27 Apr 2020
Pustules, Poxes and World Immunisation Week
Written by Nobel Laureate Professor Peter Doherty
Swiftwater, with less than 1000 people, is a tiny, rural community in the great State of Pennsylvania. It’s also home to one of the world’s biggest influenza vaccine laboratories. When I visited there to give a research seminar many years back, it was owned by the Canadian Company, Connaught. Now, with all the shapeshifting that’s occurred in the pharmaceutical/vaccine industry, it’s part of the global giant, Sanofi Pasteur. Why locate a major vaccine facility in such a remote place? Think cows!
Back in the late 18th century, English physician Edward Jenner realised that milkmaids, who handled cow teats showing the pustules (blisters) of cowpox, had clear complexions unmarked by the terrible, often lethal, human disease variola, or smallpox. Jenner was a variolator. That is, he took pustular material from smallpox sufferers, dried it, then scratched (scarified) the powder into the arms of children. As is the case now for COVID-19, children were much less affected by smallpox. In those days of high childhood mortality, most survived and were protected from smallpox for life. The practice, which began in China and made its way across to the Middle East, was introduced to English doctors by the forceful Lady Mary Wortley Montague, the wife of the British ambassador to Persia.
What Jenner did in 1796 was to take cowpox pustules, scratch the stuff into the arm of young James Phipps, then later challenge him with variola. A modern medical ethics committee would not, of course, allow us to do such an experiment. But it worked, and, the infinitely safer procedure of vaccination replaced variolation. Vacca is the latin word for cow; Jenner’s cowpox vaccine became known as vaccinia and the era of vaccination/immunisation began. A late 19th century engraving shows a calf, tethered in a little tent behind a much larger tent where fashionably dressed Parisians are receiving their vaccine straight from the “skin blisters” on the calf. The Anti-Vaxxers of the day drew cartoons showing people with cow horns growing out of their heads!
Workers at the Pasteur Institute in Paris soon found that vaccinia virus survived well in the presence of glycerine. Bottled vaccine in a doctor’s surgery rapidly replaced the infected calf in the Bois de Boulogne. That’s when, in 1897, Richard Slee, who had married the daughter of the proprietor of the Swiftwater Inn, founded the Pocono Laboratory as the first US “vaccinia-virus-vealer” factory, which later became the Sanofi Pasteur flu vaccine facility. By 1915, Slee’s Swiftwater laboratory was also making typhoid, tetanus and canine distemper vaccines.
In 1980, using a vaccine that was not too different from the product introduced by Jenner, refined by Pasteur and produced by Slee, the World Health Organization (WHO) ended the scourge of smallpox. This is only one of two infections to have ever been eradicated from the planet. The other is the cattle disease, rinderpest.
The Jenner lineage is right there in the current race against time to develop an effective COVID-19 vaccine. Vaccinia is a big virus, with plenty of room for the molecular engineers to stick in bits of other pathogens. In the specialised world of vaccinology, such “vaccinia recombinants” belong to a broader, “virus-vector” family. Large numbers of people participating in AIDS vaccine trials have, for example, been injected with an “attenuated” form of vaccinia (MVA, modified vaccinia Ankara) incorporating components of the causative human immunodeficiency virus (HIV). These trials all failed, partly because (unlike SARS-CoV-2) HIV mutates too much.
The Atlanta-based GeoVax company is using its well-established (for HIV) MVA-VLP “platform” to make a COVID-19 vaccine. The virus-like-particle, or VLP, they’re aiming to deliver in MVA will include non-infectious elements of the SARS-CoV-2 virus that, from previous experience with HIV-MVA constructs, should (after further testing in animals and human volunteers) be safe to inject into us.
The Jenner Institute at the University of Oxford has produced an alternative, virus-vectored COVID-19 vaccine that uses a much smaller (than MVA) adenovirus (Ad). The Ads cause colds in us, though this one is of chimpanzee origin. Following preclinical evaluation in ferrets at CSIRO’s Australian Centre for Disease Preparedness (formerly AAHL), Geelong, the first doses of ChAdOx1 have just gone into human arms. Beyond MVA and Ad, other SARS-CoV-2 VLP vaccine strategies are being researched at our Institute, and elsewhere in Australia. The tried and true VLP approach is the basis of Gardasil, the enormously successful human papilloma virus vaccine developed initially by Ian Frazer and Jian Zhou at the University of Queensland to prevent cervical cancer in women
Vaccination, immunisation, we use the words interchangeably. April 24-30 is World Immunisation Week (WIW). Hopefully, by the time WIW comes around again in 2021, massive numbers of at-risk people will have received one or other (currently 70+ candidates) COVID-19 vaccine. That’s an optimistic scenario and will depend on not running into safety issues. Over the following months, I’ll be writing a lot more about vaccines and immunity. As results start emerging, we’ll discuss promising COVID-19 vaccines and look at their performance out there, on the battle-front.
Artwork: Illustrated by Antra Svarcs for the Metro Tunnel Creative Program (not under Creative Commons license)