Research results indicate that repeated vaccinations for the HIV vaccine may cause the antibodies meant to block the virus to attack each other, potentially diminishing the vaccine's effectiveness. This significant finding could have implications for the design of vaccines that require multiple doses, such as those for COVID-19 or influenza.
An international research team, including the U.S. Scripps Research Institute and the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, discovered that multiple vaccinations for the human immunodeficiency virus (HIV) could lead to the immune system functioning in unexpected ways, thereby lowering the vaccine's effectiveness. The findings were published on the 18th in the international journal Science Immunology.
The HIV virus attacks the human immune system, weakening immunity. When HIV infection significantly reduces the body's immune strength, infections or tumors begin to appear, which is referred to as acquired immunodeficiency syndrome (AIDS).
Currently, there is a vaccine for HIV, but a single vaccination is insufficient to induce adequate immune responses. This is because the HIV virus mutates into various forms within the body to evade the immune system's attack. Therefore, repeated vaccinations are necessary to enable the immune system to recognize and respond to the diverse forms of HIV. Additionally, the HIV virus has an outer shell (envelope protein) that makes it difficult for the immune system to attack, but repeated vaccinations help to create powerful antibodies that target the virus's weaknesses and assist the immune system in remembering the virus. The HIV vaccine 'Lenacapavir,' developed by the U.S. pharmaceutical company Gilead Sciences, lowers the risk of infection by approximately 96% when administered twice a year.
The research team conducted experiments on rabbits and red-haired macaques to investigate the effects of repeated vaccinations on immune responses to the HIV vaccine. They observed that the antibodies formed after multiple vaccinations, which were initially created to attack the HIV virus (primary antibodies, anti-HIV antibodies), became targets for other antibodies.
Antibodies that attack anti-HIV antibodies are termed 'anti-immune complex antibodies.' These antibodies do not merely attack the anti-HIV antibodies but complicate the immune response by binding with the antigen-antibody complexes. In particular, they occupy positions that should be targeting the virus, causing the immune system to be insufficiently responsive to the virus.
The research team explained the process by which anti-immune complex antibodies are produced. Initially, antibodies that attack HIV are created through vaccination. When these antibodies completely cover critical areas of the virus, the body misidentifies the anti-HIV antibodies as new threats instead of the virus. Consequently, another type of antibody, the anti-immune complex antibody, forms to attack these antibodies. If the HIV vaccine is administered repeatedly, the generation of anti-immune complex antibodies occurs multiple times, leading to inefficiencies in the immune system and ultimately weakening the ability to block the virus.
The research team noted, 'Since such antibody responses have been confirmed in monkey experiments, similar immune responses may occur in humans receiving multiple doses of the HIV vaccine.' They emphasized that similar problems could arise with other vaccines that also require multiple vaccinations. They added, 'To enhance the effectiveness of vaccines, it is crucial to deepen the understanding of the complexity of immune responses during the vaccine design phase' and 'it is necessary to improve antigen design to prevent repeated vaccinations from making immune responses inefficient or to implement technologies that block unnecessary interactions between antibodies.'
Reference materials
Science Immunology (2025), DOI: https://doi.org/10.1126/sciimmunol.adp5218