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 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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Learnerz IAS | Concept oriented UPSC Classes in Malayalam: HIV vaccine UPSC NOTE
Learnerz IAS | Concept oriented UPSC Classes in Malayalam
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