It beat smallpox. So now what else can it do?

Genetically altered, the anti-smallpox virus vaccinia can fight many other diseases, writes Bernard Dixon

Is smallpox vaccine due for a comeback? It may seem perverse to ask such a question in 1996. This is the 200th anniversary of Edward Jenner's successful vaccination of young James Phipps, which led to the widespread adoption of Jenner's method of preventing smallpox by infecting people with the related cowpox virus (vaccinia). Two centuries later, having eradicated smallpox using Jenner's technique, the World Health Organisation has announced that the two remaining laboratory stocks of the virus are to be destroyed.

With smallpox gone, there might seem to be little further use for vaccinia. But many other viruses continue to cause disease and death on a vast scale throughout the world. And one means of combating them may be to use genetically altered forms of vaccinia.

One expert who believes so is Enzo Paoletti. More than 10 years ago he discovered how to insert genes from other microbes into the DNA of vaccinia. In principle, if such an inserted gene normally produces a particular protein in the donor microbe, then it could do so in the cells of its new host too. And if that protein, in its original place, induced an infected animal to produce antibodies, the augmented vaccinia virus might do the same thing.

It worked. Scientists have since engineered several such "recombinant vaccines". One is a version of vaccinia designed to provoke immunity against rabies when taken by mouth. It has been distributed in several parts of Western Europe, injected into chicken heads left to be eaten by wild foxes, which can carry rabies. Many foxes took the bait and the disease is virtually extinct in Belgium.

Although such vaccines appear to be safe, scientists remain cautious about the prospects of using similar ones in humans, or in animals in contact with humans. First, the procedure is not trouble-free. At the injection site, vaccinia can cause unpleasant reactions, which are likely to be severe in individuals whose immune systems are impaired - by Aids, for example, or by drugs given to prevent the rejection of transplanted organs. Second, it is theoretically possible that a genetically altered vaccinia virus could pass from humans to wildlife, or interact with related viruses, with uncertain consequences.

Paoletti believes that an alternative approach may prove more acceptable and equally effective: to use viruses that have the advantages of the first generation of recombinant vaccines, but none of their disadvantages. Several are being developed which have virtually no side-effects, provoke immunity and, like conventional vaccinia, are "live"; they do not reproduce (or do so poorly) in recipients' cells and so cannot spread to other animals.

As a basis for one range of vaccines, Paoletti and colleagues have removed several regions of DNA from vaccinia that it require to multiply harmfully. Known as NYVAC, the resulting virus retains the capacity to grow normally in chick embryo cells, yet can scarcely grow at all in human and other animal cells. NYVAC does not produce inflammation at the injection site, and has negligible ill-effects, even in mice whose immune systems have been compromised. When researchers incorporated into NYVAC relevant genes taken from Japanese encephalitis virus and equine influenza virus, the resulting vaccines protected pigs and horses respectively against these infections.

Another strategy, pioneered by the Virogenetics Corporation, focuses on vaccinia-related viruses that normally infect birds. These too can be genetically altered so that they immunise various mammals against other microbes, even though the viruses do not multiply in mammalian cells. A modified canarypox virus, for example, has protected dogs and cats experimentally against rabies.

A recently recognised use for recombinant poxviruses is in cancer treatment. Many types of tumour cell have on their surface antigens - proteins characteristic of those tumours - which can induce the body to make antibodies. Unfortunately, the response of the immune system to such antigens is normally weak or non-existent. However, a poxvirus carrying not only a tumour antigen but also a cytokine (a natural substance that heightens the immune response) might provoke the production of sufficient antibody to attack a patient's tumour.

PROMOTED VIDEO
News
REX/Eye Candy
science
News
A photo of Charles Belk being detained by police on Friday 22 August
news
News
i100
Sport
Alexis Sanchez celebrates after scoring his first goal for Arsenal in the Champions League qualifier against Besiktas
sportChilean's first goal for the club secures place in draw for Champions League group stages
Arts and Entertainment
Amis: 'The racial situation in the US is as bad as it’s been since the Civil War'
booksAuthor says he might come back across Atlantic after all
Extras
indybest
News
ebooksAn evocation of the conflict through the eyes of those who lived through it
Life and Style
Google Doodle celebrates the 200th birthday of Irish writer Sheridan Le Fanu
tech
Arts and Entertainment
Vinyl demand: a factory making the old-style discs
musicManufacturers are struggling to keep up with the resurgence in vinyl
News
i100
News
In Eternal Sunshine of the Spotless Mind Jim Carrey and Kate Winslett medically erase each other from their memories
scienceTechnique successfully used to ‘reverse’ bad memories in rodents could be used on trauma victims
Arts and Entertainment
Singer Pixie Lott will take part in Strictly Come Dancing 2014, the BBC has confirmed
tv
Independent
Travel Shop
the manor
Up to 70% off luxury travel
on city breaks Find out more
santorini
Up to 70% off luxury travel
on chic beach resorts Find out more
sardina foodie
Up to 70% off luxury travel
on country retreats Find out more
Latest stories from i100
Have you tried new the Independent Digital Edition apps?
Independent Dating
and  

By clicking 'Search' you
are agreeing to our
Terms of Use.

iJobs Job Widget
iJobs General

C# Developer (C#, ASP.NET Developer, SQL, MVC, WPF, Real-Time F

£40000 - £48000 per annum + benefits+bonus+package: Harrington Starr: C# Devel...

C# Swift Payment Developer (C#, ASP.NET, .NET, MVC, Authorize.N

£45000 - £60000 per annum + benefits+bonus+package: Harrington Starr: C# Swift...

Front-End Developer (JavaScript, HTML5, CSS3, C#, GUI)

£55000 - £70000 per annum + Benefits + Bonus: Harrington Starr: Front-End Deve...

Graduate C# Developer (.NET, WPF, SQL, Agile, C++) - London

£30000 - £40000 per annum + Benefits + Bonus: Harrington Starr: Graduate C# De...

Day In a Page

Israel-Gaza conflict: No victory for Israel despite weeks of death and devastation

Robert Fisk: No victory for Israel despite weeks of devastation

Palestinians have won: they are still in Gaza, and Hamas is still there
Mary Beard writes character reference for Twitter troll who called her a 'slut'

Unlikely friends: Mary Beard and the troll who called her a ‘filthy old slut’

The Cambridge University classicist even wrote the student a character reference
America’s new apartheid: Prosperous white districts are choosing to break away from black cities and go it alone

America’s new apartheid

Prosperous white districts are choosing to break away from black cities and go it alone
Amazon is buying Twitch for £600m - but why do people want to watch others playing Xbox?

What is the appeal of Twitch?

Amazon is buying the video-game-themed online streaming site for £600m - but why do people want to watch others playing Xbox?
Tip-tapping typewriters, ripe pongs and slides in the office: Bosses are inventing surprising ways of making us work harder

How bosses are making us work harder

As it is revealed that one newspaper office pumps out the sound of typewriters to increase productivity, Gillian Orr explores the other devices designed to motivate staff
Manufacturers are struggling to keep up with the resurgence in vinyl records

Hard pressed: Resurgence in vinyl records

As the resurgence in vinyl records continues, manufacturers and their outdated machinery are struggling to keep up with the demand
Tony Jordan: 'I turned down the chance to research Charles Dickens for a TV series nine times ... then I found a kindred spirit'

A tale of two writers

Offered the chance to research Charles Dickens for a TV series, Tony Jordan turned it down. Nine times. The man behind EastEnders and Life on Mars didn’t feel right for the job. Finally, he gave in - and found an unexpected kindred spirit
Could a later start to the school day be the most useful educational reform of all?

Should pupils get a lie in?

Doctors want a later start to the school day so that pupils can sleep later. Not because teenagers are lazy, explains Simon Usborne - it's all down to their circadian rhythms
Prepare for Jewish jokes – as Jewish comedians get their own festival

Prepare for Jewish jokes...

... as Jewish comedians get their own festival
SJ Watson: 'I still can't quite believe that Before I Go to Sleep started in my head'

A dream come true for SJ Watson

Watson was working part time in the NHS when his debut novel, Before I Go to Sleep, became a bestseller. Now it's a Hollywood movie, too. Here he recalls the whirlwind journey from children’s ward to A-list film set
10 best cycling bags for commuters

10 best cycling bags for commuters

Gear up for next week’s National Cycle to Work day with one of these practical backpacks and messenger bags
Paul Scholes: Three at the back isn’t working yet but given time I’m hopeful Louis van Gaal can rebuild Manchester United

Paul Scholes column

Three at the back isn’t working yet but given time I’m hopeful Louis van Gaal can rebuild Manchester United
Kate Bush, Hammersmith Apollo music review: A preamble, then a coup de théâtre - and suddenly the long wait felt worth it

Kate Bush shows a voice untroubled by time

A preamble, then a coup de théâtre - and suddenly the long wait felt worth it
Robot sheepdog technology could be used to save people from burning buildings

The science of herding is cracked

Mathematical model would allow robots to be programmed to control crowds and save people from burning buildings
Tyrant: Is the world ready for a Middle Eastern 'Dallas'?

This tyrant doesn’t rule

It’s billed as a Middle Eastern ‘Dallas’, so why does Fox’s new drama have a white British star?