Four new studies report progress towards long-awaited HIV vaccine

Sub: Science and tech

Sec: Health

Discovery of AIDS:

1981: Michael Gottlieb, an assistant professor at UCLA Medical Centre, aimed to teach immunology to a post-doctoral fellow. He published a paper on these cases in “Morbidity and Mortality Weekly” which was the first report of acquired immunodeficiency syndrome (AIDS).

HIV:

HIV attacks CD4, a type of White Blood Cell (T cells)in the body’s immune system. T cells are those cells that move around the body detecting anomalies and infections in cells.
After entering body, HIV multiplies itself and destroys CD4 cells, thus severely damaging the human immune system. Once this virus enters the body, it can never be removed.
CD4 count of a person infected with HIV reduces significantly. In a healthy body, CD4 count is between 500- 1600, but in an infected body, it can go as low as 200.
Weak immune system makes a person prone to opportunistic infections and cancer. It becomes difficult for a person infected with this virus to recover from even a minor injury or sickness.
By receiving treatment, severe form of HIV can be prevented.

Transmission

HIV is transmitted from person to person through bodily fluids including blood, semen, vaginal secretions, anal fluids and breast milk.
To transmit HIV, bodily fluids must contain enough of the virus. A person with ‘Undetectable HIV’ cannot transfer HIV to another person even after transfer of fluids.
‘Undetectable HIV’ is when the amount of HIV in the body is so low that a blood test cannot detect it. Treatment can make this possible. But regular monitoring of the same through blood tests is also required.

Symptoms

Around 80% of people infected with HIV develop a set of symptoms known as Acute Retroviral Syndrome, around 2-6 weeks after the virus enters into body.
The early symptoms include fever, chills, joint pains, muscle aches, sore throat, sweats particularly at night, enlarged glands, a red rash, tiredness, weakness, unintentional weight loss and thrush.
A person can carry HIV even without experiencing any symptoms for a long time. During this time, the virus continues to develop and causes immune system and organ damage.

Treatment

Anti-Retroviral Therapy:
- It is a combination of daily medications that stop the virus from reproducing.
- The therapy helps in protecting CD4 cells thus keeping the immune system strong enough to fight off the disease.
- It, besides reducing the risk of transmission of HIV, also helps in stopping its progression to AIDS (a spectrum of conditions caused by infection due to HIV).
Stem Cell Transplant:
- Under this, an infected person is treated with stem cell transplant from donors carrying a genetic mutation that prevents expression of an HIV receptor CCR5.
- CCR5 is the most commonly used receptor by HIV-1. People who have mutated copies of CCR5 are resistant to HIV-1 virus strain.

Challenges in HIV Vaccine Development:

Despite significant progress in tackling infectious diseases, AIDS remains without a vaccine or cure.
HIV’s replication process is highly error-prone, leading to numerous variants.
HIV has more variants in a single patient than influenza generates globally in a year.

Immune System Response:

The immune system produces antibodies specific to viral proteins through B-cells.
Each B-cell produces a unique antibody that binds to a specific protein fragment on a virus.
Vaccines aim to generate these antibodies in advance to neutralize the virus upon infection.

Broadly Neutralizing Antibodies (bNAbs):

In the early 1990s, some HIV-infected individuals produced bNAbs that could neutralize many HIV strains.
- Some of these bNAbs can effectively neutralise more than 90% of circulating strains.
bNAbs target critical viral protein regions that the virus cannot change without losing infectivity.
Producing bNAbs takes years, by which time the virus may have evolved.

Germline Targeting Strategy:

Goal: To induce the immune system to produce bNAbs quickly through a vaccine.
Three Steps:

Identify and Engage B-cells: Increase the population of B-cells that can produce bNAbs.
Booster Dose: Guide these cells to generate stronger bNAbs.
Refinement: Enhance bNAbs to neutralize a wide range of HIV strains.

Recent Advances:

Two promising nanoparticle-based vaccines, N332-GT5 and eOD-GT8, have been developed.
Scripps Research Institute and MIT demonstrated efficacy in mice and macaques.
These vaccines are undergoing phase-1 clinical trials in humans.
A protein fragment, g28v2, is being studied as a potential candidate for step II of germline targeting.

Cautious Optimism:

Recent studies show potential in B-cell-based vaccines for HIV.
Past failures remind us to remain cautious until proven effective in humans.
The strategies may also benefit vaccines for other RNA viruses like influenza, coronaviruses, and hepatitis C.

Source: TH