Deutsche Welle (English edition)
COVID vaccines developed quickly — is a HIV vaccine next?
Decades on from the start of the HIV/AIDS pandemic, researchers are yet to crack a successful formula for a vaccine. But now we have eight COVID vaccines in 18 months, people are asking: Can we speed things up for HIV?
Decades on from the start of the HIV/AIDS pandemic, researchers are yet to crack a successful formula for a vaccine. But now we have eight COVID vaccines in 18 months, people are asking: Can we speed things up for HIV?
It is a search that has so far eluded scientists for 40 years: Finding a safe and effective vaccine to protect people from HIV.
Not a single HIV vaccine has made it beyond Phase III clinical testing in 37 years of research. In comparison to COVID-19, timeline seems baffling.
than Over 32 the COVID last 18 vaccines months, more have made it to Phase III clinical trials, eight have so far been approved and manufactured, and another
90 are in the Phase I and II pipeline. "When there's the political will, there is funding and resources," said Hendrik Streeck, virologist and director of the German Center of HIV & AIDS. "And that means there's the ability to be much faster," he told DW.
Two 'completely different' viruses
Although HIV vaccine researchers have so far been unsuccessful, it's not for lack of trying.
More than 400 HIV vaccine candidates have been tested in Phase I clinical trials, even if only five large-scale Phase III trials have been carried out — each at a cost of more than $100 million.
The world may have firmly turned its attention — and funds — toward finding a vaccine for COVID-19 since the outbreak began in December 2019, but the difference in these timelines is not just about politics and money, Streeck said.
It also has to do with the unique composition of both viruses.
"SARS-CoV-2 [the virus causing COVID] and HIV cannot be compared in terms of structure and complexity," Streeck told DW. The human immunosuppressive virus (HIV) is "a completely different virus," he said.
Unlike SARS-CoV-2, which is a very stable virus, the human immunosuppressive virus (HIV) is extremely variable — it's constantly mutating. That makes it very difficult for HIV-infected people’s immune systems to make the right antibodies to fend off the virus, as it's usually a step ahead of any response in the body. There are thousands upon thousands of HIV strains
circulating in the global population. The HIV genome also integrates into the body's DNA, effectively making itself invisible to the immune system.
These characteristics mean our bodies don't usually mount an effective immune response to HIV.
They also make it very difficult to design a broadly effective vaccine.
Most vaccines work by stimulating 'neutralizing antibodies', which are proteins that attack unwanted invaders in the body. But when the target of that attack is constantly changing its appearance, it's very hard to capture.
"Science and the globe have been very fortunate that SARSCoV-2 is an easy target for vaccines," said Jonathan Weber, dean of medicine at Imperial College London and long-term HIV researcher.
All of the methods that vaccine developers have trialed to make a vaccine for COVID — including viral vector, mRNA, and adenovirus — "all of them have worked," Weber said.
"With HIV, the opposite is true. We've tried all those different techniques and none have protected against HIV in an effective way," he said.
Trials of HIV vaccines also tend to take much longer because, at the same time researchers want to test whether the vaccines they develop can prevent people from being infected with HIV, they're also actively helping prevent infections with pre-exposure prophylaxis (PrEP).
HIV vaccines in progress
To date, only one HIV vaccine, called Uhambo, showedpartial protection in human trials, but it was not effective in a recent large trial in South Africa.
Two other large trials, called PrEPVacc and Mosaico are currently underway. Both are using a combination approach to vaccination.
Mosaico is based on an adenovirus vaccine followed by a booster that contains a 'mosaic' of proteins from multiple HIV strains. This is similar to the Johnson and Johnson, OxfordAstraZeneca and Russian Sputnik COVID-19 vaccines.
Streeck, who's research team is involved in supporting the Mosaico trial in Europe and North and South America, says the researchers are "cautiously optimistic" after the vaccine showed promising results in animal testing. The researchers expect to have results within the next month.
PrepVacc uses HIV-DNA, a live viral vector and a protein. Researchers from the African-led, European-supported trial plan to enroll around 2000 HIV-negative volunteers.
Weber's team is leading the trial, currently being carried out in South Africa, Tanzania and Uganda. Although it began in 2018, progress has been "massively delayed by COVID" he said, and, so far, only about 300 participants have been signed up. "We think we'll have to run this study until early 2024 to get reliable results on whether the vaccine is effective," Weber told DW.
Meanwhile, vaccine- giant Moderna is working on two mRNA HIV vaccine possibilities. The first, called mRNA-1644, is expected to begin Phase I trials at the end of 2021.
The second, known as mRNA-1574, is being researched in collaboration with the National Institutes of Health (NIH) in the US. Researchers working on this second mRNA vaccine type have so far seen some promising results in monkeys, said Peng Zhang, immunologist from the National Health Institute in the United States.
"The preliminary results were very exciting. We tested different strains from different regions, from South Africa, Asia and America, and they were all neutralized by the monkeys receiving the vaccine," he told DW. The mRNA approach has been used by Moderna and BioNTechPfizer for their COVID-19 vaccines.
While mRNA vaccines have so far shown to be hugely successful against SARS-CoV-2,
Weber cautions that it is too early to hail them as the next big thing in HIV vaccine research.
"My own view at this stage before I have seen any data, is that we still have the problem [with mRNA vaccines] that we don't have the optimal antigen for HIV," he said.
' We need to use this momentum'
Despite the hurdles, Weber is convinced scientists will eventually crack the formula to find a safe and effective HIV vaccine.
"I've gone through my entire career believing we'll get an HIV vaccine. I’m not giving up on that — I only hope I can live to see it," he said.
In the last 40 years, more than 35 million people have died from HIV/AIDS. And according to Streeck, it is a pandemic "we are far from controlling."
"Most people that get infected die from this disease," he said. "There’s a momentum in the world right now. We need to use this momentum to end HIV and AIDS."
vaccination is slowing down.
Richard and Susanne wouldn't say they were against vaccines in principle. They got the standard vaccines when they were kids. But they say they don't trust the vaccines for COVID-19.
Their friends and acquaintances don't understand. They say they have experienced rejection and a lack of understanding.
"They think the vaccine makes them immortal. But they could still get infected, despite the vaccine," says Susanne indignantly.
Calculated risk?
But a vaccine can decrease your risk of a severe infection, I say.
"That may well be, but it's no more than a risk-benefit analysis. You can get infected with anything, anytime," says Richard. "But even if it does happen ... I have a lot of colleagues and friends who've had COVID-19 and their symptoms were either weak or it was just like a normal flu."
Susanne jumps in: "You hear these stories about severe cases and deaths in the media. That people have died either directly or indirectly because of COVID-19. But if you then ask how old they were, you find out they were already 87 or something. That just doesn't convince me to get a vaccine."
Germany's Federal Statistical Office (DESTASIS) says there were about 36,300 deaths from COVID-19 in the country last year.
In its most recent report, DESTASIS says that in about 30,100 cases in 2020, COVID-19 was the cause. And in a further 6,200 cases, COVID-19 was an accompanying disease.
Many of those who died due to a COVID infection were indeed older or elderly people. But they were certainly not the only ones who died.
But it also has a lot to do with how you live, say Richard and Susanne: "We don't live in the city, we don't go to any clubs, and we don't hug everyone we meet. I think we can calculate our risk."
COSMO Study on vaccine willingness
People's willingness to get vaccinated in Germany is decreasing. In a study called COSMO, 41% of those asked said they wanted to get vaccinated. That's much lower than at the start of June, when 57% of participants wanted to get vaccinated. Run by the University of Erfurt with the Robert Koch Institute and other research bodies, the study involved 1,011 people.
Many were inclined to weigh the pros and cons, just like Richard and Susanne. They lacked trust in the vaccines; or they felt they needn't bother with so many other people vaccinated.
"If you're worried about COVID-19, get vaccinated. But the chances of my getting infected are a lot lower, now that so many other people are vaccinated," says Susanne.
Distorted images in the media?
Richard and Susanne also feel the media has exaggerated the risks of COVID-19.
"It's always the same experts and always the same opinions," says Richard.
"Naturally, the images out of India were shocking, but can we really compare our situation with theirs? Just look at the hygiene standards there and the terrible state of their hospitals! I bet almost every disease turns into a catastrophe there. But that's not the case here," he says.
Susanne picks up the lead: "Take all that wrangling about AstraZeneca — there were conflicting statements. Or mix-andmatch vaccinations." She points to how experts and agencies were at first against mixing and matching vaccines, but now at least partially support it.
"And vaccines for kids. In America, they tried it on a few hundred kids, and based on that the FDA [United States Food and Drug Administration] decided it was okay to vaccinate all kids and young people," she continues. Some European countries are also ready to approve vaccination of children, but many agencies still think it's too risky. "And that's 'based on science,' is it?"
The two of them seem pretty wound up as they bat the arguments back and forth. You can tell they often deal with critique.
"We've definitely spent more time thinking about the issues than someone who's naively taken the jab," says Susanne.
Vaccination as a job requirement
The researchers behind the COSMO study say vaccination programs in workplaces or in the education sector may improve access to vaccination. In their report, the experts write that this would make it easier to reach groups of people who are in contact with lots of other people.
When I suggest that some employers may even want to make vaccination mandatory, Susanne and Richard get pensive.
"That would be a problem," says Susanne, "Not everyone wants it, but it is conceivable that our employers might demand it. And if you refuse, they may see that as grounds to make you redundant or not extent your contract. They do that in Russia. It probably wouldn't be legal here, but it is possible."
"I could get vaccinated through my employer right now," Susanne adds.
After that, there's a moments' silence. We watch the other people in the park, who seem to be enjoying their reclaimed normal lives.
Parting words
"Stay healthy," I wish the two as we part.
They nod, a little agonized: "You too," they say. "And please don't write us up as crazies. We just feel that everyone should be able to decide for themselves whether they want a vaccine or not. This is our decision, our risk, and everyone else should just accept it."
I leave the two sitting in the park and start to wonder whether I should have tried to persuade them to change their minds. And if so, how? I wonder whether their vaccine status is even actually my business, or to what extent they really should be allowed to decide for themselves.
My biggest takeaways from our conversation is that Susanne and Richard are annoyed about confusing information in the media and one-sided reports, and tas a result feel anxious and insecure about the situation.
But I still don't understand a lot of their arguments. And the counter-arguments I did pose don't seem to have moved them much, either. It leaves me confused, with a lasting feeling of incomprehension — which is probably mutual.
produced on a mass scale. With COVID-19, manufacturers aim to produce billions of doses by the end of 2021.
Second, logistics experts have to ensure appropriate distribution of the vaccine, and political leaders have to decide who gets the vaccine first.
Read more: Can a vaccine be given out fairly?
In the end, though, it will be up to each individual to decide. A 2020 survey of more than 13,000 people in 35 countries most affected by COVID-19 showed that the majority of people asked would choose to get vaccinated.
A survey by YouGov in January found that the willingness to be vaccinated increased in some European countries, whereas the trend isn't as clear in other regions of the world.
How fast can vaccines be developed?
It can take several years to develop an effective and safe vaccine. On average, it takes between 10 and 12 years, but it can take longer. The search for a vaccine against HIV has been going since the early 1980s — so far without success.
In the case of COVID-19, researchers are racing to shorten the time it usually takes because of the ongoing pandemic. Despite the pressure that that brings, vaccine developers, manufacturers and the World Health Organization (WHO) say there will be no compromises on safety.
Research teams are aiming to accelerate, or limit, the time it takes to get to approval during the pandemic to an average duration of 16 months.
That will only be the beginning. Once clinical trials are successfully completed and a vaccine is approved and produced, researchers start phase IV, during which they observe the progress of vaccinated patients.
Which types of COVID-19 vaccine are in development?
Researchers are pursuing 13 different approaches for vaccines against COVID-19.
Most of the vaccine candidates use a protein-based subunit — so, instead of using a complete pathogenic virus, they are built on a small component of it, such as a protein found in its outer shell.
That protein is administered to patients in a high dose, with the aim of inducing a fast and strong reaction by the human immune system.
The hope is that the immune system will "remember" the protein and trigger a similar defense reaction if or when it comes into contact with the actual virus.
Vaccines against hepatitis B and HPV ( human papillomavirus), for example, are based on this principle.
Four additional approaches have made it to phase III.
Nonreplicating viral vectors are a type of so-called recombinant vaccines: Researchers modify the virus's genetic information by switching on or off or altering certain functions. By doing that they can, for example, reduce the infectiousness of a virus. Such genetic modifications, however, require that science already has detailed knowledge about which parts of a virus' genetic material are responsible for which functions in order for them to be able to manipulate them effectively. The term "nonreplicating" means that the virus in the vaccine enters cells in the human body but is unable to reproduce there on its own.
Inactivated vaccines use a "dead" version of the pathogen. They tend to provide a lower level of protection than live vaccines. Some vaccines in this class have to be administered several times to achieve sufficient immunity. Examples of inactivated vaccines include ones against influenza and hepatitis A.
RNA vaccines follow a different strategy, without using any "real" component of the virus at all. Instead, researchers aim to trick the human body into producing a specific virus component on its own. Since only this specific component is built, no complete virus can assemble itself. Nevertheless, the immune system learns to recognize the non-human components and trigger a defense reaction.
Vaccines based on viruslike particles use another approach: Researchers only use the empty virus envelope — without any genetic material inside of it — to train the immune system.
With DNA-based vaccines, patients are injected with the virus's genetic makeup for the human body to produce virus particles itself without being actually infected. Confronted with these self-produced virus particles, the immune system is supposed to learn to recognize and fight the actual virus.
Who is working on a COVID-19 vaccine?
At time of writing, there were well over 100 research teams worldwide developing a COVID-19 vaccine. So far, 29 teams have advanced their vaccines to the third phase of clinical trials. Although some of these vaccines have already been approved in some countries, they still continue to be tested in clinical trials in parallel.
Five teams stand out for conducting the most extensive clinical trials:
Belgian company Janssen Pharmaceutical is testing its candidate vaccine, which is based on a nonreplicating viral vector, on about 576,000 people in South Africa, Belgium, the United States, Argentina, Brazil and Colombia.
The US companyModerna is testing its RNA-based vaccine on 79,000 people in the US, Canada, France and Japan
In a public- private partnership between the University of Oxford and the British company AstraZeneca, researchers are testing their vaccine candidate on approximately 66,000 people in the US, Chile, Peru and the UK. Their vaccine is based on a similar principle to Janssen's.
The Chinese company Sinopharm is working in various constellations with the Beijing Institute and Wuhan Institute. Taking all trial series together, they are testing an "inactivated" vaccine on around 61,000 people in Bahrain, Jordan, Egypt, Morocco, Argentina and Peru.
A German company, BioNTech, is pursuing a different approach: It is focusing on RNAbased technology and testing the BioNTech-Pfizer candidate vaccine on about 49,000 people in the US, Argentina and Brazil, among other countries.