LONDON As West Africa's devastating Ebola outbreak begins to dwindle, scientists are looking beyond the endgame at the kind of next-generation vaccines needed for a vital stockpile to hit another epidemic hard and fast.
Determined not to lose scientific momentum that could make the world's first effective Ebola interventions a reality, researchers say the shots, as well as being proven to work, must be cheap, easy to handle in Africa and able to hit multiple virus strains.
That may mean shifting focus from the stripped-down, fast-tracked vaccine development ideas that have dominated the past six months, but it mustn't mean the field gets bogged down in complexities.
"We need a stockpile because there will be other outbreaks," said Seth Berkley, chief executive of the GAVI global immunization alliance, which helps bulk-buy vaccines for poor countries.
The experimental vaccines now moving into large clinical trials in West Africa target the current Ebola Zaire virus strain, but the next outbreak may be different.
"We need to work with the pharmaceutical industry to create second-generation vaccines that would cover not just Ebola Zaire but also Ebola Sudan and perhaps Marburg, perhaps Lassa. The idea is to have vaccines that will work across different places," Berkley said.
Right now, scientists are grappling with several tricky issues -- partly due to success in cutting new infections in the vast Ebola outbreak.
With relatively few new cases, big trials in Liberia and Sierra Leone to test the first generation single-dose one strain vaccines may not have the statistical power needed to show whether the shots work.
And already, early data from safety trials in humans suggest a single-dose vaccination with the most advanced vaccine, from GlaxoSmithKline, may not provoke an immune response strong enough to protect people exposed to the virus.
"We now know you get around 10 times fewer antibodies in humans (than in monkeys) and probably five times fewer T-cells," said Adrian Hill of Oxford's Jenner Institute, referring to two key elements of the immune system.
This strongly suggests that a two-dose regime, or a so-called "prime-boost" approach, is the one likely to prove effective, Hill said.
These and other issues add up to a sizeable to do list for scientists focusing on vaccines for future stockpiles.
Producing multi-strain, or multivalent, vaccines that could protect against different types of Ebola and other hemorrhagic fevers will be more time consuming than making today's monovalent shots, but it is by no means impossible.
In fact, several of the candidate Ebola vaccines being fast-tracked through testing started out as multivalents before being stripped back to deal with the current outbreak.
Another challenge is ensuring vaccines have a long shelf-life and can be easily transported in the tropics. At the moment, test shots are kept at -70 or -80 degrees Celsius, although Johnson & Johnson says its Ebola vaccine can be stored at normal fridge temperature for many weeks.
Producing adequate volumes, however, looks manageable. Hopefully, the next time Ebola emerges from Africa's forests it will be spotted earlier and immunization will be needed for perhaps tens of thousands of people -- nothing like the tens of millions who would need vaccines in a worldwide flu pandemic.
Finally companies still need a regulatory green light, which gets tricky if large-scale trials fail to produce clear proof that the shots are both safe and effective in people.
Researchers and drugmakers say, however, that regulators have made clear stockpile Ebola vaccines could be approved on efficacy data from tests in monkeys or other non-human primates plus proof of safety and immune response in humans, reflecting contingency plans for vaccines designed for bioterror attacks.
Pursuing tomorrow's vaccines is not to say one of today's monovalent shots from GSK, Merck or J&J might not yet have a role in ring-fencing lingering pockets of infection in the current epidemic, and perhaps finally stamping it out.
"I'm pretty optimistic there's still a role for vaccination in ending this outbreak," said Hill. "And I'm certainly optimistic that we'll learn for the next outbreak which of these vaccine approaches is the most likely to work, and be ready to tackle it early on."
(Editing by Anna Willard)