After more than 30 years of attempts, there may be a promising advance in the search for a vaccine for HIV, the virus that causes AIDS if left untreated.
Now, preliminary data from an early stage clinical trial out of the International AIDS Vaccine Initiative and The Scripps Research Institute in La Jolla, California, suggests that a new HIV vaccine may hold promise.
"These are very early studies. But nonetheless, they are provocative," said Dr. William Schaffner, a professor of preventative medicine and infectious diseases at Vanderbilt University in Nashville, who was not involved in the clinical trial.
Although the vaccine candidate will still need to be tested in larger studies, experts are hopeful this vaccine might succeed where others have failed.
"This is a very innovative approach to developing a vaccine that hasn't been done before," Schaffner said, who described the underlying vaccine technology as "kind of a culmination of 21st century science."
When HIV was first discovered as the cause for AIDS in the early 1980s, researchers thought that a vaccine for this virus could be created rapidly, as had been done for diseases like measles, chickenpox and hepatitis B. In fact, the then-U.S. secretary of health and human services, Margaret Heckler, predicted in 1984 that a vaccine would be available in two years. Researchers soon found that there were more hurdles than they had initially thought.
HIV is a virus that mutates rapidly, creating a moving target for vaccines. HIV also has many different subtypes, so a vaccine offering protection against one subtype of HIV may be ineffective against another.
The new research out of IAVI and Scripps aims to address these difficulties by developing a vaccine that helps the body create "broadly neutralizing antibodies." The researchers hope to stimulate a person's immune system against many HIV variants and mutations.
This research is based on "identification of a subset of HIV-infected individuals ... who, in the course of their infection, do make so-called broadly neutralizing antibodies, which basically means these antibodies are able to potently block infection of diverse HIV variants, and that is the key goal," said Dr. Mark Feinberg, Ph.D., the CEO of IAVI.
Their early stage, phase 1 clinical trial, which is still underway, involved 48 healthy adults who received a total of two doses of either the vaccine or placebo, two months apart. Preliminary data showed 97% of those who received the vaccine had early evidence that their immune system may be able to make these broad antibodies.
"The broadly neutralizing antibody is important, because the virus can mutate so rapidly that they need something that's a shotgun, not a rifle ... to prevent a whole variety of different kinds of HIV configurations," said Schaffner.
The decadeslong search for an HIV vaccine lies in stark contrast to the development of vaccines for COVID-19, "where the science was ready, and we were able to develop vaccines, plural, very, very quickly," Schaffner added.
The researchers at IAVI and Scripps are collaborating with companies, like Moderna, to harness the mRNA technology used in the development of vaccines against COVID-19.
Sara Yumeen, M.D., is a preliminary-year internal medicine resident at Hartford Healthcare St. Vincent's Medical Center in Connecticut and is a contributor to the ABC News Medical Unit.
The reproductive years for women in the United States may be increasing, according to a new study.
On average, the reproductive years for women increased from age 35 to 37.1, according to the study published Wednesday in the Journal of the American Medical Association.
The age of 35 has for decades been regarded in the medical community as the age when women's reproductive systems slow down and it becomes more difficult to have and sustain a pregnancy. Women who become pregnant at age 35 and above are considered of advanced maternal age and face risks including miscarriage, genetic abnormalities, fetal growth issues, preterm birth, preeclampsia and stillbirth, experts say.
Giving birth later in life is a growing reality in the U.S. though. Since 2007, the birth rate has risen 19% for women in their early 40s, 11% for women in their late 30s and just 2% for women in their early 30s. Birth rates for women in their 20s declined from 2015 to 2016, according to the Centers for Disease Control and Prevention.
The new study that found women's reproductive span now extends to 37 years of reproductive years, on average, looked at 60-year trends in age at natural menopause and reproductive life span and other factors among U.S. women. This increase in reproductive years may be a result of later ages of menopause and earlier ages of first period, on average.
The data showed that average age of menopause for women increased, from 48.4 years to 49.9. And the age that a girl got her first period dropped slightly, on average, from 13.5 years to 12.7.
"These are important numbers," said Dr. Jennifer Ashton, ABC News chief medical correspondent and a board-certified OBGYN. "It's good to get a grip on what's happening over a woman's reproductive life."
The changes in women's reproductive life spans could have potential implications for cases of both heart disease and cancer in women, according to Ashton.
She said the broadening of the life span could mean a slight decrease in cardiovascular disease among women, but could raise the risk of breast cancer, ovarian cancer and endometrial cancer, also known as hormonally responsive cancers.
"The more hormonal stimulation [there is] across a woman's lifetime, those cancers can go up," explained Ashton.
The milestone reproductive moments in women's life spans also come with side effects, which range from mild to severe, according to Ashton.
The side effects can range from fatigue and cramping on the mild end to mood changes, severe pelvic pain and heavy bleeding on the more severe end, according to Ashton. Women may also experience irregular menstrual cycles, changes in sleep patterns, and hot flashes in the years leading up to menopause, which is when women stop having menstrual periods.
"We have to remember these milestones in life, while natural, can be problematic," she said. "There's a range of symptoms."
Three health workers in Norway who had recently received the AstraZeneca COVID-19 vaccine are being treated in hospital for bleeding, blood clots and a low count of blood platelets, Norwegian health authorities said on Saturday.
Norway halted the rollout of the AstraZeneca vaccine on Thursday, following a similar move by Denmark. Iceland later followed suit.
“We do not know if the cases are linked to the vaccine,” Sigurd Hortemo, a senior doctor at the Norwegian Medicines Agency told a news conference held jointly with the Norwegian Institute of Public Health.
All three individuals were under the age of 50.
The European medicine regulator, the European Medicines Agency (EMA,) would investigate the three incidents, Hortemo said.
“They have very unusual symptoms: bleeding, blood clots and a low count of blood platelets,” Steinar Madsen, Medical Director at the Norwegian Medicines Agency told broadcaster NRK.
“They are quite sick...We take this very seriously,” he said, adding that authorities had received notification of the cases on Saturday.
AstraZeneca said an analysis of its safety data covering reported cases from over 17 million vaccine doses given had shown no evidence of an increased risk of pulmonary embolism, deep vein thrombosis or thrombocytopenia - having low levels of platelets.
“In fact, the reported numbers of these types of events for COVID-19 Vaccine AstraZeneca are not greater than the number that would have occurred naturally in the unvaccinated population,” a company spokeswoman said.
Such trends or patterns were also not observed during clinical trials for the vaccine, she added.
Before Denmark and Norway stopped their rollout of the AstraZeneca vaccine, Austria stopped using a batch of the shots while investigating a death from coagulation disorders and an illness from a pulmonary embolism.
The EMA said on Thursday the vaccine’s benefits outweighed its risks and that it could continue to be administered.
Europe is struggling to speed up a vaccine rollout after delivery delays from Pfizer and AstraZeneca, even though new cases have spiked in some countries.
No life is free from pain or suffering. Unfortunately, we will all experience difficult times at one point or another in our lives. While we may not be able to control the things that happen to us, we can control how we react to them. Fostering a sense of resilience is the way to go.
Psychologically defined as “the process of adapting well in the face of adversity, trauma, tragedy, threats or even significant sources of stress,” resilience allows us to be strong through even the most troubling periods. If you’re looking to boost this trait, there are plenty of small changes you can make. Take a look at our expert-backed advice.
Start looking at the bright side“It’s easy to fall into the trap of solely focusing on the negative aspects of a challenging situation; after all, our brains are hardwired to focus on the negative,” says Dr. Sharone Weltfreid, Ph.D., a licensed clinical psychologist. “So, what can we do instead? We can challenge ourselves to consider the upside of our situation. We make the choice to not allow our hardship to define us, overwhelm us, or completely colour our perspective.”
Practising reframing negative experiences daily can lead to low levels of pessimism, according to research published in the Journal of Consulting and Clinical Psychology. Whenever you experience something negative, take a moment to stop and notice the positive side of it. Slowly but surely, this habit will become a reflex.
Avoid catastrophizing situations“Catastrophizing is a cognitive distortion (i.e. faulty thinking) in which we predict the worst possible outcome for our situation and exaggerate its impact. For example, if you make a minor mistake at work, you may be convinced your boss will fire you.”
“Naming our experience allows us to gain distance from it and take perspective. We can then ask ourselves, ‘What is the likelihood of the worst-case scenario happening?’, ‘What is the best-case scenario?’, and ‘What is the most realistic scenario?’ You can also consider if there are any actions you can take to improve the situation,” explains Dr. Weltfreid.
Invest in your future selfThings may feel unstable right now. However, investing in yourself could help assure a happy and bright future. “When you are uncertain about what the future may hold, by investing in your future you can offer yourself some assurances,” says Dr. Christopher Ryan Jones, Psy.D., host of the Sex Therapy with Dr. Jones podcast.
“This could be learning a new skill, going back to college, investing money, or any number of things that are important to you. This way, regardless of what happens in the future, you are assured that one area of your life is taken care of.”
Savour everyday joys“Even in the midst of hardship, we can always find pleasure in everyday joys. When you identify something positive during your day, like taking a warm shower or receiving kind words from a friend, take the time to really revel in the positive feelings associated with the event,” says Dr. Weltfreid.
If you need a prompt to get you started, there’s a daily habit you can try. “One activity that can help you to savour the good in your everyday life is to write down 3-5 experiences of happiness at the end of each day. Knowing that you will be writing about your positive experiences can help you to scan your environment to find events that bring you joy.”
Get more sleep each nightWhen you’re feeling overwhelmed by worries, getting your 40 winks can be difficult. However, it’s in difficult times that quality sleep is most important. Research published by the American Psychological Association suggests that more sleep would make most people happier and healthier, while sleep deprivation has the opposite effect.
“When we sleep well, we boost our immunity, regulate our moods, heighten our brain functioning, and decrease our stress,” says Dr. Weltfreid. “To maximize our chances to get good sleep, we need to do what we can to ensure that our circadian rhythm stays balanced.”
Suggestions to do that include: “maintaining a consistent sleep schedule, having a sleep space that is dark and cool, avoiding bright lights, limiting caffeine intake in the afternoon, exercising in the early morning or afternoon, and getting morning sunlight for about 30 minutes. You also want to engage in activities before bed that help you wind down and relax such as meditation, a warm bath, and reading.”
Take pride in overcoming challengesNeedless to say, 2020 has presented all of us with challenges. When you’re trying to overcome the obstacles ahead of you, it’s hard to see the bigger picture. However, try to reframe this challenge as an essential task, and take pride in how you are managing it.
“There is a saying that today's troubles are tomorrow's testimonies,” says Dr. Jones. “By remembering that you have overcome hardships and adversity in the past, you can remind yourself of your resilience and ability to overcome things that may come in the future.”
Get in touch with natureIf you’re feeling overwhelmed by the strains of the modern world, take a break in the great outdoors. “Though nature has a way of capturing our attention and bringing us to the present, we can increase our connection to it via mindfulness,” says Dr. Weltfreid. “Try to immerse yourself fully in nature by engaging all of your senses.”
“Notice how the wind feels on your face, listen to the birds chirping, [and] observe the beauty and uniqueness of each tree. When we intentionally focus our attention on the beauty and wonder of nature, we allow ourselves the opportunity to get outside of ruminative or worrisome thoughts and experience joy, curiosity, connection, and gratitude.”
Use positive affirmationsIf you’re looking to boost your self-esteem and resilience, using positive affirmations could be the answer. You may want to write down positive statements that fill you with strength and leave them in visible places around your home. On the other hand, some people find that it is helpful to repeat affirmations to themselves as you might a mantra.
If you’re stuck in a negative thought cycle, you can even try using affirmations to change your mindset for the better. “This is a great way to combat negative thoughts,” says Dr. Jones. “Whenever a negative thought enters your mind, by offering a positive thought in its place you can combat being overwhelmed by negativity.”
Engage in mindful breathingHow you breathe can have a remarkable impact on your emotional well-being. “One of the foundational mindfulness meditations involves focusing your attention on your breath; appropriately, it’s called ‘mindfulness of breathing’,” explains Dr. Weltfreid.
“Find a comfortable position and close your eyes, or if it’s more comfortable, soften your gaze. Next, experience the sensation of your in-breath and out-breath without attempting to change it. When you notice that your mind has wandered, which is completely normal, gently redirect your attention to your breath—your anchor to the present moment. Continue redirecting your attention to your breathing each time you are distracted.”
Dr. Weltfreid also suggests using popular apps, such as Headspace or Calm, as well as guided meditations on YouTube, such as the ones by The Honest Guys.
Focus on physical exerciseWhile you may be feeling lethargic and unmotivated, engaging in physical exercise could be one of the best ways to boost your resilience. Not only does this activity give you something to focus on, but it will also improve your physical and emotional wellness.
“There are so many benefits to exercise, both physically and mentally,” says Dr. Jones. “Besides the hormonal releases inside of the body, the time spent running or participating in activities allows you to clear your mind and refocus on important things in your life.”
Try to be present in the momentMindfulness doesn’t have to be hard. “You can practise mindfulness informally by exercising non-judgmental present moment awareness during your everyday activities such as eating, listening to someone, or walking,” says Dr. Weltfreid.
“As you mindfully approach each activity, try to engage as many of your senses as possible. If you take a walk, try to view the details of your surroundings. When your mind wanders, gently bring it back to your surroundings. Know that you will feel less anxious and more centred, the more that you can keep your attention on the present moment.”
Speak to the people around youSometimes, all you need is a little help from your friends. “Resilient people rely on social support to help them through difficult times,” explains Dr. Weltfreid.
“Seek support from people who are empathic and understanding. If you do not currently have such people in your life, consider reaching out to people from your past, trying to befriend a co-worker or neighbour, or thinking creatively about developing connections. Speaking to people at this time can help you to feel less alone and isolated.”
Offer support to other peopleOne way to boost your resilience through difficult times is to offer support to those around you. In doing so, you can strengthen your social connections and experience the satisfaction of being able to help others through this period.
“We are social creatures and as such need to stay connected to each other. Reach out to people to check in with them about how they are doing,” says Dr. Weltfreid. “Be a good listener and offer your understanding and support. You can also try to make new connections by joining an outdoor exercise class or an online book club.”
Avoid compounding your problems“There are situations in life that are unavoidable. Dealing with them is difficult enough as it is. However, for some people, when they are exceptionally stressed, anxious, or nervous, they look for other situations that are not healthy to be a part of. I call this the ‘nuclear option,’” says Dr. Jones.
“It’s like they want to blow up everything in their life at once. I recommend, when people feel this way, to avoid [negative] situations and people who encourage these situations until you are clear-headed and capable of making positive and meaningful decisions.”
Remember that this won’t last foreverNothing is permanent. If you’re facing tough times, you may find it hard to believe that they will ever come to an end. However, you can use the knowledge that they will to embolden you and make you feel stronger through a difficult period.
“When we are suffering, it can be difficult to imagine that we will ever be free of suffering. We can counter our tendency to project our current suffering into the future by reminding ourselves of the popular adage, ‘this too shall pass’. Believing that there is a light at the end of the tunnel can help us persevere during these challenging times,” says Dr. Weltfreid.
Avoid ruminating on negative thoughtsAre you caught up in a vicious cycle? When your mindset is negative, your outlook will be too. “When we ruminate, we continuously replay the same negative thoughts about an upsetting situation,” explains Dr. Weltfreid. “We may repeatedly beat ourselves up for a mistake we made and consider all of the alternative ways we could have behaved.”
“Rumination keeps us living in our minds and prevents us from moving forward. It is a pathway to depression and anxiety and inhibits our ability to think more broadly. We can break out of this negative neural network by shifting our attention to a pleasant activity. For example, we can read a book, speak to friends or family, or listen to music.”
Practise self-loveDo you find yourself looking for validation from others? It’s time to stop. “Self-love is the foundation upon which we can create a happy and fulfilling life,” says Dr. Weltfreid. “When we love our true selves, we do not need external validation that we are worthy.”
“By not making our worth contingent on external factors, we experience more stable self-esteem. We live by our values and engage in the world from our core strengths. We also seek meaningful connections with people who have our best interest in mind.”
Enhance your self-care practiceThere has never been a more important time to practise self-care. Looking out for your baseline needs and ensuring you are happy and healthy could boost your resilience. The good news is that you can incorporate this practice into your daily routine.
There’s a lot of misinformation surrounding self-care, but it doesn’t have to be difficult to get started. Keep things simple. “Self-care practices include exercising, eating well, sleeping well, etc.,” says Dr. Weltfreid. “When we nourish our body, mind, and spirit, we send the message to ourselves that we are of value.”
Learn the art of forgivenessAre you holding grudges against people? When things get difficult, we often look for someone to blame. Engaging in forgiveness could lead to long-term happiness, according to research from the University of Leicester. This change may also help you become more resilient.
“I am a big advocate for forgiveness,” says Dr. Jones. “Failure to [forgive] often leads to bitterness and resentment. As a Jewish practitioner, I strongly believe in showing kindness to others. I believe that by doing acts of kindness, we bring joy into our own lives.”
Learn some self-compassionThe story you tell yourself dictates how you feel. If you’re constantly telling yourself that you’re not good enough or that you can’t cope, you will start to believe that narrative. Switch things up and speak to yourself as you would a good friend. By doing so, you can learn to practise self-compassion and give yourself some needed support.
“We also build self-love by offering ourselves self-compassion versus criticism when we are facing difficulties,” says Dr. Weltfreid. “For example, when we are facing challenges, we can provide reassuring words to ourselves, e.g. ‘It's okay, everyone makes mistakes’.”
Source: Expresso Communication
When Pfizer and BioNTech announced their astounding SARS-CoV-2 vaccine efficacy results in November, Arthur Reed was ecstatic.
“The global investment and coordination of billions of dollars enabling this unprecedented pace of scientific discovery is truly an incredible achievement,” he said.
But as a gay man in New York City living with HIV since the 1980s, he couldn’t help but wonder about the government and public response to SARS-CoV-2, the virus that causes COVID-19, compared to the early days of HIV/AIDS.
“Unfortunately, in both cases there has been immense stigma against minority communities,” Reed said. “Calling COVID-19 the ‘Chinese Virus,’ and the ensuing rise in anti-Asian scapegoating, feels eerily similar to when people labeled HIV as ‘gay-related immune deficiency’ and shunned us from society.”
What Reed finds especially triggering are the COVID-19 hospital policies that don’t allow visitors, and the patients having to die alone in isolated hospital beds. Media images of FaceTime farewells and sparsely populated funerals painfully remind him of an earlier decade, when patients with HIV/AIDS — many of whom were his closest friends — also died alone. This happened not only because of hospital policies, but because of discriminatory social dynamics and a vicious lack of acknowledgement of the deadly disease at the uppermost rungs of the federal government.
“I lost over 100 friends in the early days of HIV. And it was awful, because these people were like my family,” he said. “The worst part of it all was that it also took my partner’s life.”
The deep and reverberant trauma from these losses and his own fight against the virus have motivated him to keep up with the latest research on HIV. And while he has nothing but awe and praise for the scientists working on these viruses, he cannot help but wonder how a vaccine against SARS-CoV-2 was developed in less than a year — especially since developing new vaccines is a process that typically takes eight to 10 years — while there’s been nothing on the horizon for HIV in nearly four decades.
Reed’s not the only one wondering about this. On World AIDS Day, observed annually on Dec. 1 ― which this year fell only a few weeks after Pfizer’s announcement ― commenters on Twitter amplified the differences between SARS-CoV-2 and HIV vaccine development. Many offered conspiratorial “explanations” for the lack of an HIV vaccine.
Some theorized that the sole reason for this discrepancy is that HIV mostly affects trans people of color and men who have sex with men — marginalized groups without much political clout. Since SARS-CoV-2 is affecting all levels of society (even though the ultimate health outcomes are worse for ethnic minorities), they believe it has garnered quicker attention and unprecedented monetary investment, leading to a (thus far) successful vaccine.
Other commenters have falsely claimed that HIV is “money-making” for governments and pharmaceutical companies alike, and so vaccines have been strategically withheld.
It’s always hard to argue against more funding, since every step of the scientific discovery process is extremely resource-intensive. But it is worth noting that since 1982, federal funding for HIV has increased exponentially, to nearly $35 billion in 2019 alone. Additionally, private funders like the Bill & Melinda Gates Foundation have provided critical financial support over the decades.
To put this in the financial context of Operation Warp Speed ― a public-private partnership initiated by the United States government to facilitate SARS-CoV-2 vaccine discovery, therapeutics and diagnostics ― nearly $18 billion has been budgeted for the project.
“At the moment, I don’t think funding is necessarily the biggest bottleneck to an HIV vaccine breakthrough, although more funding never hurts,” said John Moore, a professor of microbiology and immunology at Weill Cornell Medicine in New York City who has been studying HIV vaccine development for over 20 years.
“At the end of the day, it’s the fundamental differences in the biology of HIV and SARS-CoV-2 that make developing a vaccine so difficult — not for a lack of trying,” Moore said. He dismissed the conspiracy theories as “absurd.”
“Some of these conspiracy theories have unfortunately been around for a while,” said Gregg Gonsalves, an assistant professor of epidemiology at the Yale School of Public Health and a renowned HIV activist. “Now more than ever, we have to continue meeting people where they’re at and identify trusted messengers within communities to dispel these myths.”
Why making a COVID-19 vaccine was faster
While it feels intuitive to compare the two viruses, there are only a few molecular-level similarities. The most prominent is that they both have “spike” proteins ― knob-like structures jutting out of their surfaces (though the structures on the two viruses differ in composition).
Both viruses use these spike proteins to bind to receptors, which are molecules that sit on the surfaces of human cells. In the case of SARS-CoV-2, the virus binds to cells with the ACE2 receptor found in the lungs, small intestine, blood vessels and many other parts of the body — which is why it is not surprising that COVID-19 affects so many different organs. HIV, however, binds to different receptors of immune system cells.
After entry into the cell, the two viruses do very different things. SARS-CoV-2 makes numerous copies of itself, which allows it to go on to infect more cells in the body.
HIV, on the other hand, has a much more sophisticated replication process. One of the most notable differences is that HIV particles have a way to replicate the virus’ genetic material so it becomes integrated into the human cell’s DNA. SARS-CoV-2 cannot emulate this mechanism.
So what does all of this mean for vaccines? What makes it so difficult to produce one for HIV?
“Among a whole host of factors, HIV has an extremely high mutation rate that impacts the architecture of the spike protein antibody recognition sites. And these mutations can happen daily, which is a significant challenge to HIV vaccine development,” Moore said. “On the other hand, the SARS-CoV-2 spike protein has been fairly static up until recently.” This gave scientists a chance to develop an effective vaccine, since that spike protein wasn’t changing too much.
SARS-CoV-2 mutants are now gaining traction. But there is little evidence so far to suggest that the currently available vaccines will be ineffective against these mutant strains. However, Moore said, “we cannot completely rule out the possibility of having to tweak the vaccines in the future to account for these mutations.”
Another critical difference between the two viruses is the topography of the receptor binding domains — areas on the spike proteins that, if strategically hindered by antibodies, can prevent the virus from attaching to its host cell altogether.
“In SARS-CoV-2, this region sticks out like a sore thumb, which makes it relatively targetable by antibodies,” Moore said. “But in HIV, the site is not only buried but also heavily coated with sugars.” This makes it difficult to prevent a fusion to a cell.
But decades of tedious HIV vaccine research have not been entirely futile.
“It is important that people — especially those spewing conspiracy theories —realize that a lot of the things we learned from years of grueling HIV research have paved the way to formulate vaccines and therapeutics against SARS-CoV-2,” said Kenneth Mayer, the medical research director and co-chair of the Fenway Institute in Boston and a professor in the department of global health and population at Harvard T.H. Chan School of Public Health.
As one example, the Moderna and Pfizer/BioNTech vaccines both deliver the SARS-CoV-2 spike protein through messenger RNA (or mRNA) technology. Immune cells sense the spike proteins and produce a huge reservoir of antibodies in response. If a vaccinated person comes in contact with the virus, they start making antibodies. Along with already-primed white blood cells, these antibodies kick in, neutralize the virus and prevent it from infecting a cell.
This approach originally emerged from better understanding the surface proteins of HIV and engineering antigens to elicit an immune response. But so far, this approach has been unsuccessful for HIV because of its high genetic diversity and rates of mutation.
As another example, the University of Oxford/AstraZeneca vaccine uses a weakened common-cold adenovirus to introduce the SARS-CoV-2 spike protein to generate antibodies. (Note: This isn’t the coronavirus that causes COVID-19, and it won’t make the recipient sick with the disease.)
“Again, this approach stems from HIV vaccine trials from the early 2000s, where weakened adenoviruses were used to deliver genes found in HIV,” Mayer said. While those initial trials yielded disappointing results, fine-tuning the underlying principle has led to successes with numerous other viruses, including SARS-CoV-2.
It is worth noting that the HIV research community hasn’t completely walked away from using these adenoviruses to advance trials. In fact, the same adenovirus currently being studied in a large Janssen HIV vaccine trial is also being used in their COVID-19 vaccine trial.
What’s next for HIV vaccine research
While the long-term effectiveness of vaccines against SARS-CoV-2 will continue to be monitored — especially in light of the new mutant strains — there are several ongoing and future directions for HIV vaccine development.
“Currently, one of the more promising avenues is the use of broadly neutralizing antibodies,” or bNabs, said Douglas Nixon, a professor of immunology in medicine at Weill Cornell Medicine.
These are specialized proteins that can bind to and neutralize a wide range of HIV subtypes, as opposed to non-broadly neutralizing antibodies, which can only nullify one strain of the virus. From studying individuals who seem to have an innate resistance to HIV infection, researchers can continue to identify how these bNabs are generated and, hopefully, test them out in clinical trials.
Another approach that scientists are working on is known as “kick-kill.” While there is still a lot more to learn, the idea here is to use one set of compounds that can “kick” HIV from its dormant state in cells, and another set to kill the freely circulating viruses.
Also, a question that’s on everyone’s mind is whether an mRNA vaccine, similar to what’s being used for SARS-CoV-2, will work for HIV. While there are no human trials yet, Moderna does have an ongoing investigation in monkeys, and the results have inspired cautious optimism. If the data continues to look promising, then human trials could well be on the horizon.
“But beyond the science alone, there are some critical ethical considerations when it comes to designing HIV vaccine trials,” Mayer said. “Since we still don’t know of any [preventative] medication for SARS-CoV-2, it’s easier to have a placebo arm. But that’s not the case for HIV, because we have medications like Truvada and Descovy that can be taken as pre-exposure prophylaxis that effectively stop the transmission of HIV.”
As a result, when recruiting people for HIV vaccine trials, the inclusion criteria get very tricky, which adds more time to the design and implementation of studies.
The other big barrier involves attracting talent to the U.S., given the “myopic immigration policies” of the past four years, Moore said. “Many of us investigators are having to deal with these consequences in our own labs, and having to figure out ways to recruit and retain these highly talented people.”
But with hopes of more inclusive immigration policies under the Biden administration ― and continued financial and scientific investments in HIV research ― great strides can be made in advancing this field.
“A huge collaborative momentum has already begun with Operation Warp Speed,” Nixon said. “Let’s keep it going with ‘Operation Warp Speed for HIV Too,’ or Operation HIVVAX, or Operation Hyperdrive, whatever you want to call it.”
The UK's National Health Service (NHS) is to pilot a simple blood test that may detect more than 50 types of cancer and, it is hoped, could help thousands of people by allowing the disease to be treated more successfully at an earlier stage.
The Galleri blood test, developed by Californian healthcare company Grail, will be piloted with 165,000 patients in what the NHS described as a "world-first deal" in a news release Friday.
Grail, whose work is focused on detecting cancer early, is backed by investors including tech billionaire Bill Gates and Amazon founder Jeff Bezos.
NHS England hopes the blood test will be particularly useful in identifying types of cancer that are currently difficult to diagnose and treat early.
"Early detection -- particularly for hard-to-treat conditions like ovarian and pancreatic cancer -- has the potential to save many lives," said NHS chief executive Simon Stevens.
More than 1,000 people are newly diagnosed with cancer every day in the UK, he added.
The pilot program, due to start in mid-2021, will involve 165,000 people, including 140,000 aged from 50 to 79 who have no symptoms but will have annual blood tests over three years.
The remaining 25,000 participants will be people with possible cancer symptoms who will be offered the blood test to speed up their diagnosis after they are referred to hospital in the normal way, the news release said.
Results are expected by 2023, after which it is hoped one million people could receive the test by 2025, expanding this to the wider population thereafter, NHS England said.
In England, around half of cancers are currently diagnosed at stage one or two but the NHS aims to increase that to three quarters by 2028, the news release said.
Grail said in a press release that according to modeling data, "adding Galleri to existing standard of care has the potential to decrease the number of cancers diagnosed at late stage by nearly half, which could reduce the total number of cancer deaths in the UK by approximately one-fifth."
Five-year relative survival for cancer in the UK is below the European average, according to charity Cancer Research UK.
Lawrence Young, professor of Molecular Oncology at the University of Warwick, said the Galleri test was one of a number of novel blood tests being developed to detect cancer at a very early stage when it is more easily treated.
"There are a number of trials evaluating this approach and a publication from the Circulating Cell-free Genome Atlas (CCGA) consortium examining the Galleri test in 6,689 participants has generated very encouraging results in more than 50 different cancers at different stages of development," he told the Science Media Centre.
However, not all cancer experts agree that the NHS should be piloting the Galleri blood test.
Paul Pharoah, professor of Cancer Epidemiology at the University of Cambridge, told the Science Media Centre he had doubts about the scientific basis for the pilot based on the limited published research available.
"The Galleri blood test is a test that might be able to detect cancer in the blood in individuals with early cancer, though the evidence that it does this effectively is weak," he said. "The NHS should not be investing in such a test before it has been adequately evaluated in well-conducted, large-scale clinical trials."
Michelle Mitchell, Cancer Research UK's chief executive, said tests such as that developed by Grail had "great transformative potential" if they prove effective in detecting cancer earlier.
Dr. Jodie Moffat, head of early diagnosis at Cancer Research UK, said results so far from studies outside the UK had been promising. "But the sample sizes, particularly for some cancer types, have been very small and so it needs to be tested in a much larger sample, and with longer follow up of patients not testing positive with the blood test to understand where it is missing cancers," she told the Science Media Centre.
"Based on the evidence we have seen, the test is not currently that good at picking up stage I cancer, where it is small and hasn't spread to other parts of the body."
Source: CNN Health
Italy on Sunday ordered bars and restaurants to close by 6 p.m. and shut public gyms, cinemas and swimming pools to try to halt a rapid resurgence in the coronavirus that has pushed daily infection rates to new records.
The measures, which take effect on Monday and were agreed between Prime Minister Giuseppe Conte’s government in Rome and regional authorities, arrived after two nights of protests in Naples and Rome against curfews introduced in a number of regions last week.
Aware of the huge cost of shutting down the economy, the Rome government has said it does not want to repeat the blanket lockdown ordered in the first phase of the crisis. But it has been forced to ratchet up restrictions steadily as the pandemic has raced ahead after slowing down in the summer.
The decree encourages people not to go out and to limit contacts at home with anyone outside their immediate family, but does not impose a mandatory nationwide curfew or lockdown and allows shops and most businesses to remain open.
However, service in bars and restaurants will be subject to a series of controls to limit contagion, and cinemas, theatres, gaming halls and disotheques will be closed.
The decree also directs that up to three quarters of high school teaching should be done online to limit the number of pupils in school buildings.
Italy, once the country hardest hit by the pandemic in the industrialised world, has been overtaken by others in Europe including Spain, France and Britain, but case rates have been rebounding rapidly and health services have come under increasing pressure.
On Saturday, authorities reported a new record daily total of 19,644 infections, as well as 151 deaths from the respiratory disease.
The protests in Naples and Rome, while limited in scale, underlined the tense political climate facing Conte’s coalition government between the anti-establishment 5 Star Movement and the centre-left Democratic Party.
Conte was generally praised for his handling of the initial phase of the crisis but has come under increasing fire for failing to strengthen preparations including testing and contact tracing over the summer.
Certain oral antiseptics and mouthwashes may have the ability to inactivate human coronaviruses, according to a Penn State College of Medicine research study. The results indicate that some of these products might be useful for reducing the viral load, or amount of virus, in the mouth after infection and may help to reduce the spread of SARS-CoV-2, the coronavirus that causes COVID-19.
Craig Meyers, distinguished professor of microbiology and immunology and obstetrics and gynecology, led a group of physicians and scientists who tested several oral and nasopharyngeal rinses in a laboratory setting for their ability to inactivate human coronaviruses, which are similar in structure to SARS-CoV-2. The products evaluated include a 1% solution of baby shampoo, a neti pot, peroxide sore-mouth cleansers, and mouthwashes.
The researchers found that several of the nasal and oral rinses had a strong ability to neutralize human coronavirus, which suggests that these products may have the potential to reduce the amount of virus spread by people who are COVID-19-positive.
“While we wait for a vaccine to be developed, methods to reduce transmission are needed,” Meyers said. “The products we tested are readily available and often already part of people’s daily routines.”
Meyers and colleagues used a test to replicate the interaction of the virus in the nasal and oral cavities with the rinses and mouthwashes. Nasal and oral cavities are major points of entry and transmission for human coronaviruses. They treated solutions containing a strain of human coronavirus, which served as a readily available and genetically similar alternative for SARS-CoV-2, with the baby shampoo solutions, various peroxide antiseptic rinses and various brands of mouthwash. They allowed the solutions to interact with the virus for 30 seconds, one minute and two minutes, before diluting the solutions to prevent further virus inactivation. According to Meyers, the outer envelopes of the human coronavirus tested and SARS-CoV-2 are genetically similar so the research team hypothesizes that a similar amount of SARS-CoV-2 may be inactivated upon exposure to the solution.
To measure how much virus was inactivated, the researchers placed the diluted solutions in contact with cultured human cells. They counted how many cells remained alive after a few days of exposure to the viral solution and used that number to calculate the amount of human coronavirus that was inactivated as a result of exposure to the mouthwash or oral rinse that was tested. The results were published in the Journal of Medical Virology.
The 1% baby shampoo solution, which is often used by head and neck doctors to rinse the sinuses, inactivated greater than 99.9% of human coronavirus after a two-minute contact time. Several of the mouthwash and gargle products also were effective at inactivating the infectious virus. Many inactivated greater than 99.9% of virus after only 30 seconds of contact time and some inactivated 99.99% of the virus after 30 seconds.
According to Meyers, the results with mouthwashes are promising and add to the findings of a study showing that certain types of oral rinses could inactivate SARS-CoV-2 in similar experimental conditions. In addition to evaluating the solutions at longer contact times, they studied over-the-counter products and nasal rinses that were not evaluated in the other study. Meyers said the next step to expand upon these results is to design and conduct clinical trials that evaluate whether products like mouthwashes can effectively reduce viral load in COVID-19-positive patients.
“People who test positive for COVID-19 and return home to quarantine may possibly transmit the virus to those they live with,” said Meyers, a researcher at Penn State Cancer Institute. “Certain professions including dentists and other health care workers are at a constant risk of exposure. Clinical trials are needed to determine if these products can reduce the amount of virus COVID-positive patients or those with high-risk occupations may spread while talking, coughing or sneezing. Even if the use of these solutions could reduce transmission by 50%, it would have a major impact.”
Future studies may include a continued investigation of products that inactive human coronaviruses and what specific ingredients in the solutions tested inactivate the virus.
Janice Milici, Samina Alam, David Quillen, David Goldenberg and Rena Kass of Penn State College of Medicine and Richard Robison of Brigham Young University also contributed to this research.
The research was supported by funds from Penn State Huck Institutes for the Life Sciences. The researchers declare no conflict of interest.
Hospitalized coronavirus patients who took daily aspirin for cardiovascular health had a lower death risk than those who did not take aspirin, according to the findings of a new study conducted by researchers with the University of Maryland School of Medicine.
Patients who took aspirin also had a lower risk of complications, while their chances of requiring admission into the hospital’s intensive care unit (ICU) and being ventilated also fell, according to a news release regarding the findings, which were published Wednesday in the journal Anesthesia and Analgesia.
For the study, the team looked at the medical records of some 412 patients who were hospitalized due to complications with COVID-19. The average age of patients was 55. All patients in the study were treated at the University of Maryland Medical Center in Baltimore or three other hospitals along the East Coast, per the release. Any of the patients’ preexisting conditions, such as hypertension, diabetes, kidney disease, and others, as well as age, gender, body mass index and race, were all accounted for in the study.
Roughly a quarter of the patients were taking daily, low-dose aspirin before they were admitted or began taking the drug shortly after they were admitted to the hospital.
Following their analysis, the study authors concluded that those who took aspirin had a 44% reduced chance of requiring ventilation, and a 43% less risk of requiring admission into the ICU. Most importantly, the researchers said, those who took aspirin also had a 47% reduced risk of dying in the hospital compared to those who did not take the drug.
“The patients in the aspirin group did not experience a significant increase in adverse events such as major bleeding while hospitalized,” they added. (Daily use of low-dose aspirin, which is often recommended for those who have previously suffered a heart attack or stroke to prevent future blood clots, can increase the risk “of major bleeding or peptic ulcer disease,” the researchers explained.)
The researchers hypothesize that aspirin’s blood-thinning effects may have played a role in the positive outcomes for hospitalized patients taking the drug, as COVID-19 infections “increase the risk of dangerous blood clots that can form in the heart, lungs, blood vessels and other organs. Complications from blood clots can, in rare cases, cause heart attacks, strokes and multiple organ failure as well as death,” they said.
“This is a critical finding that needs to be confirmed through a randomized clinical trial,” said study leader Dr. Jonathan Chow, an assistant professor of anesthesiology at the University of Maryland School of Medicine, in a statement. “If our finding is confirmed, it would make aspirin the first widely available, over-the-counter medication to reduce mortality in COVID-19 patients.”
The researchers in the study also noted that the findings provide “cautious optimism,” but warned any COVID-19 patients should speak with their doctor before taking daily aspirin, as those who suffer from chronic kidney disease or use other medications such as blood thinners may not be able to take the drug.
“While confirmatory studies are needed to prove that aspirin use leads to better outcomes in COVID-19, the evidence thus far suggests that patients may want to discuss with their doctor whether it is safe for them to take aspirin to manage potentially prevent serious complications,” said the Dr. E. Albert Reece, the executive vice president for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers distinguished professor and dean at the University of Maryland School of Medicine, in a statement.
A second pathway into cells for SARS-CoV-2: New understanding of the neuropilin-1 protein could speed vaccine research
When it comes to how the coronavirus invades a cell, it takes three to tango. The dance began with the ACE2 receptor, a protein on human cells that allows SARS-CoV-2, the virus that causes COVID-19, to enter and infect the cell. But now enter a new dance partner – another protein – that is present on human cells. This tango of three proteins – two human and one viral – enhances the ability of SARS-CoV-2 to enter human cells, replicate and cause disease.
COVID-19 has crippled health care systems and economies worldwide. Extraordinary efforts are underway to develop vaccines and other therapies to combat this virus. But for these efforts to succeed, understanding how the virus enters cells is critical. To that end, in two papers published in Science, two teams independently discovered that a protein called the neuropilin-1 receptor is an alternative doorway for SARS-CoV-2 to enter and infect human cells. This is a major breakthrough and a surprise, because scientists thought neuropilin-1 played roles in helping neurons make the correct connections and aiding the growth of blood vessels. Before this new research, no one suspected that neuropilin-1 could be a door for SARS-CoV-2 to enter the nervous system.
My colleagues and I were particularly intrigued by these reports because as neuroscientists who study how pain signals are triggered and transmitted to the brain, we were also probing the activity of neuropilin-1. In a recent paper our team showed how neuropilin-1 is involved with pain signals and how, when the SARS-CoV-2 virus attaches to it, it blocks pain transmission and relieves pain. The new work shows that neuropilin-1 is an independent doorway for the COVID-19 virus to infect cells. This discovery provides insights that may reveal ways to block the virus.
Neuropilin-1 helps SARS-CoV-2 get in
A protein called Spike that sits on the outer surface of SARS-CoV-2 allows this virus to attach to protein receptors of human cells. Recognizing that a tiny piece of Spike was similar to regions of human protein sequences known to bind to neuropilin receptors, both research teams realized that neuropilin-1 may be critical for infecting cells.
Using a technique called X-ray crystallography, which allows researchers to see the three-dimensional structure of the Spike protein at a resolution of individual atoms, as well as other biochemical approaches, James L. Daly of the University of Bristol and colleagues showed that this short sequence from Spike attached to neuropilin-1.
In experiments in the lab, the SARS-CoV-2 virus was able to infect fewer human cells that lacked neuropilin-1.
In cells with both the ACE2 and neuropilin-1 proteins, SARS-CoV-2 infection was greater compared to cells with either “doorway” alone.
Daly and colleagues showed that SARS-CoV-2 was able to infect fewer cells if they used a small molecule called EG00229 or antibodies to block the Spike protein’s access to neuropilin-1.
Neuropilin-1 receptor helps virus infect cells.
Using similar methods, a team led by German and Finnish researchers came to the same conclusions as the first study. Specifically, this team showed that neuropilin-1 was critical for the SARS-CoV-2 virus to enter and infect cells.
By using an antibody to block one region of the neuropilin-1 receptor protein, the researchers showed that SARS-CoV-2 harvested from COVID-19 patients could not infect cells.
In another experiment, Ludovico Cantuti-Castelvetri of the Technical University Munich and colleagues attached silver particles to synthetic Spike proteins made in the lab and found that these particles were able to enter cells that carried neuropilin-1 on their surfaces. When they did the same experiments in live mice, they found that the silver particles entered cells lining the nose. The researchers were surprised to discover the Spike protein could also enter neurons and blood vessels within the brain.
Neuropilin-1 receptor helps virus infect cellsUsing tissues from human autopsies, Cantuti-Castelvetri and colleagues noted that neuropilin-1 was present in the cells lining the human respiratory and nasal passages, while the ACE2 protein was not. This demonstrates that neuropilin-1 provides an independent doorway for the COVID-19 virus to infect the cells.
Moreover, cells lining the nasal passages from COVID-19 patients that were positive for neuropilin-1 were also positive for the Spike protein. These findings confirmed that Spike uses the neuropilin-1 protein to infect human cells in regions of the body where ACE2 isn’t present.
Neuropilin-1 can block viruses, cancer and pain
In a surprising discovery recently reported by our lab, we found that the SARS-CoV-2 Spike protein has a pain-relieving effect. Even more surprising was the finding that this analgesia involved the neuropilin 1 receptor.
We demonstrated that Spike prevented a protein from binding to neuropilin-1, which blocked pain signals and brought pain relief. That is because when this protein, called Vascular Endothelial Growth Factor A (VEGF-A) – which is produced by many cells in the body – binds to neuropilin-1 under normal circumstances, it initiates the process of pain signaling by exciting neurons that convey pain messages.
So, the virus revealed to us a potential new target – the neuropilin-1 receptor – for managing chronic pain. Now if we can decipher how neuropilin-1 contributes to pain signaling, then we be able to target it to design ways to block pain.
In our lab, we are now taking advantage of how Spike engages neuropilin-1 to design new pain inhibitors. In this report on the preprint server BioRxiv, we have identified a series of novel compounds that bind to neuropilin-1 in a manner that mimics Spike. These molecules have the potential to interfere with neuropilin-1 function including SARS-CoV-2 virus entry, and block pain signals and even cancer growth.
More dance partners to come
The studies by Daly and colleagues and Cantuti-Castelvetri and colleagues shift our collective focus onto neuropilin-1 as a potential new target for COVID-19 therapies.
These studies also have implications for the development of vaccines against the Spike protein. Perhaps the most important implication is that the neuropilin-1 binding region of Spike should be targeted for COVID-19 prevention. Because a number of other human viruses, including Ebola, HIV-1 and highly virulent strains of avian influenza, also share this signature sequence of Spike, neuropilin-1 may be a promiscuous mediator of viral entry.
But it appears that the tango is not over yet. More dance partners have emerged. PIKFyve kinase and CD147 – two proteins – have also been shown to bind Spike and facilitate viral entry. Whether these new partners take center stage or play second fiddle to ACE2 and neuropilin-1 remains to be seen.
Source: The Conversation