• Several rumours have been circulating about the vaccine’s effects on fertility
• Professor Lucy Chappell has reassured there is ‘absolutely no basis for concerns’
• However, she added that pregnancy, the new virus and vaccines are ‘a constantly evolving area’ which needs further research 

After months of anticipation, the first Covid-19 vaccines finally started being administered in the UK last month. 

Amid the rollout, several rumours and myths have been circulating about the vaccine, including fears that the jab could affect fertility. 

Now, Professor Lucy Chappell, NIHR Research Professor in Obstetrics at King’s College London, is attempting to reassure women that the Covid-19 jab will not affect their fertility. 

Her advice comes shortly after a poll of 55,642 Brits found that more than a quarter of 18-to-34-year-old women said they would say no to the jab, citing concerns over the vaccine’s effect on fertility and pregnancies. 

Professor Chappell says it is understandable that there have been questions about the new vaccines but notes that fearful claims which can be easily found online have never been substantiated.

‘I dug into all those sources and I can see absolutely no basis for concerns about any of the Covid-19 vaccines that are licensed in the UK and fertility,’ she told the PA news agency.

She described the claims as ‘spurious’ because they relate to similarities between some aspects of the proteins involved in fertility and the Covid-19 vaccines, but these are ‘very speculative and entirely not supported by any of the data’.

There is no concern from a biological point of view and evidence has not been presented that women who have been vaccinated have gone on to have fertility problems, she said.

Pregnancy, the new virus and vaccines are ‘a constantly evolving area’ which needs further research, as there is very limited experience in trials on pregnant women, according to Prof Chappell.

She hopes that vaccine companies may change this situation in the future.

Women who are in the highest risk Covid-19 groups, such as carers and health workers or the clinically extremely vulnerable such as those with underlying health conditions, should try to have ‘a sensible discussion’ about their concerns about the jab.

They are among the first phase of people to be vaccinated and their obstetrician or midwife is the obvious person to try and seek useful information from.

Prof Chappell suggested that ‘we may be in a different place in six months in terms of how we can have those discussions’ as new and updated information comes through from the real-life current use of vaccines.

Bigger trials are needed involving pregnant women to help answer questions about safety and risk but how the woman views her risk of exposure and complications is an important factor that needs to be taken into the mix.

Prof Chappell said there are ‘very clear checks and balances’ involving the women who take part in research trials.

Professor Chappell’s advice comes shortly after a poll revealed that young women are the most likely to turn down the Covid-19 vaccine.

The Find Out Now poll, which sampled 55,642 people, found that more than a quarter of 18-to- 34-year-old women said they would say no to the jab, citing their concerns over the vaccine’s effect on fertility and pregnancies.

By contrast, only seven per cent of those aged 65 and over said the same. 

WHY CAN’T PREGNANT WOMEN HAVE THE COVID-19 VACCINE? 

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COVID-19 poses the greatest threat to older people, but vaccines often don’t work well in this group. Scientists hope drugs that rejuvenate the immune system will help.

Unlike fine wine, the human body does not improve with age. Hearing fades, skin sags, joints give out. Even the body’s immune system loses some of its vigour.

This phenomenon, known as immunosenescence, might explain why older age groups are so hard-hit by COVID-19. And there is another troubling implication: vaccines, which incite the immune system to fight off invaders, often perform poorly in older people. The best strategy for quelling the pandemic might fail in exactly the group that needs it most.

Scientists have known for decades that ageing immune systems can leave the body prone to infection and weaken their response to vaccines. In June, the US Food and Drug Administration announced that a COVID-19 vaccine would have to protect at least half the vaccinated individuals to be considered effective, but protection in older adults might not even meet that bar. “No vaccine is going to be as effective in the elderly as it is in young people,” says Matt Kaeberlein, a gerontologist at the University of Washington in Seattle. “That’s an almost certainty.”

The human immune system is mind-bendingly complex, and ageing affects nearly every component. Some types of immune cell become depleted: for example, older adults have fewer naive T cells that respond to new invaders, and fewer B cells, which produce antibodies that latch on to invading pathogens and target them for destruction. Older people also tend to experience chronic, low-grade inflammation, a phenomenon known as inflammageing (see ‘Depleted defences’). Although some inflammation is a key part of a healthy immune response, this constant buzz of internal activation makes the immune system less responsive to external insults. “This overarching, chronic inflammatory state is what’s driving much of the immune dysfunction that we see,” says Kaeberlein. The upshot is a poorer reaction to infections and a dulled response to vaccines, which work by priming the immune system to fight off a pathogen without actually causing disease.

With about 50 COVID-19 vaccine candidates currently being tested in humans, researchers say it’s not yet clear how they will fare in older adults. In its phase I study of 40 people aged 56 and over, Moderna in Cambridge, Massachusetts, reported that its candidate mRNA-1273 elicited similar antibody levels as those elicited in a younger age group¹. The Chinese biotech Sinovac in Beijing, which trialled its CoronaVac candidate in a phase I/II study that included 421 adults between 60 and 89 years of age, announced in a press release on 9 September that it seems to work as well in older adults as it does in younger ones. However, a phase I study by international pharma company Pfizer and BioNTech in Mainz, Germany, showed that their vaccine BNT162b2 provokes an immune response that is about half as strong in older adults as it is in younger ones². The older adults still produced more antibodies in response to the vaccine than people of a similar age who had had COVID-19, but it’s not known how these levels translate into protection from the virus.

Most COVID-19 vaccine trials include at least some older adults. But a recent analysis of 18 such trials found that the risk of exclusion is high³. More than half had age cut-offs and many were at risk of excluding older participants for other reasons, including underlying conditions.

If COVID-19 vaccines perform less well in older adults, researchers might be able to find ways to tweak the shot itself to elicit a stronger response. Some influenza vaccines, for instance, include immune-boosting ingredients or higher doses of the viral antigen. But some scientists say there is a better option. They are developing and testing drugs that could improve how older adults respond to vaccines and might also help them fight viruses more effectively in the first place. Rather than working with the limitations of the ageing immune system, they are planning to rejuvenate it.

Forever young

Many researchers have grown old trying to pinpoint ways to reverse the ageing process. In the past decade, however, they have made serious progress in identifying particular molecular targets that might help in this quest.

One promising class of anti-ageing drug acts on pathways involved in cell growth. These drugs inhibit a protein known as mTOR. In the laboratory, inhibiting mTOR lengthens lifespan in animals from fruit flies to mice. “mTOR is one of probably multiple biologic mechanisms that contribute to why we age and why our organ systems start to decline,” says Joan Mannick, co-founder and chief medical officer of resTORbio, a biotech company based in Boston, Massachusetts, that aims to develop anti-ageing therapies.

In a study published in 2018 and carried out when Mannick was at the Novartis Research Institutes in Cambridge, Massachusetts, she and her colleagues tried damping down mTOR in elderly adults to see if this could improve immune function and lower infection rates⁴. The 264 participants received a low-dose mTOR inhibitor or a placebo for six weeks. Those who received the drug had fewer infections in the year after the study and an improved response to the flu vaccine. On the basis of her work on mTOR inhibition, Mannick, by then at resTORbio, launched a phase III trial in 2019 to see if a similar mTOR inhibitor called RTB101 could stave off respiratory illnesses in older adults.

That trial failed to show the desired effect, perhaps because infections were monitored by self-report of symptoms rather than requiring a lab test to confirm infection, as in the earlier trial. That created “a lot more noise”, says Ilaria Bellantuono, co-director of the Healthy Lifespan Institute at the University of Sheffield, UK, who was not involved in the trial. “A much bigger group would have been required to see a difference.”

Still, the data from this and an earlier trial suggested that participants who received the mTOR inhibitor had fewer severe infections from circulating coronaviruses and recovered faster from them than the placebo group. The trials pre-date the emergence of SARS-CoV-2, but they suggest that RTB101 could lessen the severity of infection. resTORbio is now testing that idea in 550 nursing-home residents aged 65 and over.

RTB101 is similar to an already approved mTOR inhibitor, the immune-suppressing drug rapamycin. At least four other groups are testing rapamycin in small numbers of infected individuals as a possible COVID-19 therapy; one group is trialling the drug exclusively in adults aged 60 or older.

The type 2 diabetes drug metformin also dampens down mTOR’s activity, albeit indirectly. Some studies suggest that people who take metformin are less likely to be hospitalized or die if they contract COVID-19. A small retrospective study in China found that the mortality among hospitalized individuals with COVID-19 taking metformin was 2.9% compared with 12.3% in people who didn’t take the drug⁵. Researchers at the University of Minnesota in Minneapolis analysed data on hospitalized individuals with COVID-19 who had an average age of 75, some of whom were already taking metformin for obesity or diabetes. They found a significant reduction in mortality among women taking metformin, but not among men⁶.

Carolyn Bramante, an obesity researcher who led the University of Minnesota study, points out that diseases such as diabetes and obesity lead to some of the same immune deficits as occur in older age. She and her colleagues plan to launch a trial of 1,500 people aged 30 and over to determine whether metformin could help stave off SARS-CoV-2 infection or prevent the worst outcomes in people already infected.

Meanwhile, Jenna Bartley, who studies ageing at the University of Connecticut in Storrs, is assessing whether metformin can boost responses to flu vaccine in a small trial of older adults. The idea, based on her work in mice, is that metformin can improve the energy metabolism of the T cells of the immune system, making them better at detecting new threats. Bartley has finished collecting data, but because her lab was shut down owing to COVID-19, she won’t have the results analysed for a few more weeks.

If metformin works against COVID-19, researchers will still have to tease out why. Kaeberlein points out that no one is quite sure how metformin works because it has so many targets. “It’s about the dirtiest of dirty drugs out there,” he says. It was originally used as an anti-influenza drug; Bramante says it helps tamp down inflammation. Aside from the mechanistic unknowns, the advantage is that metformin has been used for decades and is generally safe. Children can take it, as can pregnant women. “Metformin is a medication that you actually could give prophylactically for 12 months without having to do any follow-up,” Bramante says, “and it costs less than US$4 a month.”

Soothing balm

mTOR is a classic anti-ageing target, but it’s far from the only one. In fact, many anti-ageing pathways seem to be linked, says James Kirkland, who studies cellular ageing and disease at the Mayo Clinic in Rochester, Minnesota. “That is, if you target one, you tend to affect all the rest,” he says. Many of the immune changes that come with ageing lead to the same result: inflammation. So researchers are looking at drugs that will calm this symptom.

Arne Akbar, an immunologist at University College London, has shown that the anti-inflammatory drug losmapimod, which is being developed as a therapy for muscular dystrophy, might help boost immunity. In a 2018 study, the researchers injected chickenpox virus into the skin of elderly adults⁷. Although these people had already been exposed to chickenpox, their immune response was lacklustre, hampered by excess inflammation. When the team gave the study participants losmapimod, it ratcheted down inflammation by about 70% and improved their immune responses.

In June, the company currently developing losmapimod — Fulcrum Therapeutics in Cambridge, Massachusetts — launched a 400-person phase III study to investigate whether the drug could prevent death and respiratory failure in older people hospitalized with COVID-19.

“Senescence is really a key factor in ageing,” says Eric Verdin, president and chief executive of the Buck Institute for Research on Aging in Novato, California, who is not involved in the fisetin research. No senolytics have currently been approved for clinical treatment, however. “This is one area that has been much less studied,” he says.

Kaeberlein says it’s likely that most companies will pursue anti-ageing drugs as therapies before they test them as prophylactics. “It’s much easier to get a therapy approved in people who are already sick,” he says. He thinks that mTOR inhibitors hold the most promise. “If I had the power to go back to the beginning of this whole COVID pandemic and try one thing, I’d pick mTOR inhibitors — rapamycin specifically,” he says. According to his back-of-the-envelope calculations, if rapamycin works in the same way in people as it does in mice, it could reduce COVID-19 mortality by 90%.

Kirkland says he can envisage giving one of these anti-ageing drugs as a primer before vaccination. “We have to figure out ways to target fundamental ageing mechanisms at around the time that we’re vaccinating people,” he says, “but we have to find ways of doing this that are safe and effective.”

Added ingredients

If tweaking the immune system proves too challenging, there might be ways to juice up the vaccine itself. For flu, there are two vaccines aimed specifically at people over 65, which help worn immune systems to stage a response. One, Fluzone High-Dose, contains four times the standard amount of flu virus antigens, and the other, Fluad, relies on an immune-boosting molecule called an adjuvant.

A team led by vaccinologist Ofer Levy at Boston Children’s Hospital in Massachusetts is working on a COVID-19 vaccine specifically for older adults, using an in-vitro screening system to identify the best adjuvants. “Vaccines were typically developed as one-size-fits-all,” he says. But a lot of features — age, sex, and even the season — affect vaccine responses, Levy says. The best combinations of adjuvant and vaccine they find will be tested in mice and then in humans.

But, in general, developing medications to improve immune function seems like a much smarter strategy than creating vaccines specifically for elderly people, says Claire Chougnet, an immunologist at Cincinnati Children’s Hospital Medical Center in Ohio, who is studying inflammation in aged mice. Vaccine development is costly and time-intensive. “In the case of an emerging virus, when you want a quick response, that makes things even more complicated if you have to do two types of vaccine,” she says. Plus, individual vaccines target specific pathogens, but an immune-boosting medication could be used with any vaccine. “That could work for flu, that could work for COVID-19. That would work for COVID-25,” she says. The approach is “extremely versatile”.

Verdin agrees that supporting the older immune system should be a priority. “I think the net result of all this will be renewed interest in understanding the defect in the immune response in the elderly.” That has implications not only for the coronavirus, but also for a host of other diseases, including other viral infections and even cancer. “COVID-19 has brought to the front something that a lot of people have ignored.”

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New Delhi: In a significant development towards diabetes treatment and prevention, researchers at Karolinska Institutet and their colleagues at Tampere University and University of Jyväskylä in Finland have developed a vaccine against viruses linked to type 2 diabetes. Research has shown that certain virus infections may play a part in autoimmune attack that results in the development of type 1 diabetes. The major discovery came amid global race to find a cure for coronavirus that has resulted in an unprecedented public health crisis.

Currently, there’s no definitive way to prevent type 1 diabetes, also known as juvenile diabetes as it’s usually diagnosed in children, teens and young adults. However, the condition can be managed through a combination of medications and lifestyle changes.

Vaccine may offer protection against type 1 diabetes

According to the study published in the scientific journal Science Advances, coxsackievirus B (CVB) enteroviruses are common human pathogens known to cause severe diseases such as myocarditis, chronic dilated cardiomyopathy, and aseptic meningitis. These viruses are also hypothesised to be a causal factor in type 1 diabetes. No vaccine is available yet for CVBs, which comprises of six strains that can also cause the common cold.

Epidemiological studies suggest that CVBs could be a pathogenic contributor. Autopsy observations also indicate that CVBs might be involved in the development of type 1 diabetes. However, this remains hypothetical and more research is required to prove the connection – though this hypothesis is a well-established amongst diabetes researchers.

In the current research, the team at Karolinska Institutet and their colleagues at Tampere University and University of Jyväskylä in Finland produced a vaccine that protects against all six known strains of CVB. Tests conducted in different animal models showed that the vaccine can protect mice infected with CVB from developing virus-induced type 1 diabetes.

The vaccine was tested in rhesus monkeys that have very similar genetics to humans. The researchers observed that the vaccine produced encouraging results and induced antibodies to CVB, suggesting it could protect against the virus.

“The results give important scientific support to an ongoing clinical development program aiming at testing a similar commercial vaccine in humans,” says Professor Heikki Hyöty from Tampere University who participates in the clinical development program, which is carried out by an American pharmaceutical company in collaboration with a Finnish biotech company.

The team now plans to test the vaccine on children with a genetic risk profile for type 1 diabetes, assuming that the medication is safe in initial clinical trials. According to the researchers, CVBs can be confirmed as a triggering environmental factor if the number of children that develop type 1 diabetes decreases after vaccination or if none develop the condition.

KEY HIGHLIGHTS

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An experimental HIV vaccine developed by scientists at Scripps Research and the nonprofit vaccine research organization IAVI has reached an important milestone by eliciting antibodies that can neutralize a wide variety of HIV strains.

The tests, in rabbits, showed that these “broadly neutralizing” antibodies, or bnAbs, targeted at least two critical sites on the virus. Researchers widely assume that a vaccine must elicit bnAbs to multiple sites on HIV if it is to provide robust protection against this ever-changing virus.

The promising results, which appear in Immunity, suggest that researchers are one step closer to developing an effective HIV vaccine—a major goal of medical science ever since the virus was identified in 1983.

“It’s an initial proof of principle but an important one, and we’re now working to optimize this vaccine design,” says the study’s senior author Richard Wyatt, Ph.D., a professor in the Department of Immunology and Microbiology at Scripps Research.

According to UNAIDS, about 35 million people worldwide have died of the immunodeficiency syndrome, AIDS, which is caused by HIV infection. About 38 million others are now living with HIV infection. Antiviral drugs can keep HIV-infected people alive and reduce their ability to transmit the virus to others, but these drugs do not clear the infection and must be taken indefinitely. Researchers have long recognized that a preventive vaccine, available at a low cost to uninfected people, will be needed to eliminate HIV as a major public health threat.

HIV’s rapid mutation rate and other mechanisms for evading immune attack have made it an extremely difficult target for vaccine designers. But the test conducted by Wyatt and his team confirms that vaccination can elicit the kinds of antibodies that are needed to provide broad protection against HIV. These bnAbs, as vaccine experts call them, can neutralize multiple HIV strains because they bind to critical sites on the virus that do not vary much from strain to strain. People who are infected with HIV sometimes produce bnAbs as part of their antibody response, but infrequently and usually after infection has been long established. The chief challenge for HIV vaccine designers has been to find ways to stimulate the immune system—in most or all individuals—into making bnAbs that hit multiple vulnerable sites on the virus, in order to protect against a high proportion of HIV strains.

At the heart of the vaccine design by Wyatt and colleagues is a virus-mimicking protein based on HIV’s “Env” protein. Normally, multiple copies of bush-like Env proteins are spread out on the surface of each spherical HIV particle. Each Env protein contains a molecular mechanism that allows it to bind to a receptor on immune cells known as CD4, and use that receptor as a portal to break into the cell. The researchers engineered a version of Env that models the essential structures on the real Env while being stable enough to use as a vaccine. To present it in a way that would resemble a real HIV virus particle, they created virus-sized synthetic spheres of fat-related molecules, “liposomes,” which are studded densely with the engineered Env proteins.

On a natural HIV Env protein, thickets of sugar-related molecules called glycans normally help shield the all-important CD4 binding site from immune attack. As an initial “priming” immunization, the researchers used versions of Env in which this glycan shield around the CD4 binding site had been partly removed.

“The idea was to better expose this site and thereby stimulate a broad antibody reaction to it at the start,” Wyatt says.

Subsequent booster immunizations over 48 weeks used Env proteins with restored glycans, to select for antibodies that target the CD4 binding site but can also get through this shield. The Env proteins in the booster shots also were mixes based on different strains of HIV, to generally promote antibody responses against Env structures that do not vary among these strains.

The team inoculated 12 rabbits following their vaccine strategy and compared the results with a control group that received only a single, glycan-shielded version of Env. They found that their vaccine strategy had a much better response, with five of the rabbits developing antibodies that could neutralize multiple HIV isolates.

The researchers analyzed the antibodies of the rabbit that had responded most strongly, and identified two distinct types of bnAb. One, which they called E70, blocks the CD4 binding site as expected, though in an unusual way—partly by grabbing one of the shielding glycans. The other, 1C2, hits a different but well known vulnerable spot on Env, at the interface between two key segments of the complex protein. The binding of antibody 1C2 apparently destabilizes Env so that it can no longer mediate HIV’s entry into host cells. That antibody also turned out to have an unusual breadth of neutralization, blocking 87 percent of a panel of 208 distinct HIV isolates.

The finding is an important demonstration that vaccination against HIV, if done in the right way, can achieve the goal of inducing bnAbs to multiple sites on the virus, Wyatt says.

The team of scientists are continuing to test and improve their vaccine strategy in small animal models and hope eventually to test it in monkeys and then humans.

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Remember the landmark RV144 study in Thailand a decade ago that was the first clinical trial to show any efficacy of a vaccine for preventing HIV infection? Now, a team of scientists led by the Fred Hutchinson Cancer Research Center and the University of the Witwatersrand in Johannesburg has found the same regimen can also induce promising immune responses in South Africans, suggesting the vaccine may have the potential to protect against multiple strains of HIV.

In Thailand, the predominant HIV strain is clade B, while clade C is the most common subtype in South Africa. In the new trial, scientists found the RV144 vaccine—containing constructs of HIV clades B and E inserts—showed even higher cellular and humoral immune responses in healthy people in South Africa than in RV144’s Thailand vaccines, according to results published in Science Translational Medicine.

HIV is notorious for its diversity and tendency to mutate, which already makes treating the virus difficult. The same challenge holds true for vaccine development. That’s why the Fred Hutchinson-led team set out to test the RV144 regimen in South Africa and compared immunogenicity data to those from the Thailand study.

One hundred healthy adults participated in the trial, and 91 received all four vaccinations. The researchers evaluated the magnitude and frequency of several immune responses that correlate to infection risk.

Specifically, the vaccine induced strong CD4+ T cells directed at HIV envelope proteins in 51.9% of South Africans, significantly higher than the 36.4% seen in the Thailand trial. And the South Africans’ T cells also scored better on a functionality assay that evaluates how good the cells are at producing cytokines.

They looked at the immunoglobulin G (IgG) antibody responses, and participants in the current trial performed better across the board than those from the original RV144 study. They also examined the antibody-dependent cellular cytotoxicity (ADCC), in which immune cells rupture the target cell. Previously, the efficacy of RV144 was correlated with ADCC. Turns out, 72.6% of the trial participants in South Africa responded in the current trial, versus 58.5% of those in Thailand

Back in 2009, RV144 showed just 31.2% effectiveness by month 42. Since then, a variety of research teams have been trying to achieve better protection against as many strains of HIV virus as possible. Scientists led by Duke University previously built on the regimen by adding three more targets to the vaccine construct, making it a pentavalent vaccine. In a study in monkeys, the vaccine achieved 55% protection. Johnson & Johnson recently started testing a different HIV vaccine in a 3,800-person late-stage clinical trial.

The newly reported trial was a precursor to a trial that tested an adapted regimen including subtype C antigens and an adjuvant from GlaxoSmithKline in 252 South African participants. Based on positive interim results from HVTN 100, the National Institutes of Health pushed the new regimen into a large-scale trial that aims to enroll 5,400 men and women, also in South Africa.

The Fred Hutchinson and Johannesburg team did report that the T-cell and antibody responses dropped over time during the trial, “suggesting the utility of additional boosts,” they argued in the study.

But the vaccine’s ability to provide protection against multiple strains of HIV was key, they added. “Our data suggest that the breadth of immune responses elicited by this vaccine regimen may allow for vaccine protection that could extend beyond the clade used for immunogen development, and potentially function as a more global vaccine,” they wrote in the study.

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Vaccines are humanity’s biggest achievement against infectious diseases. But could they defeat HIV, a particularly crafty virus? José Luis Cabero, CEO of Spanish biotech AELIX Therapeutics shared his experience developing an HIV vaccine at Labiotech Refresh in Barcelona.

The concept of a vaccine is simple — priming the immune system against a pathogen so that it is prepared to fight off the real thing. This simple principle has been one of humanity’s greatest weapons against disease, with achievements including the total eradication of smallpox and severely limiting the damage caused by polio and measles.

“If you take a look at vaccines as a whole, they’re the most successful medical intervention ever,” said José Luis Cabero, CEO of AELIX Therapeutics. “There’s no medical intervention that’s been as impactful on mankind as vaccination.”

Having spent a lot of his career in companies developing vaccines, Cabero turned his sights to a new target when he joined AELIX in 2017. Founded in 2015, the company aims to develop a therapeutic vaccine for HIV, a particularly formidable foe.

Back in the 1980s, an HIV infection was essentially a death sentence. Nowadays, though, HIV-positive people can take daily antiretroviral drugs, which stop the virus from spreading.

“The world of HIV has experienced fantastic success with the development of antiretroviral treatments,” Cabero said. “[People taking these drugs] are not contagious. They have the virus under control and they can have a normal life.”

But one big limitation is that the drugs cannot cure the infection — the virus stays dormant and hidden within immune cells with the potential to rebound if the treatment stops.

In the long term, the drugs end up being the victims of their own success. “Because the treatment is successful, patients are living longer,” Cabero explained. Like everyone else, they start suffering from age-related conditions such as cardiovascular disease and osteoporosis. The problem is that antiretroviral therapy can magnify the effects of these conditions.

Making a vaccine for the infection seems like a step in the right direction for solving this issue, but there are lots of challenges to overcome.

“One of the challenges is that the HIV virus is extremely smart,” Cabero said. “The virus mutates in the replication process very rapidly. If you design a vaccine to target fragments of a virus, or a part that mutates, the vaccine will be ineffective.”

This problem has stalled the production of an HIV vaccine for decades. However, this is changing.

“We’ve seen a revival … of science around the immune response to HIV,” Cabero said. “This has been the basis of some academic groups to make a new attempt to tackle a problem we’ve had for many years that is not yet solved.”

AELIX aims to overcome these limitations by learning from the immune system of people that are innately better at keeping the HIV virus at bay, who are called ‘HIV controllers’. The company analyzed samples from around 1,000 HIV-positive people and found that the immune systems of the controllers target specific regions of the HIV virus that non-controllers’ miss.

Equipped with this knowledge, AELIX has designed an HIV vaccine to convert all patients into controllers, removing the need for daily antiretroviral medication. “We administer the vaccine a number of times, and the aim is to take away the antiretroviral treatment,” Cabero said.

AELIX is currently testing its vaccine in a phase I trial in individuals with early-stage HIV infection, with results expected late 2020. Last year, the company entered a partnership to test its vaccine in combination with Gilead’s drug vesatolimod, which activates HIV viruses hiding in immune cells to make them vulnerable to immunotherapy. Results from the trial are expected by 2021.

AELIX has plenty of competition in designing an HIV vaccine, including a vaccine from the University of Oxford that allowed 5 out of 15 patients to stop antiretroviral therapy for weeks. However, according to Cabero, other teams design vaccines based on target regions using computer predictions, without much practical proof that the regions produce an effective vaccine.

“The major difference of AELIX is that our immunogen is based on real data,” Cabero said. “The inventors have looked at the cells of the infected patients, analyzed which part of the virus is recognized by those cells, and derive the construction of the vaccine in this way. All other vaccines that have been tried are theoretical, in silico.”

Aside from vaccines, there are many different approaches in development to reduce our dependence on antiretroviral therapies. For example, the company TC Biopharm is developing genetically engineered T cell (CAR-T) therapies that could tackle the HIV virus. The company Abivax is developing a drug that can attack the HIV hidden within immune cells, providing a functional cure for the condition.

An alternative approach is using the gene editing tool CRISPR/Cas9, which has entered a storm of controversy after the tool was reportedly used to gene edit babies to express an HIV-resistance mutation, potentially putting their health at risk.

While there are many modern methods for fighting HIV, the field of vaccines is one of the few that has stood the test of time with many other infectious diseases. It’s likely that, whoever crosses the finish line first, vaccines are going to play an important role in HIV treatments to come.

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