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* More companies join Zika vaccine development race
* Safe shot for at-risk women and girls a big challenge
* Full regulatory approval of vaccine will take years
* Commercial opportunity for Zika vaccine uncertain
By Kate Kelland and Ben Hirschler
LONDON, Feb 2 (Reuters) - The world is once again asking
scientists and drugmakers to come up rapidly with a vaccine for
a viral disease that, in the latest case, few people had heard
of until a few weeks ago, and even fewer feared.
Making a shot to generate an immune response against Zika
virus, which is sweeping through the Americas, shouldn't be too
hard in theory. However, producing a safe, effective and
deliverable product to protect women and girls who are at risk
is not easy in practice.
For a start, scientists around the world know even less
about Zika than they did about the Ebola virus that caused an
unprecedented epidemic in West Africa last year.
Ebola, due to its deadly power, was the subject of
bioterrorism research, giving at least a base for speeding up
vaccine work. This time, the knowledge gap is more daunting.
There are just 30 mentions of Zika in patents, against 1,043
for Ebola and 2,551 for dengue fever, according to Thomson
Reuters Derwent World Patents Index. And there have been only
108 high-profile academic papers on Zika since 2001, against
more than 4,000 on Ebola, as found in the Web of Science.
Still, the U.S. National Institutes of Health, the Public
Health Agency of Canada and the Butantan Institute in Brazil
have started work on potential candidates for a Zika vaccine,
and several biotech firms are in the race.
They include NewLink Genetics NLNK.O , which helped develop
the first successful Ebola vaccine with Merck (N:MRK) & Co MRK.N .
Importantly, there is now a "big gun" vaccine maker with
skin in the game: Sanofi SASY.PA said on Tuesday it will
launch a Zika vaccine programme, a day after the World Health
Organization declared the disease and its suspected links to
birth defects an international health emergency.
Canadian researcher Gary Kobinger told Reuters he believes
an experimental Zika shot might be able to be used on a limited
emergency basis as soon as late 2016, although full regulatory
approval will take years.
Ben Neuman, an expert on viruses at Britain's University of
Reading, says there are many hurdles ahead. "To be useful, a
Zika vaccine would need to be effective and safe, but it's
difficult to do both," he told Reuters. "It's a balancing act."
That's because a good vaccine works by provoking the immune
system into a strong response - but not enough to make a person
sick - and there is no simple way to assess the right immune
response for Zika, according to one drug company expert.
Zika infection is so mild in the vast majority of cases that
its victims are unaware they are even infected, so this group of
potential patients is unlikely to need or want immunisation.
The crucial target group is women who may be pregnant, since
the disease's greatest suspected threat is the possible link to
severe birth defects.
CLINICAL TRIALS
All of this makes developing and testing a vaccine highly
complex, especially since pregnant women are often excluded from
clinical trials until the safety of new drugs or vaccines is
well-established in other population groups.
It also makes for an uncertain and potentially limited
market for any Zika vaccine.
Assuming Sanofi or another company succeeds in developing
one, the vaccine may be used only in teenage girls - protecting
them before they are likely to become pregnant - in countries
and regions where Zika-carrying mosquitoes thrive.
"It's a public health good initiative, it's not necessarily
a commercial initiative," said Berenberg Bank analyst Alistair
Campbell. "Zika is something that has cropped up suddenly and
may well dissipate, so there may not be a sustainable annual
cohort of patients for vaccination."
Still, the WHO and other public health authorities will be
relieved that one of the world's top drugmakers has pledged to
work on a vaccine.
GlaxoSmithKline GSK.L is also investigating Zika and a
spokeswoman reiterated on Tuesday it is concluding feasibility
studies to see if its vaccine technology might be suitable.
Ultimately, developing vaccines is a question of priorities,
as evidenced by a patchy pattern of protection against a range
of mosquito-borne viruses over the past 80 years.
There was early success with the development in 1938 of the
first vaccine against yellow fever, which belongs to the same
virus family as Zika. More recently, drugmakers have
successfully developed shots against Japanese encephalitis and
dengue.
The first dengue vaccine, from Sanofi, was approved in
December - after 20 years' work.
Work on other mosquito-borne diseases such as West Nile
fever and chikungunya is still underway.
One idea for tackling Zika is to adapt vaccine prototypes
for dengue and West Nile, using them as a "platform" for the
Zika virus. But even this approach would not be simple.
"For most viruses, there are lots of ways to make a somewhat
effective vaccine, but the most effective vaccines target
several parts of the virus in different ways," said Neuman.
Multiple targets give the immune system more options,
meaning more people are able to develop immunity. Yet an
effective vaccine in most people may pack too much punch for
others, with the potential to trigger birth defects.
"It's big concern," Neuman said. "And at this stage we just
don't know."
(editing by David Stamp)