The vaccine, developed by scientists at the Jenner Institute of Oxford University, showed up to 77% efficacy in a trial of 450 children in Burkina Faso over 12 months.

The hunt for a malaria vaccine has been going on the best part of a century. One, the Mosquirix vaccine developed by GlaxoSmithKline, has been through lengthy clinical trials but is only partially effective, preventing 39% of malaria cases and 29% of severe malaria cases among small children in Africa over four years. It is being piloted by the World Health Organization in parts of Kenya, Ghana and Malawi.

The Oxford vaccine is the first to meet the WHO goal of 75% efficacy against the mosquito-borne parasite disease. Larger trials are now beginning, involving 4,800 children in four countries.

Prof Adrian Hill, director of the Jenner Institute, where the Oxford/AstraZeneca Covid vaccine was invented, said he believed the vaccine had the potential to cut the death toll dramatically. “What we’re hoping to do is take that 400,000 down to tens of thousands in the next five years, which would be absolutely fantastic.”

Other interventions, such as impregnated bednets and malarial drugs, have reduced the death toll from a million a year, he said, and those must continue. But, if the vaccine could cut deaths to the tens of thousands, they might be able to look towards “a greater goal – eventually eradicating malaria”.

Hill said the institute might apply for emergency approval for the malaria vaccine just as it did for the Covid jab. “I’m making the argument as forcefully as I can, that because malaria kills a lot more people than Covid in Africa, you should think about emergency-use authorisation for a malaria vaccine for use in Africa. And that’s never been done before.”

The institute would probably ask the regulatory bodies in Europe or the UK for a scientific opinion on the vaccine and then apply to the World Health Organization for approval for use in Africa. “They did Covid in months – why shouldn’t they do malaria in a similar length of time as the health problem is an even greater scale in Africa?” Hill said.

The vaccine will be manufactured at large scale and low-cost, say the researchers, who have arranged a deal with the Serum Institute of India, which is involved in manufacturing the Oxford/AstraZeneca Covid-19 vaccine.

The Serum Institute has had to delay supplies of the Covid vaccine to the rest of the world because of the huge rise in cases in India, but has promised to deliver 200m doses a year of the malaria vaccine if it is licensed.

Hill said the best-case scenario was approval by the end of 2022, by which time the Serum Institute would have plenty of capacity.

Dr Cyrus Poonawalla and Adar Poonawalla, respectively chair and CEO of the Serum Institute, said in a statement that they were “highly excited to see these results on a safe and highly effective malaria vaccine which will be available to the whole world”. The project was through collaboration with Oxford and also Novavax, which is supplying the adjuvant, a substance that enhances the immune system response.

“We are highly confident that we will be able to deliver more than 200m doses annually in line with the strategy, as soon as regulatory approvals are available,” they said.

The children in the trial, which is published in the Lancet journal, were five to 17 months old and lived in Nanoro, an area encompassing 24 villages with an approximate population of 65,000 people. They were split into three groups; two had the vaccine, but with either a low or high dose of adjuvant, while the third group were given a rabies vaccine, so acted as a control.

The children had three doses and have since had a further booster jab. The Mosquirix vaccine is also given as four doses.

Hill said mothers were keen to bring their children back for further shots because of their experience of malaria. Efficacy was 77% in the high-dose adjuvant group and 74% in the lower dose group.

Gareth Jenkins, of Malaria No More UK, said: “We can end malaria in our generation but only if governments invest in the research needed to deliver the new medicines and products that can accelerate the end of this terrible disease.

“The Jenner Institute’s groundbreaking work on both the new Covid-19 and malaria vaccines is a great example of this and demonstrates just how much humanity’s safety is dependent on new science.

“An effective and safe malaria vaccine would be a hugely significant extra weapon in the armoury needed to defeat malaria, which still kills over 270,000 children every year. For decades British scientists have been at the forefront of developing new ways to detect, diagnose, test and treat malaria, and we must continue to back them.

“A world without malaria is a world safer both for the children who would otherwise be killed by this disease, and for us here at home. Countries freed from the malaria burden will be much better equipped to fight off new disease threats when they inevitably emerge in the future.”

The man, a resident of the city of Zhenjiang, was hospitalised on April 28 after developing a fever and other symptoms, the NHC said in a statement.

He was diagnosed as having the H10N3 avian influenza virus on May 28, it said, but did not give details on how the man had been infected with the virus.

The man was stable and ready to be discharged from hospital. Medical observation of his close contacts had not found any other cases.

H10N3 is a low pathogenic, or relatively less severe, strain of the virus in poultry and the risk of it spreading on a large scale was very low, the NHC added.

The strain is "not a very common virus," said Filip Claes, regional laboratory coordinator of the Food and Agriculture Organization's Emergency Centre for Transboundary Animal Diseases at the Regional Office for Asia and the Pacific.

Only around 160 isolates of the virus were reported in the 40 years to 2018, mostly in wild birds or waterfowl in Asia and some limited parts of North America, and none had been detected in chickens so far, he added.

Analysing the genetic data of the virus will be necessary to determine whether it resembles older viruses or if it is a novel mix of different viruses, Claes said.

Many different strains of avian influenza are present in China and some sporadically infect people, usually those working with poultry. There have been no significant numbers of human infections with bird flu since the H7N9 strain killed around 300 people during 2016-2017.

No other cases of human infection with H10N3 have previously been reported globally, the NHC said.

Their optimism rested on solid science: Researchers knew that people produce antibodies to the human immunodeficiency virus that causes AIDS. And spurring the body to produce antibodies was already a common and successful vaccine strategy that had drastically reduced cases of measles, smallpox, and many other diseases. Tackling AIDS seemed equally doable.

“We thought that it was going to be a piece of cake,” says Esparza, a former senior advisor at the Bill & Melinda Gates Foundation, who is now affiliated with the University of Maryland School of Medicine. “We didn’t know the complexity of HIV.” More than three decades later, there is still no viable vaccine candidate for HIV, even as scientists have produced multiple effective vaccines for the SARS-CoV-2 virus that causes COVID-19 less than a year after it emerged.

Now, recent findings are sparking new hope. At an international AIDS conference in February, researchers from Scripps Research and IAVI, a nonprofit vaccine research organization, announced promising blood-test results from the first phase one human trial of a new HIV vaccine strategy. The results, which are still unpublished, grabbed the public’s attention in a way that could only be possible in the era of social media. “THIS IS HUGE,” read a tweet by Twitter user @AugustusRotter. The tweet was liked and retweeted many thousands of times in early April.

The reality is far more nuanced than the hype suggests, says William Schief, an immunologist at Scripps and executive director of vaccine design at IAVI's Neutralizing Antibody Center. Although the immune response his team detected is an important proof-of-concept finding, he says, the field is still years away from producing shots that make people less likely to be infected with HIV. Even then, an eventual vaccine will likely include multiple shots, which may be a tough sell.

“Scientifically, it is a beautiful concept,” Esparza says. “Practically, it will not be easy to implement.”

Still, after decades of setbacks, the results are welcome news—with some intriguing connections to the COVID-19 vaccine effort that may help accelerate the HIV work.

“It’s kind of a small step toward making an HIV vaccine, but it's also a gigantic step,” suggesting a viable path forward, Schief says. “And in fact, in this particular case, it worked amazingly well.”

Three waves of hope

The search for an HIV vaccine began soon after scientists isolated the virus and confirmed that it caused AIDS in 1984. Since then, the scientific quest has followed three waves of research, says Esparza, who published a historical account of the search for an HIV vaccine in 2013.

The first wave focused on the most established idea: trying to stimulate the human immune system to produce so-called neutralizing antibodies, which inactivate specific viruses. This is the strategy that many other vaccines use, including those for COVID-19. For years, researchers worked to identify the antibodies that people produced as they responded to HIV infection, and then develop vaccines that would induce the production of similar antibodies.

But HIV turned out to be an elusive enemy. Antibodies target specific proteins on the surface of a virus. However, HIV mutates rapidly into variants that the antibodies can’t recognize, which means it continuously stays one step ahead of the immune system. In one classic study, Schief says, researchers repeatedly tested the blood of people infected with HIV and found that the antibodies produced by their immune systems were always about three to six months behind the virus.

“HIV is still a much tougher scientific target,” than SARS-CoV-2, says Larry Corey, an expert in virology, immunology and vaccine development at the Fred Hutchinson Cancer Research Center in Seattle, and principal investigator of the HIV Vaccine Trials Network. “Ninety-eight percent of humans recover from SARS-CoV-2, and we are zero out of 78 million of self-recovery for HIV.”

By the early 2000s, researchers were pursuing a second wave of HIV vaccines, based on the idea of targeting the body’s soldier-like “killer” T cells instead of trying to stimulate antibodies. Long-term human immunity depends on two main groups of cells: B cells and T cells. Both help produce antibodies, but T cells also seek out and destroy infected cells. The idea for T-cell vaccines was to stimulate cells that recognize internal proteins in the virus.

In 2007, that idea not only failed to provide protection in a double-blind, randomized phase two trial called STEP, it also appeared to increase the risk of HIV infection. “The trial failed miserably,” Esparza says.

That was far from the only vaccine attempt to fizzle. After decades of human trials, only one has shown any degree of real-world effectiveness. Completed in 2009 in Thailand, a combination of two vaccines, which took the wave-one strategy of inducing antibodies, reduced rates of HIV infection by 31 percent—not enough to gain regulatory approval.

Targeting naïve B cells

The third and current wave of HIV vaccine research began in the late 2000s, when researchers discovered that a small minority of people infected with HIV produce particularly potent antibodies that can neutralize many strains of HIV at once. So far, scientists have identified dozens of these broadly neutralizing antibodies, which target parts of the viral surface (much like the spike proteins on SARS-CoV-2) that are consistent from strain to strain.

People who make these proteins still cannot fight off HIV because their bodies don’t make these antibodies until after the viral infection has taken hold, and the virus continues to mutate in the meantime, Schief says. But the discovery sparked a new idea: Maybe an effective vaccine could get a step ahead of the virus by targeting so-called naïve B cells (also known as precursor cells), which circulate in our blood, Schief says. If a vaccine could cause naïve B cells to acquire mutations that transform them into cells that produce broadly neutralizing antibodies before an HIV infection, the body might be able to fight it off when presented with the virus for the first time.

In 2010, Schief’s group began to work with a class of broadly neutralizing antibodies called VRC01, the first to be discovered by the NIH Vaccine Research Center. First, they developed an engineered protein nanoparticle that, they reported, [[http://doi.org/10.1126/science.aac5894. could bind to the naïve B cells]] in human blood samples. In mouse studies, the nanoparticle could activate these cells and get them to multiply and mutate toward producing VRC01-like antibodies. The new study aimed to find out if the same could happen in people.

It was a big “if.” Only one in every 300,000 or so naive B cells has the potential to develop into cells that produce VRC01 antibodies, Schief says. But in a complex analysis of blood, the team found that 35 of the 36 people who received the vaccine, an “engineered protein nanoparticle,” produced the intended B cell responses.

The findings, which are still undergoing analyses and have not yet been submitted for publication, are a long way off from showing any kind of protective effect against HIV, Schief says—even though plenty of exuberant social media users have made it sound as if an HIV vaccine is suddenly around the corner.

“Somebody sent out a tweet a week ago that indicated that our trial was inducing responses that could protect 97 percent of the vaccine recipients against HIV,” he says. “That's completely not true.”

Eventually, Schief says, people might get a succession of shots over weeks to years, beginning with one that starts where the new trial did: interacting with the right naïve B cells, to get the process started. Subsequent shots would guide the B cells to produce fully mature broadly neutralizing antibodies.

“We’re trying to take the driver's seat with the immune system and educate it step by step with a vaccine,” Schief says. The same idea could someday lead to vaccines for Zika, hepatitis C, malaria, and others, including a universal flu vaccine and future coronaviruses.

The work is also an important sign that scientists are on the right track, Corey says, adding to a recent study which found that giving people high levels of broadly neutralizing antibodies can prevent HIV.

Leveraging the vaccine infrastructure from COVID-19

In addition to the scientific challenges, HIV vaccine research has long been hindered by a missing sense of urgency. While public and political will, along with major industry investment, pushed the COVID-19 effort to move forward at record speeds, HIV is a disease that disproportionately affects marginalized groups, Esparza says, and pharmaceutical companies have not wanted to invest in expensive HIV trials until scientists established more of the basic science.

“If society really valued an HIV vaccine, we would have done several efficacy trials in parallel, as was done with COVID,” Esparza says. “Expensive, yes. But the cost of the HIV epidemic has been enormous.”

According to one study, health spending on HIV/AIDS totaled more than $562 billion across 188 countries from 2000 to 2015.

So as the world watches COVID-19 vaccines arrive with unprecedented speed, one hope is that the enthusiasm will provide momentum for the kinds of long-term vaccine development efforts that will be crucial to battling HIV.

The two are already connected. COVID-19 vaccine efforts piggybacked off of the clinical, laboratory, and biostatistical infrastructure created by the HIV Vaccine Trials Network, Corey says. For years, Schief adds, his group has collaborated with Moderna to test mRNA delivery of their proteins in animal models. They plan to work together to rapidly create HIV vaccine candidates for use in human clinical trials.

Given the enthusiasm for COVID-19 vaccines and the new mRNA technology that can produce vaccine variations quickly, this might be the time to generate new interest in the search for HIV vaccines, which will also require the public’s collaboration.

“If we come up with an HIV vaccine,” Schief says, “I would think the world's experience with the COVID vaccines might make it easier for us to deploy.”

But health officials have little clue where people caught the monkeypox virus. And there's concern the virus may be spreading through the community — undetected — and possibly through a new route of transmission.

"This [outbreak] is rare and unusual," epidemiologist Susan Hopkins, who's the chief medical adviser of the U.K. Health Security Agency (UKHSA), said in a statement on Monday.

"Exactly where and how they [the people] acquired their infections remains under urgent investigation," the agency said in the statement.

Monkeypox can be a nasty illness; it causes fever, body aches, enlarged lymph nodes and eventually "pox," or painful, fluid-filled blisters on the face, hands and feet. One version of monkeypox is quite deadly and kills up to 10% of people infected. The version currently in England is more mild. Its fatality rate is less than 1%. A case generally resolves in two to four weeks.

Typically, people catch monkeypox from animals in West Africa or central Africa and import the virus to other countries. Person-to-person transmission isn't common, as it requires close contact with bodily fluids, such as saliva from coughing or pus from the lesions. So the risk to the general population is low, the U.K. health agency notes.

But in England, 7 of the 8 cases don't involve recent travel to Africa, suggesting the patients involved in those cases caught the virus in England. On top of that, those individuals haven't had contact with the one patient known to have traveled to Nigeria, the UKHSA reported Tuesday. Together, this data suggests the virus is spreading in the community undetected.

"Presumably this is cryptic spread from an imported case(s)," virologist Angie Rasmussen of the Vaccine and Infectious Disease Organization tweeted on Monday.

In the U.S., the patient in Massachusetts had not recently traveled to countries where the disease occurs but had visited Canada.

In addition, there's evidence the virus could be spreading through a new route: sexual contact. "What is even more bizarre is finding cases that appear to have acquired the infection via sexual contact," epidemiologist Mateo Prochazka at the UKHSA tweeted. "This is a novel route of transmission that will have implications for outbreak response and control."

"We are particularly urging men who are gay and bisexual to be aware of any unusual rashes or lesions and to contact a sexual health service without delay," epidemiologist Hopkins said in the UKHSA's statement.

Scientists at the Centers for Disease Control and Prevention are watching the outbreak in Europe closely. "We do have a level of concern that this is very different than what we typically think of from monkeypox," Jennifer McQuiston, a senior CDC official, told health news site STAT on Tuesday.

In 2019, the U.S. Food and Drug Administration approved the first vaccine for monkeypox, which also protects against smallpox. "This vaccine is also part of the Strategic National Stockpile (SNS), the nation's largest supply of potentially life-saving pharmaceuticals and medical supplies for use in a public health emergency that is severe enough to cause local supplies to be depleted," the agency said in a news release.

A primer on monkeypox

So just what is known about monkeypox? And how threatening is it compared with other emerging viruses?

In 2017, Goats and Soda interviewed two monkeypox experts — Anne Rimoin of the University of California, Los Angeles, and Jay Hooper of the U.S. Army Medical Research Institute of Infectious Diseases — to find out.

Here are some of the questions we asked and some of their surprising answers, updated in light of the current cases.

Where does it come from? Monkeys?

No!

"The name is actually a little bit of a misnomer," Rimoin says. Perhaps it should be called "rodentpox" instead.

The name "monkeypox" comes from the first documented cases of the illness, in 1958, when two outbreaks occurred in colonies of monkeys kept for research, the CDC says on its website.

But monkeys aren't major carriers. Instead, the virus likely persists in squirrels, pouched rats, dormice or another rodent.

How do you catch it?

Primarily, from an animal bite, scratch or contact with the animal's bodily fluid. Then the virus can spread to other people through coughing and sneezing or contact with pus from the lesions.

The lesions from monkeypox are similar to those from a smallpox infection.

"But it doesn't spread very well between people," Hooper says. "Its infection rate is much lower than that of smallpox." In many cases, people don't spread the virus to anyone else.

Up until this current outbreak, a person sick with monkeypox spreads the virus to between zero and one person, on average. So all previous outbreaks (up until now) burned themselves out quickly.

"You have primary cases, in which people get monkeypox from an animal, and they may transmit the disease a few generations — but then that's it," she says. "The outbreaks tend to be self-limiting."

"There is no evidence, to date, that person-to-person transmission alone can sustain monkeypox infections in the human population," the World Health Organization's website says.

Scientists don't know yet if the rate of transmission has increased in this current outbreak. If there is enhanced transmission, that could be one reason the current outbreak appears to have spread through the community in three cities.

Has there ever been an outbreak in the U.S.?

"There already was!" Hooper says. "But it was quickly contained."

In 2003, monkeypox hitched a ride with a shipment of animals from Ghana to Illinois. Several giant pouched rats and squirrels tested positive for the virus and eventually spread it to prairie dogs being sold as pets in multiple states in the Midwest, the CDC says on its website.

Forty-seven people caught the disease from the prairie dogs. Everyone recovered. And no one spread the disease to another person.

Is monkeypox a "new" virus?

No. The virus has likely been infecting people for centuries, even millennia, Rimoin says. But for a long time, doctors missed the cases.

Monkeypox is closely related to smallpox. "They are clinically indistinguishable," Rimoin says. "So for centuries, doctors have likely mistaken monkeypox for smallpox."

Then in the 1970s, the world was close to eradicating smallpox. Cases plummeted. And doctors in central Africa started noticing another disease that looked like smallpox but didn't spread as well between people. It was monkeypox.

There are several other viruses related to smallpox, including cowpox and camelpox. "I would be more worried about camelpox than monkeypox," Rimion says, "because that's closer on the genetic tree to smallpox."

Is the disease actually a rising threat? Or are we just better at detecting it?

A little bit of both, Rimion says.

Back in 2010, Rimoin and her colleagues reported that monkeypox had increased 14-fold in the Democratic Republic of Congo since the 1980s. Incidence rose from less than 1 case per 10,000 people to about 14 cases per 10,000 people.

And the reason for this bump is ironic: the eradication of smallpox.

The smallpox vaccine actually works quite well to protect people against monkeypox. It's about 85% effective (although the smallpox vaccine does have some safety concerns, Hooper points out: "It's a live virus and can cause a deadly infection in people with severely compromised immune systems").

But after the world eradicated smallpox, countries stopped vaccinating kids. And for those who were vaccinated years earlier, their protection has likely waned over time, Hooper says.

"So now there's this growing population of people who don't have immunity to monkeypox," he says. "And when you do have a outbreak, it's likely to be bigger because less people in the community are protected."

That means small monkeypox outbreaks in West Africa and central Africa now involve dozens of cases instead of just one or two, Hooper says.

And in the Democratic Republic of Congo, annual cases have shot up into the thousands. In 2020, there were nearly 4,600 suspected cases, according to a study published in February.

Could the virus become more transmissible and thus more of a global threat?

"Oh, yes," Hooper says. "Every time there's an outbreak — and the more people get infected — the more chances monkeypox has to adapt to people," he says.

In other words, the more time the virus spends inside people, the more time it has to evolve. It could possibly figure out how to spread more quickly among people.

So scientists are keeping a close eye on the virus and outbreaks that occur — especially if the virus appears to change its route of transmission, as may be happening in the current outbreak.

"We didn't think Ebola spread very easily between people," Hooper adds. "And we were all surprised that health care workers could catch it even though they were wearing protective gear."

And of course, many scientists didn't think SARS-CoV-2, the coronavirus that causes the disease COVID-19, would mutate to become more contagious, but that's exactly what has happened in the past two years. SARS-CoV-2 evolved from a virus just about as contagious as the flu virus into one that's almost as contagious as the far more transmissible chickenpox virus.

"With viruses that spill over from animals, you just never know what's going to happen," Hooper says.

And indeed, this new outbreak in Europe may be a sign that the virus has changed — even if just a bit — and may be increasing its ability to spread among people.