What will the future of Covid vaccination look like?

In a week when coronavirus cases have setting alarming new records on an almost daily basis, we continue to be reassured the the vaccines are weakening the link with hospitalisation and death (which they are) and that we have to start "learning to live with the virus" (whether now is the right time given that only half the total population is fully vaccinated is still debatable).

There remains considerable uncertainty about how the pandemic will unfold over the coming weeks, though we would hope to see a slowdown in the infection rate at some point this summer as vaccination coverage increases and - inevitably - more people catch the virus naturally and develop antibodies.

HeraldScotland: Vaccine uptake has been extremely high to date, with more than 98% of all over 60s fully vaccinatedVaccine uptake has been extremely high to date, with more than 98% of all over 60s fully vaccinated

There is talk of booster vaccinations in autumn - but we do not yet know whether these will actually be necessary.

There is a push to vaccinate children and teenagers over the age of 12 as the prospect of herd immunity now looks impossible unless we do - but it may be impossible anyway, and the decision over whether or not to recommend mass immunisation of adolescents is mired in ethical dilemmas when their own risk is so low.

READ MORE: We need to learn to live with Covid-19 - but what does that mean? 

Aside from this though, some good news that may have been missed amid all the focus on surging case numbers.

This week also saw the emergence of optimistic new data on the effectiveness of 'mix and match' vaccination - where someone previously given AstraZeneca gets Pfizer for their second dose, and vice versa - and the possibility that the Pfizer and Moderna vaccines may protect against the infection for years.

HeraldScotland: The push is now on give first doses of vaccine to everyone aged 18 and over in Scotland by July 18 The push is now on give first doses of vaccine to everyone aged 18 and over in Scotland by July 18

The durability of vaccine-induced immunity varies massively by disease: influenza mutates so rapidly that scientists have to develop new formulas every year based on what combination of strains is expected to be most prevalent.

They don't always get it right, and even when they do they only tend to reduce the risk of developing symptomatic flu by around 40 to 60 per cent (compared to upwards of 60% for Covid vaccines against infection).

In comparison, a childhood inoculation against measles such as the MMR jag will confer lifelong protection because the virus which causes measles is essentially rigid - it cannot mutate and evolve in the way that, for example, the SARS-CoV2 virus is doing.

HeraldScotland: No decision has yet been reached on whether the UK will offer vaccinations to all children aged 12 to 17No decision has yet been reached on whether the UK will offer vaccinations to all children aged 12 to 17

A major unanswered question hanging over the current pandemic is, once everyone is vaccinated against Covid, how long will protection endure?

A study published in the journal, Nature, this week has provided an intriguing insight - at least for those given the Pfizer vaccine.

US researchers recruited 41 participants, including eight who had had the coronavirus infection in the past, and gave them all two doses of the Pfizer-BioNTech vaccine.

Blood samples taken at regular intervals up to 15 weeks on from their first dose revealed, as expected, high levels of Covid antibodies - especially in people who had also recovered from the infection.

The more interesting results, however, came from lymph node samples collected from 14 of the participants - none of whom had had prior Covid.

READ MORE: Why the Delta variant has left herd immunity through vaccinations mathematically impossible

What the researchers wanted to investigate were structures known an "germinal centres", which temporarily form inside lymph nodes in response to infections or vaccinations.

These have been compared to "boot camps" for training immune cells, but not much was known about how long they last.

In the Nature study, it turned out that the volunteers given the vaccine only (those with prior infection were excluded) had highly active germinal centres - churning out crucial memory B immune cells - for at least 15 weeks.

Memory B cells are essentially the immune system factory: years after a person has recovered from an infection, if the same virus invades again the memory B cells are there to recognise it and can spring to attention, manufacturing the antibodies needed to mount a resistance.

HeraldScotland:

Based on the duration of activity detected in the germinal centres, the scientists estimate that thousands of memory cells will have been generated - many of which will continue to circulate for years and some of which may even take hold inside the bone marrow, where they would be capable of producing lifelong antibodies on demand.

This is not necessarily the same as lifelong or even years' worth of immunity - but it could be.

It depends on how quickly the virus evolves and how well the memory cells produced can continue to respond to new variants (the Pfizer vaccine still responds to the Delta variant, for example, but the response is weaker than it was against the 'wild type' strain which first emerged in Wuhan) and how much the immune responses elicited varies between vaccine types (Moderna, like Pfizer, is an mRNA vaccine and expected to produce a similar result, but AstraZeneca is a vector-based vaccine so the evidence is less clear).

HeraldScotland: Around two thirds of people fully vaccinated in Scotland have been given AstraZenecaAround two thirds of people fully vaccinated in Scotland have been given AstraZeneca

Booster jags could still be required against new variants if they become overly resistant, and people who are immunosuppressed will probably always need top ups - but the wider population may be better placed to put Covid behind them as far as vaccinations go.

The other surprising piece of research this week suggests that mixing and matching different vaccines could actually boost immunity.

READ MORE: Surge in cases 'a cause for concern' - but no new restrictions for now

This could be important if supplies of one type are constrained and, as virus rates escalate, the rationale for not offering AstraZeneca to under 40s, or even under-30s, weakens.

The Com-COV trial at Oxford University found that over-50s given AstraZeneca followed by Pfizer produced a much stronger antibody response than getting both doses AstraZeneca or Pfizer followed by AstraZeneca. And while both doses Pfizer still generated the strongest antibody response, the AstraZeneca-then-Pfizer combination was best for the T cell response.

This may not alter the UK rollout, but it gives us options and for countries such as Australia where the rollout is low or where stocks are limited, this flexibility may benefit patients as well as planners.