Context: Researchers at the Scripps Research Institute and the Massachusetts Institute of Technology have outlined two nanoparticle-based vaccine candidates: N332-GT5 and eOD-GT8. These novel vaccines could help the body make two classes of broadly neutralising antibodies to attack HIV.
HIV and AIDS:
- HIV (human immunodeficiency virus) is an RNA virus. It belongs to the retrovirus family, which is characterised by the presence of RNA as its genetic material.
- HIV damages the immune system and attacks cells that help the body fight infection, making a person more vulnerable to other infections and diseases. If left untreated, HIV can lead to the disease AIDS (acquired immunodeficiency syndrome).
- HIV primarily targets CD4 cells, which are a type of white blood cell essential for the proper functioning of the immune system.
- Transmission:
- Contact with certain bodily fluids (infected blood, semen, or vaginal fluids) of a person with HIV, most commonly during unprotected sex or sharing injection drug equipment.
- Can also transmit from an HIV-positive mother to her child during childbirth, breastfeeding, or pregnancy.
- Mosquitoes or any other insect vector cannot transmit HIV, unlike malaria (HIV can only survive in human blood).
- Treatment: Human body cannot get rid of HIV and no effective HIV cure exists. Medications like antiretroviral therapy or ART can control the infection and prevent disease progression.
No vaccine for AIDS:
- AIDS still has no vaccine or cure. The reason is that the replication of the human immunodeficiency virus (HIV) is an incredibly error-prone process that results in multiple variants of the virus circulating.
- 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.
Starring role for B-cells:
- When the immune system encounters a virus, one of its responses is to produce antibodies highly specific to proteins on the virions’ surface.
- The immune system does this with the help of a pool of specialised cells (B-cells) that produce antibodies. Each B-cell produces an antibody unique to one protein fragment.
- These antibodies then bind to corresponding proteins 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.
- A vaccine aims to generate these antibodies prior to viral infection so that whenever a virus enters the body, the antibodies can neutralise the virus and prevent it from initiating an infection.
Broadly neutralising antibodies (bNAb):
- However, when multiple variants of the same virus exist, generating antibodies against all the different variants simultaneously becomes very difficult.
- Incase of HIV, the sheer volume of different variants of the virus circulating overwhelms the immune system’s ability to generate new antibodies.
- Additionally, by the time the immune system makes antibodies against a few strains, the virus will have produced hundreds more variants.
- Broadly neutralising antibodies (bNAb) are a kind of antibody that can neutralise a large number of circulating viral strains. These antibodies (bNAb) worked by targeting areas of the viral proteins that the virus could not afford to change, since doing so would make it lose infectivity. Scientists have discovered many bNAbs, and they are classified into different groups based on the region of HIV they target.
The challenge and the way forward:
- 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-cells that make the bNAbs are incredibly rare.
- The immune system can produce these bNAbs in large numbers in response to a vaccine by germline targeting. It 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.
- In the second-step, a booster dose will guide these cells into generating stronger bNAbs against HIV.
- The final step is to refine these bNAbs such that they can neutralise a wide range of HIV strains.
Progress:
- Researchers have developed two promising nanoparticle-based vaccine candidates: N332-GT5 and eOD-GT8. Using these novel vaccines, it may be possible to engage B-cells to make two different classes of bNAbs.
- The antibodies generated in response to the vaccines bind to the HIV proteins in a manner similar to that of established bNAbs. The candidate vaccines are currently being evaluated in a phase-1 clinical trial to assess their performance in humans.