The long road to a Covid-19 vaccine | Free to read

It was hailed as a breakthrough vaccine for dengue fever, a neglected tropical disease that kills about 20,000 people each year. Dengvaxia, made by Sanofi Pasteur, was being rolled out to more than 800,000 schoolchildren in the Philippines when reports began trickling in of vaccinated children falling seriously ill, and some dying.

The 2017 rollout was halted; the country’s health minister, along with other officials and six Sanofi employees now await trial on charges of “reckless imprudence resulting in homicide”.

All the accused deny the charges and the company insists the vaccine is safe. But there remains an unresolved scientific mystery at the heart of the Dengvaxia tragedy: in a small subset of people, can a vaccine make an infection worse rather than better?

That question has never been more apposite. A post-coronavirus world depends on a Covid-19 vaccine. Without it, a return to normality carries the peril of more deaths from a novel respiratory virus to which humans carry no prior immunity and for which there are no life-saving treatments.

One drug authorised for treating Covid-19 patients, remdesivir, is not a game changer: it shortens recovery time but does not boost survival chances.

But a shadow looms over the global race to develop a pandemic vaccine: a little-known phenomenon called antibody-dependent enhancement (ADE), also known as disease enhancement or immune enhancement.

This series of photographs taken in 1962 shows scientists working on the polio vaccine in the research laboratory of the Pasteur Institute in Paris © Keystone-France/Gamma-Keystone/Getty Images

It refers to a counter-intuitive and potentially dangerous situation: when the presence of antibodies, which are supposed to vanquish disease, worsens rather than quells an infection.

It is a rare but not idle concern. The pandemic virus belongs to the same family of coronaviruses that causes Sars (severe acute respiratory syndrome) and Mers (Middle East respiratory syndrome). The hunt for vaccines for these 21st-century diseases — Sars appeared in 2002, Mers in 2012 — has been stymied by evidence of ADE.

Some animals that were given experimental Sars vaccines suffered more severe lung inflammation than unvaccinated animals when subsequently infected. Those trials stopped and there is still no effective Sars vaccine.

Beate Kampmann, director of the Vaccine Centre at the London School of Hygiene & Tropical Medicine (LSHTM), says that observations of ADE with previous coronaviruses mean vaccinologists must tread carefully. “We don’t want to blow the risks out of proportion but nobody can give a 100 per cent guarantee that disease enhancement won’t happen. If it does emerge here, it would be a very serious challenge.”

The emergence of ADE would be a setback for any candidate vaccine — and a cruel plot twist in the tale of Covid-19, which has turned out to be a more disruptive contagion than either Sars or Mers.

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