Plague, Flu and Zika: could 2017 bring vaccines for all three?

The global health community has reinvigorated its search for vaccines against epidemics, pandemics and bioterrorist threats. Elly Earls profiles three of the most promising contenders.


vaccine

With threats of epidemics, pandemics and bioterrorism high on the global health agenda, many pharmaceutical and biotech firms, as well as academic institutions, are doubling down on developing new vaccines to combat the spread of diseases. Meanwhile, government bodies and public-private coalitions are looking more closely at how to speed the process of getting these vital drugs to the market.

But it’s no easy task, with challenges including identifying the source of emerging diseases; developing new detection measures to understand their epidemiology; limiting their spread (which is becoming increasingly difficult due to international trade and travel); and distributing the necessary drugs and vaccines to the population.

But, according to Ted Fjällman, PhD, CEO of Prokarium, a UK synthetic biology company that has secured £2m from UK and Mexican Government contracts to develop vaccines against plague, Zika, bacterial diarrhoea and enteric fever, the biggest challenge is to speed up the R&D of new vaccines and allow clinical trials to be performed in a fast track mode, if and when there are signs of an epidemic unfolding.

“In certain situations, it may be worthwhile to consider streamlining regulatory requirements to allow slight variations of vaccines to be brought to market without all the usual long-term testing (as is done with seasonal flu vaccines every year),” he notes.

And he’s not the only one who thinks so. A new public-private coalition, the Coalition for Epidemic Preparedness Innovations (CEPI), which is backed by the Wellcome Trust and the Bill & Melinda Gates Foundation, was formed in September with the aim of derailing epidemics by speeding up the development of vaccines.

It will take time before the new initiative starts gaining momentum, but in the meantime there are several promising vaccines under development set to make their mark in 2017 and beyond.

Fighting bioterrorism with thermostable vaccine

At Prokarium, work is underway to develop vaccines against both emerging diseases and bioterrorist threats, with the first – an anti-bioterror vaccine against plague – set to start Phase I clinical trials in 2017.

While it is currently a rare disease, plague bacteria are easily cultured and could be made into an aerosol for bioterrorism with less difficulty than other disease-causing organisms. Prokarium’s aim is to create a vaccine that’s not only highly effective against the disease, but also easy to administer and stable for long periods in storage. This way, governments could stockpile it and have ready access to it at short notice.

"Survival of mice is 100% when given two or more doses, and 83% with a single dose."

Early results have been encouraging. “Our oral vaccines are stable at 40°C for 14 weeks and have shelf lives of over 3 years at 4°C – and in terms specific function of our plague vaccine – survival of mice is 100% when given two or more doses, and 83% with a single dose,” Fjällman notes.

“Our preferred outcome is that we can protect humans against plague with a single, oral dose of thermostable vaccine against plague and this is the challenge we face. However, even a two dose vaccine will be very valuable as there is currently no plague vaccine available.”

The project will also serve as a clinical proof-of-concept for Prokarium’s Vaxonella platform, which promises to speed up the development of oral, thermostable vaccines in general.

In other disease areas, Prokarium is developing vaccines against chlamydia, Clostridium difficile, exacerbations of chronic obstructive pulmonary disease (COPD) and asthma, diarrhoea and Zika. The first two will also enter clinical trials at the end of 2017, while the latter three may enter clinical trials in 2018 and beyond. The company is seeking collaborations to develop a combination vaccine against typhoid and paratyphoid, covering both causes of enteric fever, which is a major problem on the Indian subcontinent.

Zika virus vaccines – waiting to move

Researchers at the University of Pittsburgh School of Medicine have developed two vaccines against the Zika virus, which have successfully conveyed immunity from female mice to pups conceived weeks after the mother’s vaccination. With no vaccine, the Zika virus can pass to a pregnant woman’s foetus, which can damage the developing baby and cause severe neurological birth defects, including microcephaly, or an abnormally small head.

One of the vaccines uses a “microneedle array” to deliver the vaccine just below the surface of the skin through tiny crystals that dissolve after being affixed to the skin by a Band-Aid-like patch, while the other uses the traditional needle delivery format and adenovirus – a type of common cold virus – to present Zika antigens to the immune system to induce immunity. Both used proteins on the “envelope” or outer shell of the virus as the antigen to prime the immune system so it can quickly recognise and fight off the actual virus.

Although the adenovirus vaccine performed better in the study, the researchers have stressed that it wouldn’t work well in humans, because the vast majority have already had adenovirus colds, which would result in the immune system simply neutralising the vaccine and failing to develop proper Zika antibodies. The researchers instead decided to move forward with the microneedle array solution, and have since developed a promising, second-generation vaccine.

The problem now, according to Andrea Gambotto, M.D., associate professor of surgery in the School of Medicine and a co-author of the study, is moving to the next step. “In the US, Congress has approved the $1.1 billion bill to provide funding for Zika prevention and research, but we have no idea where the money will go. [If we had funding] we could have already started the second cycle of animal experiments and moved forward very quickly, but the reality is that we can’t because I don’t have the manpower to have 20 people working on something that we’re not sure will be funded. So we’re now waiting to be able to move.”

Universal flu vaccine – asking new questions

An international team of scientists have designed two universal flu vaccines that could protect against the majority of the known viral strains, helping prevent future global pandemics. One can protect against up to 88% of known flu strains worldwide in a single shot, while the other covers 95% of known US influenza strains.

"One can protect against up to 88% of known flu strains worldwide in a single shot."

The team, which includes researchers from Lancaster University, Aston University and the Complutense University of Madrid, used their knowledge of the flu virus and the human immune system, as well as advanced computational techniques, to design the components of a vaccine that gives much broader protection than current options. It is comprised of short flu virus fragments – called epitopes – all of which are already recognised by the immune system.

As Dr Darren Flower of Aston University explained: “Epitope-based vaccines aren’t new, but most reports have no experimental validation. We have turned the problem on its head and only use previously-tested epitopes. This allows us to get the best of both worlds, designing a vaccine with a very high likelihood of success.”

The next step is to find collaborators who might be interested in synthesising and testing the new solutions, according to Lancaster University’s Dr Derek Gatherer. “It’s currently just a designed construct, like an architect’s plan for a new building. It’s difficult to say what the timescale might be for even the initial steps to be carried out,” he notes, adding that there are many challenges to be overcome before the vaccine could reach the stage of human trials.

“We do believe, however, that our vaccine is better than previous universal vaccines for flu, because we’ve taken new information about the human immune system into account. Previous synthetic vaccine design only asked the question, ‘What parts of flu evolve slowest?’ We’ve also asked ‘What makes the human immune system respond strongly?’ The intersection of these two questions is where our design lies.”