By Catherine Tomlinson for Spotlight
HIV is known for its ability to outsmart our immune system’s normal defences. A small number of people living with the virus are however able to generate unusually effective immune responses. In this special briefing, Spotlight zooms in on broadly neutralising antibodies, the secret sauce in these immune responses, and their potential role in the future of HIV treatment and prevention.
Our immune systems are highly effective at identifying and fighting off foreign invaders, such as viruses. One way our immune systems does this is by producing antibodies. In short, antibodies recognise viruses and then latch on to them. This blocks the viruses from entering our cells and flags them for destruction by other parts of the immune system.
One of the most remarkable things about our immune system is that it is able to create an enormous variety of such antibodies tailored to each different virus and other disease-causing pathogen that we encounter over our lifetime.
The human immunodeficiency virus (HIV), however, outsmarts our bodies’ normal immune responses by constantly changing the parts of its surface that antibodies recognise. This makes HIV difficult for antibodies to attach to and neutralise.
After several years of living with HIV, some people are able to produce a special type of antibody, known as broadly neutralising antibodies, or bNAbs. These antibodies are more effective at neutralising HIV than regular antibodies because they recognise parts of the virus that change very little, known as ‘conserved regions’. By targeting parts of the virus that are less prone to change, bNAbs are more effective than regular antibodies in identifying and neutralising the constantly changing virus.
“About 20 percent of people living with HIV naturally develop bNAbs, after many years,” explains AVAC, a US-based NGO seeking to advance the development of HIV prevention tools. “By the time bNAbs have developed in these individuals, the constantly mutating HIV has outpaced these defenders, changing too fast and too significantly for bNAbs to be effective in that individual. But that same bNAb, or a combination of them, may work in someone else,” they say.
A vibrant area of research
Researchers first identified bNAbs in a person living with HIV in the 1990s. Since then, they have discovered many more bNAbs and papers and presentations on the topic have become a staple at HIV conferences. At the 2026 International AIDS Conference held in Rio de Janeiro, Brazil, in July, there were 21 abstracts related to the topic.
Since the 1990s, researchers have learned how to replicate and produce bNAbs in the lab. They have conducted early-stage trials showing that bNAbs can be safely administered to people and they have learned how to engineer bNAbs to increase their potency and make them last longer in our bodies.
Currently, researchers are studying whether bNAbs, given by infusion or injection, can prevent HIV infection in people who are HIV negative and control the virus in people who are already living with it. There is also an interesting cross-over with vaccine research, whereby researchers are trying to develop HIV vaccines that prompt the body into making bNAbs.
Before we dig into the details, it is worth stressing that all of this research is still at an early stage. Whereas bNAbs show promise, they have neither set the world alight, nor completely failed. For now, antiretroviral medicines remain the only effective form of HIV treatment, as well as being an extremely effective form of HIV prevention. It is not clear whether bNAbs will ever reach the high bar set by antiretrovirals.
bNAbs for HIV prevention
One of the big HIV stories of the last decade or so has been the use of antiretrovirals to prevent HIV infection. Antiretroviral tablets to prevent HIV infection are already widely available in the public sector, and since June this year, government has been rolling out the six-monthly lenacapavir HIV prevention injection to around 10% of clinics. Such pre-exposure prophylaxis, taking something to prevent infection, is commonly referred to as PrEP.
One of the big hopes for bNAbs is that an infusion of the cells could similarly work as a form of HIV PrEP. The thinking is that these ‘smarter’ immune responses will be more effective than our regular immune responses in recognising and neutralising the shape-shifting virus, and thus clearing it before it can get a foothold in the body.
Substantial research has already been done in this area with two landmark studies, the AMP trials, having garnered the most attention. In the two trials, researchers evaluated an infusion of a bNAb called VRC01 to prevent HIV acquisition in men and transgender people who have sex with men, as well as in cis-gender women. The trials were conducted by the HIV Vaccine Trials Network (HVTN) and the HIV Prevention Trials Network (HPTN).
The AMP trials found that VRC01 did not prevent HIV infection. While this was disappointing, the studies did make a breakthrough by showing that bNAbs could neutralise strains of the HIV virus under certain conditions. While HIV could shape-shift enough to get around VRC01 and cause HIV infection, VRC01 was able to neutralise the HIV strains that were vulnerable to this specific bNAb.
This pattern of bNAbs blocking some, but not all strains of HIV, has been seen in several other studies. It provides both reason for hope, since there is clearly some efficacy, but also frustration, since the efficacy is not nearly as good as what is achieved with antiretrovirals.
Learning from the AMP trials, scientists are now studying whether combining different bNAbs that target a broader range of HIV strains, as well as different regions of the virus’ surface, into a single infusion or injection can be used to prevent HIV.
HVTN and HPTN’s planned Combo-AMP trial will evaluate whether providing people with a combination of different bNAbs can prevent HIV, explained Fred Hutchinson Cancer Center’s Holly Janes at the recent AIDS Conference.
Beyond the AMP trials, the Durban-based research group CAPRISA has also led important studies on the use of bNAbs for HIV prevention. They recently announced the results of a trial called CAPRISA 012C that evaluated the use of a combination of two bNAbs to prevent HIV acquisition in young women in Southern Africa.
Disappointingly, the combination bNAb provided in this trial did not prevent HIV infection. However, CAPRISA reported that “a positive finding was that there was a trend towards protection when the viruses were sensitive to both or one of the two bNAbs compared to when the viruses were resistant to both bNAbs.” In other words, HIV infections occurred more frequently with strains of the virus that were resistant to the bNAbs studied than with strains that were sensitive to them.
“The CAPRISA 012C trial is a culmination of 22 years of research – while it has not led to a new HIV prevention product, it provides valuable information to guide further bNAb research,” said CAPRISA, adding that sensitivity to bNAbs in contemporary circulating viruses will need to be factored into planning future trials of bNAbs.
bNAbs for HIV treatment
bNAbs are also being evaluated as potential treatment for HIV. Researchers are trying to understand whether, under what circumstances, and for how long bNAbs can control the virus in people living with HIV, with the goal of developing products that can achieve long-lasting HIV control without antiretroviral treatment.
This is important because the emotional and psychological burden of having to adhere to a life-long daily pill regimen to treat HIV is a known cause of poor treatment adherence. For infants and young children there are also practical challenges to swallowing and keeping down daily treatment.
One of the main ways that researchers are evaluating the potential of bNAbs to treat HIV is through analytical treatment interruption (ATI) studies. In ATI studies, people living with HIV are given bNAb infusions or injections – sometimes in combination with long-acting injectable antiretroviral drugs – and then temporarily taken off their regular antiretroviral treatment under close medical observation.
Researchers then monitor how long HIV remains suppressed in order to learn whether and how well bNAbs can control HIV infection.
The results from ATI studies, including the RIO and FRESH trials, have been tantalizing. bNAb infusions have allowed some study participants to remain off antiretroviral treatment for more than a year without the virus rebounding in their bodies.
Yet, the studies have also raised questions about how and why bNAbs have such mixed efficacy. Researchers are still trying to understand why some people are able to maintain periods of viral control after receiving bNAbs, while others experience rapid viral rebound. The reasons for this appear to extend beyond a person’s sensitivity to the specific bNAbs being used to also include other factors related to the characteristics of one’s HIV infection and immune response.
At the 2026 AIDS Conference, Michel Nussenzweig, senior physician at the Rockefeller University, told delegates that research so far indicates that bNAb therapy is more likely to deliver periods of post-treatment control in individuals with a less diverse HIV reservoir, pre-existing autologous antibodies, and pre-existing stem cell like CD8+ T cells.
Scientists are now considering whether the factors associated with bNAb treatment success can be boosted through other interventions, said Nussenzweig.
Another important area of research is whether bNAbs can be used as a form of treatment for infants and young children living with HIV. An infusion or injectable treatment could be a gamechanger for this group, given the challenges faced by caregivers in getting infants and young children to swallow and keep down daily antiretroviral treatment.
The Tatelo and Tatelo Plus studies conducted in Botswana were set up to evaluate whether young children given bNAbs can maintain viral suppression after stopping antiretrovirals. Results from the Tatelo study reported in 2022 showed that some children (44%) who received a combination of two bNAbs were able to maintain a period of viral control (24 weeks) after stopping HIV treatment. The Tatelo Plus study, now underway, is evaluating whether and for how long a combination of three bNAbs can maintain HIV suppression in young children after antiretrovirals are stopped.
bNAbs for HIV vaccination
While bNAbs have not yet been shown to be a practical and effective form of HIV prevention or treatment, research has demonstrated that, under the right conditions, they can protect against and suppress HIV strains that are susceptible to them.
These findings have generated excitement about using bNAbs as a target for HIV vaccines. Unlike research into bNAbs for PrEP or HIV treatment, in which laboratory made bNAbs are infused or injected directly into our bodies, some HIV vaccine researchers are trying to figure out how to trigger our bodies to produce their own bNAbs.
In other words, vaccine researchers are trying to make our bodies, rather than laboratories, the factories that make bNAbs against HIV.
At this stage, scientists do not expect that a single vaccination will be able to trigger our bodies to produce mature bNAbs capable of combating HIV. Instead, they anticipate that a vaccine protocol that involves a series of vaccines will be needed to coax our immune systems to produce mature bNAbs.
While this branch of research remains at its early stages, many HIV researchers are hopeful that it may one day produce an effective vaccine protocol against HIV.
One study to watch is a Phase 1 safety and dosing trial launched by the International AIDS Vaccine Initiative (IAVI) and partners in South Africa at the end of 2025. “The hypothesis being tested is that highly specialized vaccine immunogens, delivered in a specific sequence, can target certain B cells within the immune system and coach them toward the production of broadly neutralizing antibodies against HIV,” says IAVI, adding “scientists widely believe that a vaccine inducing broadly neutralizing antibodies (bNAbs) could provide broad protection against many strains of HIV.”
Where to from here?
Since the first bNAbs against HIV were discovered in the 1990s, scientists have made important, but incremental, progress towards translating these immune responses into tools that can prevent and treat HIV.
As we’ve seen in this Spotlight special briefing, research into bNAbs for HIV treatment is arguably the furthest along, with bNAbs already demonstrating the ability to control HIV during extended periods of antiretroviral treatment interruption in some people. But why some people respond to this treatment and not others remains uncertain. This is an important area for future research.
In the HIV prevention space, bNAbs have delivered protection against HIV strains susceptible to the specific bNAbs studied, but this protection has not been broad enough to protect against HIV infection by the highly diverse, mutating virus. Hope however remains that combining different bNAbs that target different conserved regions of the HIV virus, as well as currently circulating viruses, could broaden protection enough to prevent HIV infection. Here too, as with attempts to develop vaccines that spark the production of bNAbs, it is imperative that the research continues.
Of course, even if scientists can crack the code and find a way to produce highly effective bNAbs, the road ahead might not be a smooth one. For these products to have an impact in the developing world, where they are most needed, they will have to be cost-effective compared to cheap antiretroviral therapy. They will also have to be easy to administer in often stretched and under-resourced healthcare systems.
While much remains to be done, the scientific leads are certainly there, waiting to be explored.
This special briefing is part of a series by Spotlight – health journalism in the public interest. Sign up to the Spotlight newsletter.
