40 years on the AIDS vaccine is still waiting for the dawn of dawn

Today's perspective

40 years ago, researchers described the mysterious case of 5 gay men who fell ill from Pneumonis carinii pneumonia. Two of the 5 have died.

The U.S. Centers for Disease Control in Atlanta published a report on the strange disease in the June 5, 1981 issue of Morbidity and Mortality Weekly, saying that this type of pneumonia typically affects only individuals who are severely immunocompromised. Scientists soon discovered that a disease that came to be known as AIDS was destroying the immune systems of the men.

Three years later, scientists blamed AIDS on a virus known as the Human Immunodeficiency Virus (HIV). Margaret Heckler, then secretary of health and human services, said at a press conference in April 1984 that the HIV vaccine would be ready for testing within two years and promised protection was coming.

To this day, however, we await the arrival of a vaccine.

At the same time, the AIDS pandemic in Congo, which may have begun in the 1920s, has taken a devastating toll. By the end of 2019, more than 75 million people had been infected worldwide and about 32.7 million had died. If it weren't for advances in anti-HIV treatment, the number of deaths would undoubtedly be higher.

Complex HIV poses challenges for vaccine development

Much of the difficulty in making vaccines comes from the complex biology of the virus itself.

One of the big challenges is the huge genetic diversity that exists between HIV infections among people around the world. Just like the coronavirus, it has variants that are more easily transmitted or able to evade part of the immune system.

However, HIV is particularly complex. Morgan Rowland, a virologist at the Walter Reed Army Research Institute's Military HIV Research Project in Silver Spring, Maryland, said: "This is because HIV replicates its genetic blueprint at a dizzying rate, producing tens of thousands of new copies in one person every day. Each new 'copy' carries at least one unique mutation on average. An AIDS patient can carry countless variants in its body, although only a few can be transmitted to others. ”

What's more, HIV has multiple "strategies" to evade the immune system. For example, it can be covered with a dense layer of sugar molecules on part of its surface. These molecules protect the virus from being attacked by the immune system.

Perhaps the biggest obstacle, however, is the lifelong nature of this viral infection. According to the incomplete news of the Science Times, so far, only 3 people in the world have defeated AIDS. For most patients, it will last a lifetime. Many viruses disappear from the body after the immune system fights them off. However, HIV has the ability to attack the body's immune system, especially to invade T cells, causing T cells to die in large numbers, causing patients to lose all immune function, and various infectious diseases take advantage of the infestation.

Therefore, the "cunning" HIV poses many challenges to vaccine development.

In addition, funding is also an issue. The lack of an effective HIV vaccine stands in stark contrast to the COVID-19 vaccine that took less than a year to develop. Susan Zola-Pazner, an immunologist at mount Sinai Icahn School of Medicine in New York City, said that the funds needed for the development of the new crown vaccine in the United States are constantly flowing, while the funding for AIDS vaccine research is obviously insufficient, so it is difficult to allocate funds to develop vaccines in an effective way. Nonetheless, this flow of funds has spurred progress in HIV research, which has partly made the rapid success of multiple COVID-19 vaccines possible.

The only vaccine closest to success also failed

So far, only a few clinical trials have been used to test the efficacy of a potential HIV vaccine in humans, according to Science Times. Of the six trials completed by the scientists, only one vaccine candidate was shown to be effective in preventing infection.

The only successful trial, known as RV144, used a "prime-boost" strategy, with participants receiving a total of 1 major vaccination and 6 booster vaccinations. Four of the shots contain a canary pox virus that cannot replicate within cells and carries genetic instructions for specific HIV proteins. Participants' cells make these viral proteins and can produce an immune response against them.

The participants then also received two "boosts," one injecting fragments of the HIV protein, which is necessary for the virus to enter the cell. Ultimately, the vaccinated participants had a 31.2 percent lower risk of infection compared to the unvaccinated group.

The results of the RV144 study, first published in the December 2009 issue of the New England Journal of Medicine, showed that specific antibodies were a key factor in reducing the risk of infection. Zola-Pazner said that although the efficacy is limited, it has given scientists an idea of what type of immune response people need to prevent infection, which has helped to promote HIV treatment.

Recently, however, some of the effects of canary pox/protein strategies have been less optimistic. In February 2020, when COVID-19 spread around the world, researchers halted a follow-up trial in South Africa that used the same vaccine platform with the aim of improving the RV144 trial. Researchers reported in the English Journal of Medicine on March 25 that the results of the trial did not reduce the risk of HIV infection in vaccinated people.

Dawn appeared at the dark end of the Tunnel

Now, scientists are working on hive vaccines that provide sterile immunity with a single dose. Of course, any method is also being tried.

One way to do this is to take advantage of the idea that some infected people naturally produce antibodies that are able to attack a wide variety of HIV variant strains and stop these viruses from infecting cells. These antibodies take a long time to form, even years after contracting HIV. Vaccine manufacturers want to speed up the process.

Currently being tested in a clinical trial led by Johnson & Johnson, they used an HIV protein that triggers a widespread immune response consisting of mosaics of different HIV strains that spread around the world.

Another approach is to have the immune system produce a wide range of neutralizing antibodies. The researchers first identified a wide range of neutralizing antibodies in AIDS patients and then analyzed the body's steps in producing these immune proteins. Kevin Sanders, a vaccine expert at the Duke Human Vaccine Institute in the United States, said their goal is to create a vaccine that can produce antibodies similar when exposed to specific pieces of the virus.

In a scientific study in December 2019, researchers such as Sanders showed that in vaccinated mice and rhesus monkeys, they stimulated HIV antibodies so that these antibodies may eventually become widely neutralized. Another study showed that in an early clinical trial, 97 percent of human participants produced equally rare immune cells when exposed to a segment of HIV that specifically produces immune cells.

Other groups focus on T cells to fight infection. For example, Louis Pique and Klaus Fury developed a vaccine that could use specialized T cells to kill other HIV-infected T cells, rather than relying on antibodies to completely prevent infection, the team's results were published in Scientific Immunology in March of this year.

The team's previous research has shown that about half of the monkeys who were vaccinated are protected, and the next step is to transplant the vaccine into humans.

After nearly 40 years of experimentation, there is some light at the end of the "tunnel". "I do believe we're going to develop a vaccine." Zola Pazner said, "But I don't know how long it will take. ”

Peter Piot, founding executive director of UNAIDS and dean of the London School of Hygiene and Tropical Medicine in the United Kingdom, said in an interview with The Lancet on June 5 that he was optimistic about the future of the fight against AIDS.

Piot said the current situation has improved significantly, but HIV mortality rates remain high. The new infections are mainly due to the fact that current measures focus on treatment rather than prevention. Controlling its transmission route is tricky. While there have been results, more efforts need to be made to prevent it. The situation in each country and region is different, and targeted measures should be taken. We are on track to develop an HIV vaccine in the future, but I am also concerned that as COVID-19 continues, many other health and social issues will receive less attention, so changing that will largely depend on strong leadership at the national and global levels.

Source: Science and Technology Daily