AIDS vaccine: Phase 1 clinical effects with 97% targeted responses

AIDS vaccine: Phase 1 clinical effects with 97% targeted responses  A new milestone in AIDS vaccine! Phase 1 clinical effect is outstanding, with targeted responses in 97% of vaccination.

AIDS (AIDS), the full name is Acquired Immune Deficiency Syndrome, which is a very harmful infectious disease caused by human immunodeficiency virus (HIV). HIV can attack and destroy the human immune system. Therefore, AIDS patients often suffer from secondary infections or tumors due to insufficient immunity, which also makes the mortality rate of AIDS patients extremely high.

More importantly, as an RNA virus, HIV virus has a high frequency of mutations in its genome. Studies have shown that since HIV was transmitted from non-human primates to humans in the early 20th century, HIV has gradually derived and differentiated into many different subtypes in humans.

In February 2019, an international team composed of the World Health Organization and the United Nations AIDS Programme published in The Lancet the title: Global and regional molecular epidemiology of HIV-1, 1990-2015: a systematic review, global survey, and trend analysis [1].

This review study conducted a systematic investigation and analysis of the global molecular epidemiology of HIV-1 from 1990 to 2015. A total of 2203 data sets and 383519 samples were generated, covering 116 countries around the world. The distribution of epidemic subtypes in different countries, regions and the world will continue to change over time. Details: Global AIDS survey and analysis show that the diversity of HIV viruses is increasing rapidly, and prevention and treatment will face greater difficulties

In fact, the high mutation rate of HIV not only greatly affects the treatment of AIDS patients, but also greatly hinders the development of HIV vaccines.

In February 2020, the scientific community had high hopes for the failure of the clinical trial of the AIDS vaccine candidate HVTN 702 [2]. Details: The largest and most promising HIV vaccine project to date declared “complete failure”

However, even after major failures, the scientific community has never given up on AIDS.

On February 3, 2021, the International AIDS Vaccine Initiative (IAVI) and the Scripps Institute announced that the first phase of clinical trials of a new type of AIDS vaccine has produced promising results [3].

Clinical trials have shown that this vaccine successfully stimulated the production of rare immune cells, which are required to start producing antibodies and fighting rapidly mutating viruses. Among the vaccinated participants, 97% of them found a targeted immune response.

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Dr. William Schief, an immunologist at the Scripps Institute and the developer of the new HIV vaccine, presented the results at the International AIDS Society HIV Prevention Research (HIVR4P) online conference, and said: “This research proves the concept of a new HIV vaccine. This concept can also be applied to other pathogens.”

Today, more than 38 million people worldwide are infected with the HIV virus, and it is considered one of the most difficult viruses to deal with with a vaccine-largely because HIV can continue to evolve into different strains to evade the immune system.

For decades, HIV researchers have been seeking to stimulate the immune system to create rare but powerful antibodies-the “Holy Grail” that can neutralize various HIV strains.

These special blood proteins are called “broad-spectrum neutralizing antibodies” (bnAbs). They can attach to the spike protein on the surface of HIV virus particles and make them ineffective by binding to important but difficult-to-access areas. There is little change between the HIV strains.

In this regard, William Schief said: “We hypothesized many years ago that in order to induce broad-spectrum neutralizing antibodies, the process must be initiated by triggering the correct B cells. These cells have special characteristics that make them have the potential to develop into a broad-spectrum secretion. Cells that neutralize antibodies.”

In fact, in this experiment, target cells accounted for only one millionth of the total number of initial B cells! In order to obtain the correct antibody response, William Schief and others first need to activate the correct B cells. The data of this experiment confirms that the vaccine immunogen has this ability. More importantly, the initiation step will be the first step in a multi-step vaccine program designed to elicit many different types of broad-spectrum neutralizing antibodies.

It is worth noting that the strategy of targeting naive B cells with specific properties is again referred to as “germline targeting”-because these young B cells display antibodies encoded by unmutated or “germline” genes.

Professor Dennis Burton, head of the Department of Immunology and Microbiology of the Scripps Institute, believes that this is a great achievement in the entire field of vaccine science. This clinical trial shows that we can drive the immune response in a predictable way, thereby making better new vaccines, not just against HIV. This strategy can also be applied to vaccines against other challenging pathogens, such as influenza, dengue fever, Zika virus, hepatitis C virus and malaria. Thus opening up a new world in vaccinology.

Dr. Julie McElrath, director of the Fred Hutchinson Cancer Research Center, one of the collaborators of this study, said: “This is a landmark study in the field of AIDS vaccines. It proves that it is practical to induce broad-spectrum neutralizing antibodies to fight HIV infection. Feasible. The new design of immunogens, clinical trials and molecular B cell analysis will provide new ideas for accelerating the development of HIV vaccines!”

Reference materials:
1. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30647-9/fulltext
2. https://www.sciencemag.org/news/2020/02/another-hiv-vaccine-strategy-fails-large-scale-study#
3. https://medicalxpress.com/news/2021-02-experimental-hiv-vaccine-primed-immune.html

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