HIV/AIDS drugs could be repurposed to treat AMD, researchers suggest

Drugs that have been used for the past 30 years to treat HIV/AIDS, could be repurposed to treat the dry form of age-related macular degeneration (AMD), a new study suggests. Age-related macular degeneration is a progressive condition that is untreatable in up to 90 percent of patients and is a leading cause of blindness in the elderly worldwide. The two forms of age-related macular degeneration, wet and dry, are classified based on the presence or absence of blood vessels that have invaded the retina.

Age-related macular degeneration is a progressive condition that is untreatable in up to 90 percent of patients and is a leading cause of blindness in the elderly worldwide. The two forms of age-related macular degeneration, wet and dry, are classified based on the presence or absence of blood vessels that have invaded the retina. A detailed understanding of the molecular mechanisms underlying wet age-related macular degeneration has led to several robust FDA-approved therapies. In contrast, there are no approved treatments for dry age-related macular degeneration thus far.

Nucleoside reverse transcriptase inhibitors (NRTIs) are the most widely used class of anti-HIV drugs. NRTIs are thought to be therapeutic in HIV/AIDS patients because they target the enzyme reverse transcriptase, which is critical for replication of HIV. Previous work from the Ambati lab found that a type of toxic molecule called Alu RNA accumulate in the retina to cause dry age-related macular degeneration; interestingly, Alu RNA and HIV are similar in that they both require reverse transcriptase to fulfill their life cycle.

In their Science publication, Fowler et al. report that multiple FDA-approved NRTIs prevented retinal degeneration in a mouse model of dry age-related macular degeneration. Surprisingly, this effect of NRTIs in the eye was not due to the well-known function of these drugs to inhibit reverse transcriptase. Instead, NRTIs blocked an innate immune pathway called the "inflammasome," even in experimental systems in which the NRTIs were not capable of blocking reverse transcriptase. In their report, they also showed that NRTIs were effective in other disease models that share common signaling pathways with the dry age-related macular degeneration model, including the "wet" form of age-related macular degeneration -- a disease that when treated still does not lead to substantial vision improvement in two-thirds of patients -- and graft-versus-host disease which is the major obstacle preventing successful allogeneic hematopoietic stem cell transplantation.

"Repurposing of NRTIs could be advantageous, for one, because they are very inexpensive. Moreover, through decades of clinical experience, we know that some of the drugs we tested are incredibly safe. Since these NRTIs are already FDA-approved, they could be rapidly and inexpensively translated into therapies for a variety of untreatable or poorly treatable conditions," said Benjamin Fowler, the lead author and a postdoctoral fellow in the Ambati lab. Ambati added, "We are excited at the prospect of testing whether NRTIs could be effective in halting the progression of age-related macular degeneration in patients."

NRTIs were originally designed to treat cancer in the 1960s. They re-emerged in the late 1980s and became the first drugs the FDA-approved to treat HIV/AIDS.

Semen directly impairs effectiveness of microbicides that target HIV

Researchers have discovered why microbicides developed to prevent HIV succeed in the lab but fail in clinical trials: Semen. Semen enhances the infectiousness of HIV by causing the virus to cluster together, increasing its ability to attach to and infect cells. This effect is then sufficient to override the antiviral properties of the microbicides.

In the fight against HIV, microbicides -- chemical compounds that can be applied topically to the female genital tract to protect against sexually transmitted infections -- have been touted as an effective alternative to condoms. However, while these compounds are successful at preventing transmission of the virus in a petri dish, clinical trials using microbicides have largely failed. A new study from the Gladstone Institutes and the University of Ulm now reveals that this discrepancy may be due to the primary mode of transportation of the virus during sexual transmission, semen.

"We think this may be one of the factors explaining why so many drugs that efficiently blocked HIV infection in laboratory experiments did not work in a real world setting," explains co-first author Nadia Roan, PhD, a visiting scientist at Gladstone and an assistant professor-in-residence in the Department of Urology at the University of California, San Francisco. "We've shown previously that semen enhances HIV infection, but this is the first time we've shown that this activity markedly reduces the antiviral efficacy of microbicides."

Semen markedly enhances the infectiousness of HIV through the presence of protein aggregates called amyloid fibrils. HIV binds to these fibrils, causing the virus to cluster together and increasing its ability to attach to and infect cells in the host -- in this case the sexual partner of the infected individual. This effect is then sufficient to increase the infectiousness of the HIV virus, thereby diminishing the antiviral properties of the microbicides.

In the study researchers tested the effectiveness of several different types of microbicides targeting the HIV virus on cells that had been exposed to HIV alone compared with cells that were treated with both HIV and semen. Across the board, they saw that not only did the cells with semen have rates of HIV infection approximately ten-fold higher than normal, these microbicides were up to twenty times less effective at blocking the virus in these cells than in those not exposed to semen.

Senior author Jan Munch, PhD, from the University of Ulm says, "Our findings suggest that targeting amyloids in semen is an alternative strategy to improve drug efficacy. The next step is to create a compound or cocktail of drugs that targets both the HIV virus and these amyloid fragments and to test its effectiveness. Also, given that semen is the main means of transmission of HIV, future testing of microbicides in the lab should be performed in the presence of semen to better predict antiretroviral efficacy in real life."

To test that it was the HIV-enhancing ability of semen that was having this effect on the microbicides and not some other substance, the researchers repeated the experiments using semen from men whose semen does not enhance HIV infection due to a disorder called ejaculatory duct obstruction. In the presence of these samples, there was no decrease in effectiveness of the anti-viral microbicides, confirming the importance of the HIV-promoting effects of semen in counteracting the effectiveness of these drugs.

Most microbicides work by targeting the virus itself, attempting to break it down or blocking its ability to infect a cell. However, the heightened infectiousness of HIV in the presence of semen appears to over-power any anti-viral effects the microbicides possess. The one exception to this finding is a different type of microbicide that acts on the host cells' receptors, stopping the virus from latching on from within. In the current study, this microbicide, called Maraviroc, was equally effective in preventing infection both with and without the presence of semen.

"There are important potential clinical implications for this study," says Warner Greene, MD, PhD, director of the Gladstone Institute of Virology and Immunology and a senior author on the paper. "Microbicides were originally developed as a way to empower and protect women in sub-Saharan Africa who often don't have a way to negotiate safe sex or condom use. However, the first generation of microbicides were largely ineffective or worse, some even leading to increased transmission of the virus. This study sheds light on why these microbicides did not work, and it provides us with a way to fix this problem by creating a new compound drug combining antivirals and amyloid inhibitors."

Altered milk protein can deliver aids drug to infants

A novel method of altering a protein in milk to bind with an antiretroviral drug promises to greatly improve treatment for infants and young children suffering from HIV/AIDS, according to a researcher.

That's critical because an estimated 3.4 million children are living with HIV/AIDS, the World Health Organization reports, and nine out of 10 of them live in resource-limited countries in sub-Saharan Africa, where effective antiretroviral treatments still are not widely accessible or available. International medical experts believe less than a third of affected children worldwide receive an antiretroviral drug.

Complicating treatment is that most antiretroviral drugs are not well tolerated by very young children. One of the most commonly prescribed antiretroviral drugs for treating and preventing HIV infection, Ritonavir, has undesirable side effects and important oral-delivery problems. Its physicochemical properties challenge its administration to infants, explained Federico Harte, associate professor of food science.

"Ritonavir has a high hydrophobicity and low solubility in water, which lead to a low dissolution rate in the gastrointestinal fluid and, hence, to insufficient bioavailability. The liquid formulation used to treat infants over one month of age contains 43 percent ethanol and has an awful flavor that has been described as bitter-metallic, medicinal, astringent, sour and burning," he said.

"Moreover, when coming into contact with the stomach mucosa, Ritonavir causes nausea, vomiting and diarrhea. Therefore, we need to develop alternative pediatric formulations of Ritonavir and overcome its poor water solubility to improve its oral administration to infants and children."

To solve that problem, Harte looked to a group of proteins in cow's milk celled caseins. Casein proteins form spherical aggregates called casein micelles, which are responsible, incidentally, for the white color of milk. The casein micelles in mammals' milk are natural delivery systems for amino acids and calcium from mother to young, and Harte reasoned, might deliver Ritonavir molecules as well.

"I have been working with bovine casein micelles for a few years now, and we have investigated the structure and functionality of these proteins," he said. "What we found is these micelles are able to carry molecules that have very little solubility in water, that have low molecular weight and that are very hydrophobic -- such as Ritonavir."

Significantly, Harte discovered in his research that subjecting milk to ultrahigh-pressure homogenization enhances the binding properties of the casein micelles. In previous studies, he learned that casein micelles could be bound to triclosan -- an antimicrobial used in deodorants -- and vitamin D, which is added regularly to skim milk.

Normal milk is homogenized at 10 to 15 megapascals, he pointed out. Milk in this research was homogenized at between 400 and 500 megapascals, disassociating the casein micelles and improving the protein's binding qualities to attach to drug molecules.

"As a result of this enhanced binding of molecules, we believe a milk powder containing Ritonavir can be used as baby formula, providing a transport system for a drug that is not very soluble in water. Right now we are running tests, and we are in the final stages of an experiment in which we gave three different formulations to piglets," Harte said.

"We are taking blood serum samples every three hours to study the kinetics of the drug in the piglets," he said. "The hope is that -- and we don't have the data yet -- we find that the Ritonavir is being adequately delivered by the protein in milk. So if that works, I think we are pretty close to having a formulation that can be used with hydrophobic drugs."

Harte noted that with his proposal for research funding he included a letter from a pediatrician at St. Jude Children's Research Hospital describing the challenge of orally administering Ritonavir to infants and young children.

"She has been treating patients with AIDS, and the awful flavor and ethanol content of Ritonavir were big issues for her," he said. "I am hopeful that this may lead to an application that works against AIDS. We have not done any clinical trials yet, so we will need to get data from those trials to say for sure."

First Immature form of HIV seen at high resolution surprises researchers

The first structure of the immature form of HIV at a high enough resolution has been obtained by researchers, allowing them to pinpoint exactly where each building block sits in the virus. The study reveals that the building blocks of the immature form of HIV are arranged in a surprising way.

Sientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany and collaborators from Heidelberg University, in the joint Molecular Medicine Partnership Unit, have obtained the first structure of the immature form of HIV at a high enough resolution to pinpoint exactly where each building block sits in the virus. The study reveals that the building blocks of the immature form of HIV are arranged in a surprising way.

"The structure is definitely different from what we'd expected," says John Briggs from EMBL, who led the work. "We assumed that retroviruses like HIV and Mason-Pfizer Monkey Virus would have similar structures, because they use such similar building blocks, but it turns out that their immature forms are surprisingly different from each other. At this point, we don't really know why."

Briggs and colleagues used cryo-electron microscopy to study the protein lattice that surrounds the virus' genetic material. After infecting one of the cells in our immune system, HIV replicates, producing more copies of itself, each of which has to be assembled from a medley of viral and cellular components into an immature virus. This is the form that leaves the cell. The protein building blocks that make up the virus are then rearranged into the virus' mature form, which can infect other cells.

The first cryo-electron microscopy images of immature HIV, obtained at EMBL in the 1990s, surprised researchers by showing that the virus did not have a regular symmetrical structure, as had been assumed. That meant it was going to be difficult to get a detailed picture of the structure of its protein lattice. Two decades on, by optimising both how data is collected at the microscope and how it is analysed, Florian Schur, a PhD student in Briggs' lab, has now achieved an unprecedentedly detailed structure.

With this structure in hand, scientists have a basis to probe further. They can use it to decide where to focus efforts for achieving the even greater detail needed to explore potential drug targets, for instance. It will also enable researchers to understand how mutations might influence how the virus assembles. And the techniques themselves can be applied to a variety of questions.

"This approach offers so many possibilities," says Schur. "You can look at other viruses, of course, but also at complexes and proteins inside cells, with a whole new level of detail."

In future, the EMBL scientists will use the approach to look at other viruses and at the vesicles that transport material inside cells. They also aim to push the techniques even further, to allow them to see other parts of the viral proteins that are currently beyond their reach, but which they suspect play an important role in HIV maturation.

"In the long term, we'd also like to investigate how drugs which are known to inhibit virus assembly and maturation actually work," Briggs concludes.

Can social media help stop the spread of HIV?

In addition to providing other potential benefits to public health, all of those tweets and Facebook posts could help curb the spread of HIV. Although public health researchers have focused early applications of social media on reliably monitoring the spread of diseases such as the flu, a new article tells of a future in which social media might predict and even change biomedical outcomes.

Although public health researchers have focused early applications of social media on reliably monitoring the spread of diseases such as the flu, Sean Young of the Center for Digital Behavior at the University of California, Los Angeles.

"We know that mining social media will have huge potential benefits for many areas of medicine in the future, but we're still in the early stages of testing how powerful these technologies will be," Young said.

With the right tools in place, he says, social media offers a rich source of psychological and health-related data generated in an environment in which people are often willing to share freely.

His recent work on Behavioral Insights on Big Data (BIBD) for HIV offers the tantalizing possibility that insights gleaned from social media could be used to help governments, public health departments, hospitals, and caretakers monitor people's health behaviors "to know where, when, and how we might be able to prevent HIV transmission."

Young details a social-media-based intervention in which African American and Latino men who have sex with men shared a tremendous amount of personal information through social media, including when or whether they had 'come out,' as well as experiences of homelessness and stigmatization. What's more, they found that people who discussed HIV prevention topics on social media were more than twice as likely to later request an HIV test.
In the context of HIV prevention, tweets have also been shown to identify people who are currently or soon to engage in sexual- or drug-related risk behaviors. Those tweets can be mapped to particular locations and related to actual HIV trends.

What's needed now is the updated infrastructure and sophisticated toolkits to handle all of those data, Young said, noting that there are about 500 million communications sent every day on Twitter alone. He and a team of University of California computer scientists are working to meet that challenge now.
Although privacy concerns about such uses of social media shouldn't be ignored, Young says there is evidence that people have already begun to accept such uses of social media, even by corporations looking to boost profits.

"Since people are already getting used to the fact that corporations are doing this, we should at least support public health researchers in using these same methods to try and improve our health and well being," he said. "We're already seeing increased support from patients and public health departments."

Real-life social networking prompts people to get tested for HIV

Old-school face-to-face social networking is a more effective way to identify people with HIV than the traditional referral method, suggests research. The study shows that social networking strategies - enlisting people in high-risk groups to recruit their peers to get tested – is more efficient and targeted than traditional testing and referral programs, resulting in 2-and-a-half times more positive test results.

As many as 20 percent of HIV-positive people are unaware of being infected with the virus, and therefore do not receive vital treatment. In addition to missing out on medications that can improve their prognosis and quality of life, these patients also are more likely to spread the disease to others. Therefore, encouraging people at risk for HIV to get tested is critical.

SNS programs likely are more effective because they are more proactive than traditional counseling, testing and referral (CTR) programs, which are available to anyone who wishes to be tested but do not offer the same motivation as encouragement by peers.

"A limitation of the traditional approach is that many people who are at high risk of HIV never take the initiative to get tested on their own," said Ryan Westergaard, MD, PhD, MPH, lead author of the study and assistant professor of medicine at the University of Wisconsin School of Medicine and Public Health, Madison. "Our study found that using social network strategies, in which we enlist people at high risk to encourage peers in their social networks to get tested, results in a higher proportion of positive HIV tests - making our efforts more effective and allowing us to reach the people who need it most."

In the study, researchers collected data from 45 HIV testing sites in Wisconsin over four years. Through SNS, 54 of 2,169 (2.49 percent) people tested were HIV-positive vs. 440 of 48,318 (.91 percent) of those tested through CTR.

In SNS - which is growing in large cities - people at high risk for HIV are paid an incentive (typically $10 to $20) for every person they refer who gets tested. Some experts are concerned that these programs are costly, but the new research suggests that SNS is worthwhile, because it results in a higher percentage of positive tests.

"Some SNS programs limit the numbers of people a recruiter can refer for testing, based on the assumption that that they're just signing up everyone they know to make more money, even if they're unlikely to be HIV-positive," said Dr. Westergaard. "Our study showed that, on average, the 30th or 40th person referred for testing through SNS had just as high if not a higher probability of having a positive HIV test than the first five or 10 people referred.This suggests SNS can be a cost-effective tool to increase testing in specific high risk pools, such as men who have sex with men and transgender people."

Antiretroviral therapy benefits HIV-infected stimulant users

New clinical research from UC San Francisco shows that 341 HIV-infected men who reported using stimulants such as methamphetamine or cocaine derived life-saving benefits from being on antiretroviral therapy that were comparable to those of HIV-infected men who do not use stimulants.

That said, those who reported using stimulants at more than half of at least two study visits did have modestly increased chances of progressing to AIDS or dying after starting antiretroviral therapy compared to non-users. The data was collected between 1996 and 2012.

"Patients with HIV who use stimulants and other substances often experience difficulties with accessing antiretroviral therapy, partially due to the concerns of healthcare providers that they will not be able take their medications as directed. Findings from this study demonstrate that many stimulant users take their antiretroviral therapy at levels sufficient to avoid negative clinical outcomes. When we look at overall mortality, antiretroviral therapy leads to similar clinical benefits for both stimulant users and non-users, notwithstanding stimulant use," said the study's primary investigator, Adam W. Carrico, PhD., UCSF assistant professor of nursing.

The study included 1,313 HIV-infected men who have sex with men within the Multicenter AIDS Cohort Study, an ongoing nationwide prospective study of HIV infection among men who have sex with men in the U.S.

"If we are to achieve the goals of the President's National HIV/AIDS Strategy and UNAIDS to end the HIV/AIDS epidemic, we will need to treat HIV-positive active substance users for their HIV while encouraging them to stop or reduce their substance use. Programs integrating substance abuse services with HIV clinical care may both improve health outcomes for patients and reduce new infections," said Carrico.

The UCSF Division of HIV/AIDS at San Francisco General Hospital has created an integrated care delivery system that could serve as a model for other clinics, added Carrico. The HIV primary care clinic utilizes a patient centered team care approach that includes substance abuse services for stimulant and opioid users, along with mental health services, all located onsite. STOP, the "stimulant treatment outpatient program," within the clinic provides outpatient substance abuse and mental health treatment integrated with patients' primary medical care.

"The pattern of use varies and the real issue is whether patients can take their antiretrovirals as prescribed. We find that some patients are able to start taking antiretrovirals very reliably before they are able to decrease or stop their stimulant use, which often requires more complex behavioral, emotional, interpersonal and environmental changes. Being in an HIV primary care setting allows us to engage stimulant users even if they are not ready to go to specialty substance abuse programs or support groups," said Valerie Gruber, PhD, STOP director and UCSF professor of psychiatry.

Could there be an end in sight for AIDS?

South Africa is the epicentre of the HIV and AIDS epidemic with a staggering 6.4 million HIV infected citizens. In 1990 the WHO reported just 386 cases in South Africa. Over the next 15 years, despite warnings from scientists and policy makers, a tidal wave of infections ensued.  How can policy and health provision cope to improve the outlook?  A new article strategically examines the whole epidemic and identifies economic, epidemiological, and programmatic points for transition and future improvement.

Until 2001, HIV infection in the developing world amounted to certain death for all but the wealthiest. Development of Antiretroviral (ART) drugs now gives an infected young adult a life expectancy of 60. A massive break through, but each patient needs drugs for up to 30 years, representing a huge burden of cost and an enduring challenge for government and health providers to manage. The high cost of drugs may over reach the South African national health budget in a very few years. New infections outnumber AIDS deaths, increasing the number of people living with AIDS; patients requiring treatment increase faster than funding and the scenario escalates. Can the epidemic ever be managed out of an emergency into a more controlled state?

Prevention is central; only by reducing the rate of new infections can an eventual decline in HIV sufferers be achieved; an economic transition. After this tipping point those newly receiving treatment can outpace new infections; an epidemiological transition. In 2006 programmatic transition took place when newly initiated ART patients exceeded numbers of new patients needing ART. Sustained commitment to prevention and treatment has undoubtedly resulted in attrition of untreated HIV/AIDS patients. In future ART is proposed for a wider group of HIV patients, which the WHO believes will prevent 3 million deaths and 3.5 million new infections. It is clear though that despite this, AIDS and the financial load of ART will be here for many more generations, even if infection rates are brought under control.

The authors note "Although significant progress has been made in combating HIV and AIDS, the end of the epidemic may still be a long way off. However, sustained efforts to expand prevention and treatment programmes, as well as health systems strengthening and innovative financing, will ensure the long-term impact of these transitions."

Stem cell transplant does not cure SHIV/AIDS after irradiation of infected rhesus macaques

A new study reports a new primate model to test treatments that might cure HIV/AIDS and suggests answers to questions raised by the "Berlin patient," the only human thought to have been cured so far.

Being HIV-positive and having developed leukemia, the Berlin patient underwent irradiation followed by a bone-marrow transplant from a donor with a mutation that abolishes the function of the CCR5 gene. The gene codes for a protein that facilitates HIV entry into human cells, and the mutation - in homozygous carriers who, like the donor, have two defective copies - protects against HIV infection.

Several factors could have contributed to the cure of HIV/AIDS in the patient:

1. the ablation of blood and immune cells following irradiation killed all or many of the viral reservoir cells that are not eliminated by antiretroviral treatment (ART);
2. the CCR5 deletion mutation in the donor cells protected them and their progeny from HIV infection;
3. a "graft versus host" reaction occurred, where the transplanted cells and their progeny recognize the host cells as foreign and attacked and eliminated HIV-positive reservoir cells that survived the irradiation.

Guido Silvestri, from Emory University in Atlanta, USA, and colleagues investigated the relative contribution of the irradiation to eliminate the reservoir of HIV-infected cells. The scientists worked with the animal model of Simian Immunodeficiency Virus (SIV, a close relative of HIV that infects primates and causes a disease similar to AIDS) infection in rhesus macaques. Using a total of six monkeys (three of which served as controls and did not receive transplants) they performed, for the first time, hematopoietic stem cell transplantation in rhesus macaques infected with a chimeric simian/human immunodeficiency virus (SHIV) and treated with ART.

The researchers harvested hematopoetic stem cells from three macaques prior to infection (of all six animals) with SHIV. They also treated the macaques with ART to reduce viral load and mimic the situation in human HIV-infected patients on ART. They then exposed the three monkeys from which they had collected hematopietic stem cells to a high dose of radiation. This killed most of their existing blood and immune cells, including between 94 and 99% of their CD4-T cells -- the main target of HIV infection -- in the blood. The irradiation was followed by transplantation of each monkey's own virus-free hematopoietic stem cells. The latter can regenerate the blood and immune cells, and did so in all three monkeys within 3 to 6 weeks. Because the transplanted cells are not from a different donor, no graft versus host disease would be expected, and none was observed.

After that time, the scientists stopped ART in all six monkeys. As expected, the virus rebounded rapidly in the control animals. Of the three transplanted animals, two also showed a rapid rebound. The third monkey developed kidney failure two weeks after ART was stopped and was euthanized. It still had undetectable levels of virus in the blood at that time, but post-mortem analysis showed low levels of viral DNA in a number of tissues, arguing that none of the three transplanted monkeys was cured.

The researchers acknowledge a number of limitations of the study, including the small number of monkeys, and the relatively short period of ART prior to irradiation and transplantation. Nonetheless, they say their study "supports the hypothesis that myeloablative total body irradiation can cause a significant decrease in the viral reservoir in blood cells, even though it was not sufficient to eliminate all reservoirs." Their results, they say, suggest that in the cure of the Berlin patient, "the use of the CCR5 mutant donor and/or the presence of graft versus host disease played a significant role."

Having demonstrated in this first test-of-concept study that total body irradiation and hematopoietic stem cell transplantation in ART-treated SIV-infected rhesus macaques is feasible, the researchers express hope that "further studies using this model will provide critical information for the requirements to cure HIV infection in humans."

HIV antibody discovered that binds to novel target on virus

An NIH-led team of scientists has discovered a new vulnerability in the armor of HIV that a vaccine, other preventive regimen or treatment could exploit. The site straddles two proteins, gp41 and gp120, that jut out of the virus and augments other known places where broadly neutralizing antibodies (bNAbs) bind to HIV. This newly identified site on the viral spike is where a new antibody found by the scientists in an HIV-infected person binds to the virus. Called 35O22, the antibody prevents 62 percent of known HIV strains from infecting cells in the laboratory and is extremely potent, meaning even a relatively small amount of it can neutralize the virus.

Following their discoveries, the scientists found that 35O22-like antibodies were common in a group of HIV-infected people whose blood contained antibodies that potently neutralized a broad array of HIV strains. According to the researchers, this suggests that it might be easier for a vaccine to elicit 35O22 than some other known bNAbs, which are less common.

Since 35O22 binds only to forms of the viral spike that closely resemble those that naturally appear on HIV, the scientists believe a vaccine that elicits 35O22-like antibodies would need to mimic the natural shape of the spike as closely as possible. This would require a different approach than that used in many previous experimental HIV vaccines, which have included just parts of the viral spike rather than a structure that looks like the entire native viral spike.

In addition, the researchers report, the HIV strains that 35O22 neutralizes complement strains neutralized by other bNAbs. This suggests that eliciting or combining 35O22 with a few other bNAbs in a vaccine or a prevention or treatment regimen could likely neutralize the vast majority of HIV strains found around the globe, according to the scientists.