13.03.2026 Immunology

How monoclonal antibodies are redefining the fight against HIV

Research led by Marina Caskey reveals the potential of monoclonal antibodies capable of neutralizing multiple strains of HIV and keeping the virus under control for long periods

Samuel Fernandes

Portrait of infectious disease physician Marina Caskey, of Rockefeller University, indoors with warm amber lighting. She is wearing a denim jacket and smiling at the camera. A circular metallic sculpture appears in the background.

Even with technological advances in antiretrovirals used to treat HIV, the virus that causes AIDS remains a global public health problem. According to estimates from the World Health Organization (WHO), about 40 million people were living with the virus by the end of 2024, and more than 44 million have already died as a result of the disease.

One of the strategies still being studied to contain the infection involves broadly neutralizing antibodies (bNAbs)—molecules capable of binding to the surface of the virus and preventing its entry into human cells. They are known for their high neutralizing capacity against different viruses and strains, which is especially useful for HIV because of the virus’s high level of diversity.

Previous attempts failed to prevent HIV infections primarily because of the virus’s extensive variability. AIDSVAX, for example, was one such initiative aimed at generating an immune response against HIV. However, clinical trials conducted between the 1990s and 2000s showed that AIDSVAX was unable to provide protection against the virus.

Another similar case was the STEP study, which tested an experimental vaccine developed by the pharmaceutical company Merck in the 2000s. The research was terminated after an analysis of initial data showed the vaccine’s lack of efficacy.

Science Arena spoke with Brazilian infectious disease physician Marina Caskey, who has been studying the topic since 2013. In an article coauthored by Caskey and published in Science in May this year, she and her fellow coauthors report a clinical study that provides evidence for the induction of precursors of bNAbs.

Even without broad protection against HIV, these antibodies represent an advance in the development of mechanisms for controlling the virus. Living in New York, Caskey is a professor at Rockefeller University, where she has conducted several clinical studies on monoclonal antibodies and HIV.

The researcher believes that one of the antibodies currently being trialed could become a medication in the near future. The result could open new avenues for controlling the infection, even without the continuous use of antiretrovirals.

Science Arena: How did your career develop in relation to monoclonal antibodies and HIV?

I’m an infectious disease physician and have been working at Rockefeller University since 2006. I came here as part of a project to develop HIV vaccines. So, my work with HIV goes way back, but my focus on monoclonal antibodies began in 2013. One of the other researchers here at the university, Michel Nussenzweig [an internationally recognized Brazilian immunologist, known for his research on monoclonal antibodies] had not planned to do clinical trials. However, this work led him to use HIV as a model for other topics he was interested in studying. It was then that the laboratory identified some very potent antibodies with broad applicability. Which, for HIV, means that they could neutralize several different strains of the virus. This led to the idea that these antibodies could have clinical potential for the disease. At that moment, I was already here, so I began working in his group. Over the past 10 years, we have already conducted several clinical trials studying these antibodies in different ways and in different groups.

How does this type of research you have been doing differ from previous studies that used monoclonal antibodies against HIV?

We know that antibodies protect against new infections. That’s the principle behind vaccination. So, since the beginning of HIV, there has been the idea of producing vaccines that induce antibodies against the virus or of using antibodies that block HIV. But this didn’t work, because most antibodies in people living with HIV are highly specific in their function. They are obsolete because of the enormous diversity of HIV. They don’t even work for prevention, because the virus in circulation has a lot of diversity from person to person, and they also don’t work for treatment, because there are multiple strains of the pathogen even within a single person living with the virus. That’s why the first generation of antibodies failed.

The difference with this new class of antibodies is that they have a broader activity against various strains of the virus. Initial studies we conducted show that, compared to what had been done before, these antibodies were able to reduce the viral load and keep it suppressed even in the absence of antiretrovirals for a prolonged period.

What can be done with these antibodies in the case of HIV?

The interest in these antibodies has grown significantly for prevention, therapy, and cure. In this case, the idea of a cure is to keep the virus suppressed without antiretrovirals. In the case of prevention, injecting these antibodies is not the same as a vaccine. When an antibody is given, it remains in the body for a period of time and then disappears. The idea behind a vaccine is to teach the immune system to produce the antibodies.

What advance do antibodies represent compared with antiretrovirals?

Antibodies have different functions. One part of the molecule recognizes the virus, and when that happens, the pathogen is cleared. This function is like that of antiretrovirals: it prevents the circulating virus from infecting new cells. But when antibodies encounter the virus, or part of the pathogen that is already inside a cell, they mark it. The antibodies then interact with other cells in the immune system to enhance the specific immune response against the virus. This is something that does not occur with antiretrovirals. Antibodies could also be useful against cellular reservoirs of HIV, since this virus enters the cell’s DNA and hides there. This HIV is latent: it persists inside these cells, but the immune system cannot find it. Antiretrovirals have no effect on these reservoirs of infection. But from time to time, these cells start to produce parts of HIV. When this happens, these parts can appear on the surface of the cells. Antibodies can recognize the virus there and can help the immune system attack the infected cell in order to kill it.

How do you see the future regarding these antibodies and HIV?

I think that one of these monoclonal antibodies will become a drug and will be one of the options for treatment. Regarding a cure, I believe that we will learn how to use antibodies, maybe in combination with other molecules that also influence the immune response, to achieve control, at least temporarily, for a period without treatment.

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