Earlier this week the Deputy Chief Medical Officer of England, Jonathan Van-Tam, said the words no one wanted to hear: "We can't be sure we're going to get a vaccine."
By theory, the vaccines are straightforward but in reality complex. The perfect vaccine protects against infection, prevents it from spreading and is safe to do so. But, as vaccine timelines show, none of this is easily achieved.
We have no vaccine more than 30 years after scientists areolated from HIV, the virus that causes Aids. The dengue fever virus was reported in 1943, but only last year was the first vaccine approved, and even then it made some people's infection worse. Mumps had been the fastest vaccine ever produced. It lasted four years.
Scientists have already focused on coronavirus vaccines, but do not start from scratch. Two coronaviruses have already triggered lethal outbreaks, namely Sars and Mers, and vaccine work for both has gone ahead. But none have been approved, partly because Sars has fizzled out and Mers to the Middle East is national. The lessons learned will help scientists create a Sars-Covid vaccine but there is still a great amount to know about the virus.
A major concern is that coronaviruses do not have a propensity to cause long lasting immunity. Human coronaviruses cause about a quarter of common colds, but the immune response declines so quickly that people may become reinfected the next year.
Oxford University researchers recently analyzed blood from recovered Covid-19 patients and found that levels of IgG antibodies – those responsible for long-lasting immunity – increased steeply in the first month of infection but then started to fall again.Last week, researchers at New York's Rockefeller University found that most people who recovered from Covid-19 without going to hospital did not produce many killer antibodies to the virus.
"That's what's particularly difficult," says Stanley Perlman, a University of Iowa veteran coronavirus researcher. "What is a vaccine going to do if the normal infection doesn't give you too much immunity even when it's a serious infection? It might be safer, but we don't know. "The virus would be with us for some time if a vaccine only protects for a year.
The virus' genetic stability matters, too. Some viruses, such as influenza, mutate so rapidly that developers of vaccines must release new formulations annually. A big reason we don't have a vaccine for the disease is the rapid development of HIV.
So far, the coronavirus Sars-CoV-2 appears relatively stable, but it acquires mutations, as all viruses do. Several genetic variations were found in the protein "spikes" of the virus which are the basis of most vaccines. Unless the spike protein mutates too soon, it will potentially outdate the antibodies developed by a vaccine and may not bind the virus potentially enough to avoid infection.
Martin Hibberd, professor at the London School of Hygiene and Tropical Medicine for emerging infectious diseases, who helped classify some of the mutations of the virus, called them "an early warning"
By theory, the vaccines are straightforward but in reality complex. The perfect vaccine protects against infection, prevents it from spreading and is safe to do so. But, as vaccine timelines show, none of this is easily achieved.
We have no vaccine more than 30 years after scientists areolated from HIV, the virus that causes Aids. The dengue fever virus was reported in 1943, but only last year was the first vaccine approved, and even then it made some people's infection worse. Mumps had been the fastest vaccine ever produced. It lasted four years.
Scientists have already focused on coronavirus vaccines, but do not start from scratch. Two coronaviruses have already triggered lethal outbreaks, namely Sars and Mers, and vaccine work for both has gone ahead. But none have been approved, partly because Sars has fizzled out and Mers to the Middle East is national. The lessons learned will help scientists create a Sars-Covid vaccine but there is still a great amount to know about the virus.
A major concern is that coronaviruses do not have a propensity to cause long lasting immunity. Human coronaviruses cause about a quarter of common colds, but the immune response declines so quickly that people may become reinfected the next year.
Oxford University researchers recently analyzed blood from recovered Covid-19 patients and found that levels of IgG antibodies – those responsible for long-lasting immunity – increased steeply in the first month of infection but then started to fall again.Last week, researchers at New York's Rockefeller University found that most people who recovered from Covid-19 without going to hospital did not produce many killer antibodies to the virus.
"That's what's particularly difficult," says Stanley Perlman, a University of Iowa veteran coronavirus researcher. "What is a vaccine going to do if the normal infection doesn't give you too much immunity even when it's a serious infection? It might be safer, but we don't know. "The virus would be with us for some time if a vaccine only protects for a year.
The virus' genetic stability matters, too. Some viruses, such as influenza, mutate so rapidly that developers of vaccines must release new formulations annually. A big reason we don't have a vaccine for the disease is the rapid development of HIV.
So far, the coronavirus Sars-CoV-2 appears relatively stable, but it acquires mutations, as all viruses do. Several genetic variations were found in the protein "spikes" of the virus which are the basis of most vaccines. Unless the spike protein mutates too soon, it will potentially outdate the antibodies developed by a vaccine and may not bind the virus potentially enough to avoid infection.
Martin Hibberd, professor at the London School of Hygiene and Tropical Medicine for emerging infectious diseases, who helped classify some of the mutations of the virus, called them "an early warning"
Another challenge: safeguarding every vaccine
Safety must remain a priority in the rush to develop a vaccine-there are now more than 100 in development. Like experimental medications for the seriously ill, theoretically billions of relatively healthy people will receive the vaccine.
It means scientists would need to check for signs of adverse side-effects extremely carefully. Scientists discovered during the 2004 hunt for a Sars vaccine that one candidate had induced hepatitis in ferrets. Another significant problem is the "antibody-induced enhancement" in which the vaccine-producing antibodies potentially cause potential infections worse. The result caused significant lung damage to both Sars and Mers in animals given experimental vaccines.
John McCauley, director of the Francis Crick Institute's Worldwide Influenza Centre, says it requires time to consider the unique problems that each vaccine faces. "You don't know the difficulties, the specific difficulties each vaccine can cause you," he says. "And we don't have any experience with this virus or the virus components."
The coronavirus vaccine is not successful at 100 percent.
Those in development use at least eight different approaches, ranging from weakened and inactivated viruses to technologies that smuggle genetic code into the cells of the recipient, which then churn spike proteins for the immune system to make antibodies.
Ideally, a vaccine would produce constant, high levels of antibodies to wipe out the virus, and "T" cells to kill infected cells as well. But every vaccine is different and nobody knows what kind of immune response is good enough today.
"We don't even know if a vaccine can produce an immune response that would protect against future infection," says David Heymann, who led the WHO's response to the Sars epidemic.
Recent results of two contender vaccines indicate that they could have some use.
The U.S. pharmaceutical company Moderna reported levels of antibodies close to those observed in 25 people who obtained its vaccine in recovered patients.
Another Oxford University vaccine did not protect monkeys from contracting the virus but did appear to prevent pneumonia, a significant cause of death in patients with coronavirus.
When humans respond the same way, people who have been vaccinated will still spread the virus but are less likely to die of it.
How well a vaccine works dictates how the vaccine is used. Armed with a highly effective vaccine that protects the herd immunity for several years, countries could aim to protect at least two-thirds of the population.
In average, coronavirus patients pass the virus on to three people, but if two or more patients are immune, the outbreak will fizzle out. This is the safest case.
Most likely we will end up with a vaccine that is only marginally effective, or a number of vaccines.
Vaccines containing compromised strains of the virus can be harmful to older people, but should be provided to younger people with more active immune systems to minimize infection spread.
During the meantime, older people can get vaccinations that would actually prevent infections from progressing to life-threatening pneumonia. "If you don't have the potential to induce immunity, then you need to develop a plan to reduce severe infection outcomes," McCauley says.
Yet partially successful vaccines have their own problems: a vaccine that doesn't stop the replication of the virus will facilitate the development of resistant strains, rendering the vaccine redundant.
How will we live with the virus?
Citizens are going to have to adapt-and life will change. Heymann says we'll have to get used to extensive infection monitoring backed by swift containment of the outbreak. People also have to play their part by keeping handwashing, physical distancing and avoiding gatherings, especially in enclosed spaces. Repurposed drugs are faster to test than vaccines, so we might have an antiviral or an antibody treatment that works before there is a vaccine available, he adds. Immediate treatment when symptoms arise may reduce the mortality risk, at least.