Manuela Callari
As vaccines rolled out early this year, COVID-19 cases began to dwindle in some countries – fomenting hopes that this pandemic was under control. But with Delta infections surging in highly vaccinated countries such as Israel and the United Kingdom, and an increasing number of “breakthrough” infections, that initial excitement that vaccine could also repress transmission in vaccinated people has all but disappeared.
Although data still show the vaccines are highly effective at preventing severe disease and death, many countries, including the United States, Israel and some parts of Europe, have made the controversial announcement that they will soon offer booster shots to their populations.
Antibody levels will fall over time, but the pool of memory cells left behind will be larger than before, leading to a faster, more robust response to future exposure.
In the meantime, the virus is running rampant in countries where most people are yet to receive even their first dose of the vaccine. Not only does that mean people in poorer countries are suffering and dying at much higher rates, but it increases the risk of new, more highly infectious variants emerging.
Do COVID-19 vaccines lose efficacy over time, or is Delta the culprit in breakthrough infections? Are we still protected long-term from severe disease, or are we all going to need boosters soon? Cosmos looked at the evidence we have so far.
How do booster shots work?
The first dose of a COVID-19 vaccine induces immune cells to produce neutralising antibodies, which then slowly drop over time. This initial response leaves behind a small pool of long-lasting memory B and T cells, which patrol the body for future infections and are ready to act if we are exposed to SARS-CoV2.
When we receive the second dose or booster, antibody-making immune cells multiply, elevating the levels of antibodies once more. Antibody levels will fall again over time, but the pool of memory cells left behind will be larger than before, leading to a faster, more robust response to future exposure.
Boosters also promote a process called affinity maturation. B cells travel to the lymph nodes, where they gain mutations that lead to the production of antibodies able to bind more strongly to the virus.
That decline in antibody levels over time is expected, says Professor Kanta Subbarao, an infectious disease expert and director of the WHO Collaborating Centre for Reference and Research on Influenza. It happens in people who have recovered from COVID-19; it happens with other vaccines; it happens with other infections, she says.
With each booster, antibody levels rise, and the pool of memory cells becomes larger. But eventually, the numbers of memory cells and antibody levels plateau with repeated boosting or reinfection.
Waning immunity or Delta breakthrough?
Many countries with high rates of vaccination are experiencing a surge in cases, with many infections reported among fully vaccinated people. Scientists fear that immunity from COVID-19 vaccines might be fading away over time, leaving vaccinated people increasingly vulnerable to the infection.
The easiest way to measure vaccine effectiveness is to look at antibody levels. The evidence suggests that, as with many other vaccines, antibody levels triggered by most COVID-19 vaccines fade too. What scientists don’t yet know is whether this drop reflects a decline in protection against the virus.
Researchers in Australia have found that neutralising antibody levels are highly predictive of protection against symptomatic infection.
Neutralising antibodies represent our first line of defence in preventing infection, says Professor Gilda Tachedjian, a virologist at the Burnet Institute and president of the Australian Virology Society. But the immune system has other cards to play to protect us from pathogens.
There might also be another reason why more vaccinated people are contracting COVID-19: the Delta variant.
When the virus breaks through the antibody defence and begins replicating into our cells, the pool of memory cells is soon alerted. B-cells begin producing more antibodies, and killer T-cells neutralise those cells that the virus has hijacked. Unlike the antibody response, this mechanism takes a few days to kick in but it protects us from becoming severely ill.
“The good news is that the vaccines we have are inducing very long-lasting immunity at the cellular level,” says Subbarao. “The blood tests that tell you that the antibody levels are declining doesn’t necessarily translate to no effectiveness.
“If you’re walking around with a high level of antibodies, then you’re probably protected from infection. If your antibodies are low and you do get infected, then your memory cells are recalled, they proliferate and prevent severe illness,” she says.
Another Australian study, posted this week as a pre-print, found that mRNA vaccines induce a robust and durable immune memory to SARS-CoV2. The researchers recruited people who had not been exposed to the virus and received an mRNA vaccine, and people who recovered from COVID-19 and received an mRNA vaccine. They measured both antibody and cellular immune responses before vaccination and six months post-vaccination.
They found that while antibody levels declined from peak levels soon after vaccination, they remained detectable in all participants six months down the track. Most importantly, most memory B cells induced by mRNA vaccines were still effective against variants of concern, even more so than memory B cells generated in individuals who recovered from mild infection. Also, mRNA vaccines generated durable, antigen-specific T cells.
There might also be another reason why more vaccinated people are contracting COVID-19. There are indications that current COVID-19 vaccines might be less effective against the new Delta variant.
In a report on nursing home residents across the United States, released by the Centers for Disease Control and Prevention last week, researchers found that the efficacy against all infections of the mRNA vaccines went from 75% pre-Delta to 53% post-Delta.
In a large study recently released as a preprint, researchers from the United Kingdom looked at data from more than 300,000 randomly selected people across the UK obtained through the Office for National Statistics COVID-19 Infection Survey.
“If you define protection as preventing severe illness and death, the protection still very good. If you define protection as preventing all infections, there’s been a bit of a decline.”
The researchers compared the numbers of fully vaccinated and unvaccinated participants who tested positive for COVID-19 during two time periods: December 2020 until 16 May (when the Alpha variant was predominant) and 17 May to 1 August (when Delta was dominant). They found that for both the Pfizer and the AstraZeneca vaccine, protection against symptomatic infection decreased with the arrival of the Delta variant.
Professor Anthony Cunningham, an infectious diseases physician and clinical virologist at the University of Sydney, says antibodies lock to the SARS-CoV2 spike protein, preventing it from latching onto the ACE2 receptors on our cells. While the antibodies triggered by current COVID-19 vaccines might fit well with the spike protein of the original virus strain, he says they might not fit as well to the Delta spike.
The Delta variant is also more infectious than previous strains. That, coupled with reduced antibody levels, says Cunningham, might explain why Delta is more capable of breaking through our first line of defence.
“The reactivity of the antibodies is a little diminished to the Delta variant,” agrees Subbarao. “And that becomes more striking as the antibody levels decline.”
Are we still protected from severe disease?
From the trial and real-world data, it is clear that protection against hospitalisation and severe disease remains high even amid the Delta wave.
When Alpha emerged, vaccines still offered a very good protection, says Subbarao. A study from Israel reported that of 152 breakthrough infections that required hospitalisation during the Alpha wave, 40% of cases were immunocompromised, and 96% had comorbidities. These numbers indicate that serious infections from Alpha in fully vaccinated people without underlying conditions were exceedingly rare.
“That’s changed a little bit with the Delta,” says Subbarao.
But she points out that it is crucial to define what vaccine protection means. “If you define protection as preventing severe illness and death, the protection still very good. If you define protection as preventing all infections, there’s been a bit of a decline.”
She says we need to change our expectations of the vaccines – they are still doing what they were designed for but they might not stop transmission as we have hoped.
We keep forgetting this is a global pandemic
In the future, booster shots might be necessary, particularly for those most vulnerable or immunocompromised. But right now, there is not sufficient evidence to support the decision some of the wealthier countries have taken to offer booster shots to everyone, while poorer countries are still waiting to roll out first doses.
As long as the virus spreads rapidly in certain areas of the world, the risk of new variants of concern emerging looms. That is why the World Health Organization has called for a moratorium on booster shots.
“It’s a real tension between policy makers making policy for their own citizens, and people that have the global view,” says Subbarao. “We need vaccine uptake, but we need that vaccine uptake globally.”