Scientists don’t think Covid mutations have yet presented us with “immune escape”

Whilst working on tweaks to their vaccines, Pfizer and Oxford scientists don’t think the new Covid mutations have yet presented us with an “immune escape” problem.

Interesting observations from the experience and evidence from Mers and Birdflu vaccines were presented in a Sunday Times article.

Extract from Ben Spencer, Science Editor www.thetimes.co.uk

Towards a second-generation vaccine

Pfizer is working on the prototype of a tweaked vaccine to see off this threat [from covid mutations]. In Oxford, Professor Sarah Gilbert, principal investigator of the group that developed the AstraZeneca vaccine, is also developing a new formulation.

Her team is confident that a modified version will be ready by the autumn — an incredible feat in normal times. For many, however, even that is not fast enough. “We are getting a lot of hate mail from people saying, ‘Why are you going to take so long to make a new vaccine?’” Gilbert said.

Neither Gilbert nor Dormitzer (Philip Dormitzer, the chief scientific officer of Pfizer’s viral vaccines divisioni) is convinced that an adjusted vaccine is necessary. Studies suggest that the South African B.1.351 variant, in particular, reduces the ability of vaccines to ward off mild disease. But there are indications that they still provide enough immunity to prevent hospitalisation and death, the main task of the vaccines.

Pfizer and Oxford are working on prototypes of tweaked vaccines in case these are needed later in the year. The Oxford team has started sequencing the genetic code of several mutated spike proteins, which will be inserted into cells to create a seed stock. “From that master virus seed stock all the batches can be created,” Gilbert said.

Dormitzer is working on a similar process. “I don’t think we are seeing immune escape quite yet — but we may see a strain in the future that does,” he said. “We must be prepared for the worst because the consequences of not doing so are too great. So that is what we are doing. And the best way is to make a small batch and take it to the point of a clinical trial.”

Boosters

Boris Johnson told the Commons last week that people were “going to have to get used to the idea” of vaccinating and revaccinating. Repeated boosters might be needed for two reasons. The first is to provide a top-up, perhaps every year or two, if immunity wanes. The second is to deal with variants. If a virus changes year to year, vaccines need to keep up. That is the case with flu, which mutates far more quickly than any coronavirus.

In fact scientists are confident that boosters will not be needed — for either reason. A third dose may well be required this year to cope with the new strains, and is likely to be given to elderly and vulnerable people in the autumn. But Dormitzer said that a third dose of the same strain could provide enough immunity to get around even a particularly troublesome new strain after that.

Before he joined Pfizer, he led the viral vaccines team at Novartis and spent several years developing immunisations against pandemic influenza. There he learnt that the spacing of doses can help produce lasting immunity.

Vaccines against H5N1 bird flu, which spread throughout the world from 2005, generated an extraordinary immune response if two doses were given a few weeks apart, followed by a third some months later. The result was immunity against five strains of the virus.

“It gave not only very strong immunity but very broad immunity,” Dormitzer said. “You didn’t have to change the strain and the response you got was terrific. Now, that doesn’t mean that would be true for Sars-Cov-2. We have to test that hypothesis.”

Gilbert, too, is confident of the staying power of immunity. She points to a study her team did on Mers, another coronavirus, in which a single vaccine provided stable protection. They found that antibody and T-cell levels dropped for the first six months, then hit a plateau. “And then it just stays at that level,” she said. “They didn’t really change after a year — and that’s just with one vaccination. So I would predict that having given two vaccinations 12 weeks apart, it will look even better. The plateau will be at a higher level.”

A childhood vaccination programme?

The possibility of stable immunity offers a tantalising prospect for Dormitzer. “If we have very long-lasting immunity then the question is, could this become a childhood or infant vaccine?” he said.

It could mean children are vaccinated early and protected for much of their lives. Anyone exposed to the virus as an adult may suffer a mild illness — but that would merely serve to boost immunity. “If they get infected, it won’t be very serious — it will just be a sniffle,” Gilbert said.

As people age, and the consequences of infection become more serious, it might be necessary to vaccinate again, potentially more than once. The prize is lifelong freedom from fear of the virus and the restrictions and sacrifices that it once brought.

Pfizer and Oxford are taking the first steps towards such a programme. Both teams are set to begin trials of their vaccines on children this spring. Oxford is starting with teenagers and working down the age groups, while Pfizer is vaccinating children aged 5 to 11, having already vaccinated the 12-15 age group as part of the original adult trial.

Professor Adam Finn, deputy chairman of the joint committee on vaccination and immunisation, which advises the government, has said the results will come in by the autumn. In his view the Medicines and Healthcare Products Regulatory Agency is unlikely to demand a similar quantity of data to that required for the adult trials.

“We need to know we’re giving the right dose to younger children,” Finn told the BBC’s Today programme. “We need to know they’re safe — and that information needs to come in before we start using them. I think we will see vaccines being used in children later in the year.”

Further developments

Vaccine developers are also due to start trials among pregnant women. None of the existing vaccines is licensed for pregnancy, because mothers-to-be were not included in the initial trials.

Women who are at high risk from Covid-19, such as medical staff and those with certain health conditions, therefore face a difficult choice: take an unlicensed vaccine and risk harm to their baby, or face catching the virus, which could also harm the foetus.

Both Pfizer and Oxford have since their initial trials completed developmental and reproductive toxicity studies, which check whether the vaccines might affect the development of a baby in the womb. This means that the two companies have the all-clear to carry out clinical trials among pregnant women.

Pfizer is also working on trials to make its vaccine easier to distribute. At the moment storage at minus 70C necessitates a cold chain, which poses immense logistical challenges.

The Pfizer team has started work on a freeze-dried version, which could be stored in a normal fridge. If this lyophilisation process is successful, the powder version could be ready for distribution early next year — and many more people would be able to receive the vaccine.

“We’re looking to improve the storage and distribution conditions,” said Dormitzer. “I look forward to the day we don’t have to put our vaccines in dry ice,” he said. “But, for now, it is working.”