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Why is the development of HIV vaccine so difficult? The scientific secrets behind it are exposed!
HIV vaccine development faces enormous challenges, and even after decades of research, no viable vaccine has yet been successfully introduced. From preventive vaccines to protect healthy people to therapies to treat HIV-infected people, the need for HIV vaccines is becoming increasingly urgent, but the difficulties in developing such vaccines cannot be underestimated.
As early as 1984, then-U.S. Secretary of Health and Human Services Margaret Heckler announced that an HIV vaccine would be available within two years. In fact, researchers have experienced decades of failure and setbacks since HIV was identified as the cause of AIDS. The development of HIV vaccines is different from other classic vaccines mainly due to the following reasons:
“HIV is extremely variable, and even within an infected person the virus evolves rapidly, making it difficult for the immune system’s primary line of defense to effectively recognize and attack the virus.”
HIV has a complex structure and the epitopes of its viral envelope are highly variable, even in the virus of the same infected person. To make matters more difficult for vaccine developers, key epitopes on HIV's gp120 protein are often masked by glycosylation, meaning that even well-designed antibodies may be powerless when faced with these variants.
This high variability and diversity requires that vaccines be designed to cover a variety of variants. Trying to stimulate a robust antibody response also presents challenges, so some researchers have begun focusing on stimulating a response in cytotoxic T lymphocytes.
"There is growing interest in the idea of obtaining broadly neutralizing antibodies (BNAbs), which occur naturally in some HIV-infected individuals and can effectively suppress the virus."
It is noteworthy that VRC01 and other antibodies of this class appear to offer hope for the development of a successful vaccine. These antibodies can effectively prevent HIV from binding to host cells, thereby preventing infection. As research deepens, scientists have a deeper understanding of the types of antibodies and how they are produced, and have launched several clinical trials based on these antibodies.
However, progress in vaccine development does not rely solely on science and technology. The choice of animal model must also be done with caution. For example, commonly used macaque models have SIV (macaque immunodeficiency virus) similar to HIV, but these models are limited in their predictability and direct similarity to human HIV. Recent research from the National Institute of Allergy and Infectious Diseases (NIAID) explored new mouse models that mimic, to some extent, the behavior of HIV.
As clinical trials unfold, many vaccine candidates move from the early Phase I stage to the Phase II stage. Preliminary results are encouraging, with many vaccine candidates performing well in terms of safety and promoting immune responses. However, the effectiveness of these vaccines in preventing HIV infection remains to be further verified.
"In multiple phases of clinical trials, the success rate of vaccines has not been as expected, and some have even shown adverse effects against HIV."
For example, the Phase IIb trial results of the V520 vaccine showed that the risk of HIV infection in vaccinated subjects increased, which forced researchers to re-evaluate the design and strategy of the vaccine. Future studies may focus on vaccine designs that elicit IgG antibodies and show better preventive efficacy.
Taking all factors into consideration, the development of an HIV vaccine is not an easy task. It involves complex virology, immunology and all aspects of clinical trials. In order to solve this scientific problem, readers can't help but wonder, what kind of scientific breakthroughs do we need to make HIV vaccine a reality in the future?
