It could take years before our immune systems build up defences against the ever-changing virus that causes Covid-19 – but an immunologist is optimistic we'll soon have a much smarter booster to fight it.
Modellers estimate that well over half of the population has now been exposed to the coronavirus, while 2.7 million Kiwis have been boosted – including nearly 250,000 who've received a fourth dose.
For those who received their booster more than three months ago, much of the protection they received against symptomatic disease will have waned substantially – even if the vaccine continued to be a reasonably strong shield against severe sickness.
At the same time, experts say a large proportion of the population would now have "hybrid immunity" from vaccination and natural infection, giving further protection against the worst outcomes of catching Covid-19 again.
"Yes, levels of neutralising antibodies wane over time - but our immune memory from prior vaccination or a previous infection remains," University of Auckland immunologist Associate Professor Nikki Moreland explained.
"This memory includes T-cells, as well as B-cells, that can be activated to fight a new infection.
"Once activated T-cells can recognise eliminate infected cells, while B-cells can start making neutralising antibodies again."
Just how our immunity might keep up with a virus that kept throwing new subvariants at us was a question that scientists were still trying to answer.
That's despite a wealth of longitudinal data and sophisticated analyses putting our understanding of immune memory to the virus ahead of any other acute infectious disease.
Our extensive scientific review of SARS-CoV-2 immune memory is published. Antibodies, CD4 T cells, CD8 T cells, memory B cells, and tissue resident cells. After vaccination, infection, or both, ready to battle COVID-19. Open access: https://t.co/28R4JHja4n @SetteLab pic.twitter.com/QIKzdeez2w— Prof. Shane Crotty (@profshanecrotty) July 15, 2022
In one new US study, researchers turned to a distant cousin of Sars-CoV-2 – common cold coronaviruses.
To fight these familiar foes, we've all built up stable memory responses of antibodies and T cells – presumably from multiple exposures – which has meant infections with them tend to be infrequent and mild.
The study authors, from California-based La Jolla Institute for Immunology, thought this long-term response might also tell us how immunity can build up against Sars-CoV-2 – with boosting needed to top up our cellular armies.
After analysing data gathered before the pandemic, they found adults with stable immune memory tended to catch common cold coronaviruses only about every eight years.
While SARS-CoV-2 was different from these viruses, they did have many structural similarities, and previous work suggested the immune system recognised similarities between different coronaviruses.
The study also showed that antibodies and T cells from its group of adults could cross-react with SARS-CoV-2 – which might also help protect people from severe Covid-19.
If the pattern observed in common cold coronaviruses held true for Sars-CoV-2, there was the possibility reinfections might become less frequent over time, with symptoms less severe.
Although the rise of new Sars-CoV-2 variants might complicate the process of building immunity, there was "certainly reason to assume that eventually this will be the end result; but we are not there yet", lead author Professor Alessandro Sette said.
In the meantime, boosting would remain crucial.
Professor Graham LeGros, an immunologist who heads the Wellington-based Malaghan Institute of Medical Research, agreed – but added we weren't immunologically naïve anymore.
"We're no longer completely susceptible," he said.
"A lot of people are now immunised either by infection or vaccine – and there will be a strong T cell memory that will last a long time."
Another study, published this month in Proceedings of the National Academy of Sciences, found one specific group of protective and highly-specialised T cells could remain 20 months after infection.
Its authors, who analysed more than 80 hospital blood samples in Sweden, said that might explain a reduced risk of severe disease and death being observed among re-infected patients.
"So, I wouldn't think we are going to see the outcomes we were initially terrified of at the very beginning, when we were seeing a large number of deaths in China, Italy and the UK," Le Gros said.
"Still, we don't keep enough immunity to produce a good, neutralising antibody response at the highest level – and we want to achieve better immunity than we have right now."
He pointed out that Sars-CoV-2 has only been circulating among us for a few years – and we hadn't built up the layers of immunity that might help us target different variants as they arose.
The Omicron subvariant that's been fuelling this winter wave – BA.5 - happened to be a master at evading immunity, with modelling suggesting that nearly half of cases in it could be reinfections.
Some studies have also indicated BA.5 might be four times more resistant to antibodies from vaccines than BA.2 - although a second booster remained the best defence for at-risk people eligible for one – and it's likely BA.5 itself will soon be replaced, perhaps by the ascendant BA.2.75.
Beyond that, there was nothing to say we wouldn't see a completely different variant come over the horizon – just as Omicron was to Delta – amid possibilities like zoonotic spill-back or antigenic shift.
"So, I'm afraid the future looks pretty grim for the next couple of years, as we keep seeing these different variants; we're going to be in a washing machine-like situation where our immune systems are constantly mixing and matching over time," Le Gros said.
"In five years' time, however, we might be in pretty good shape."
Moreland was also reluctant to make firm predictions for the future, given "we're still in relatively early days" for understanding long-term immune responses and memory.
"But I do think it's reasonable to speculate that with each successive wave of Covid-19, we should see proportionally less severe outcomes," she said.
"This is because we're building more and more immune memory in the population through vaccination, boosters and infections."
Within a few years, we'd likely also have smarter vaccines.
Le Gros – who's involved in a programme to create a Covid-19 vaccine here in New Zealand, with clinical trials scheduled for early next year – was optimistic we'd soon see a shot that could attack the virus in multiple forms.
Last month, Pfizer and BioNTech announced a new clinical trial for universal vaccine candidates that would include T-cell enhancing and "pan-coronavirus" shots that "protect against the broader family of viruses and its mutations".
"We have to remember our initial vaccines were based on the first structures and proteins made by the first variants of the virus," LeGros said.
"As we come to better understand the roadmap this virus is following to escape our immune protection, we'll be able to understand what its limits are, and design a pretty good vaccine."
Over the longer term, he said it was reasonable to assume we'd need – or at least vulnerable people would – an annual jab, just as we do with influenza.