of bNAbs.
Four papers recently published in Science journals outlined two promising nanoparticle-based vaccine candidates: N332-GT5 and eOD-GT8.
The teams, showed that using these novel vaccines, it may be possible to engage B-cells to make two different classes of bNAbs.
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