COVID-19 vaccine boosters may protect against future animal coronavirus outbreaks
· News-MedicalCOVID-19 vaccine boosters not only protect against SARS‑CoV‑2 – the virus behind the most recent pandemic – but may also help protect against some future coronaviruses that risk spreading from animals to humans, Cambridge researchers have shown.
In a related study, the team has shown that an individual's first exposure to SARS‑CoV‑2 'locks in' their immune response, impeding their ability to respond to future variants, even when vaccinated.
When an individual is infected with a virus, the immune system produces antibodies that will recognise the virus if it re-enters the body and prevent infection taking hold again. Vaccination works on the same principle.
A team led by scientists in the Gupta and Rihn laboratories at the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), University of Cambridge, asked whether the vaccines currently given against COVID-19 might also protect us against future coronaviruses that risk 'spilling over' from animals to humans.
In findings published today in the journal npj Vaccines, the team studied blood samples from older UK adults (average age around 69) who had received four COVID‑19 vaccine doses, including a recent bivalent booster that included both the original Wuhan strain and the Omicron variant.
They tested how well antibodies in these blood samples could neutralize different Omicron variants of SARS‑CoV‑2. They also tested the antibodies to see if they could neutralize the SARS‑CoV‑1 virus – responsible for the 2003 SARS outbreak – and a range of closely-related coronaviruses (known as 'sarbecoviruses') found in bats and pangolins, some of which are considered potential threats for future outbreaks.
As expected, antibodies worked less well against newer Omicron variants than against the original Wuhan strain, showing how the virus has evolved to escape the immune response. The antibodies were poor at neutralising SARS‑CoV‑1, which is genetically more distant.
Surprisingly, the antibodies were much better at neutralizing two sarbecoviruses closely related to SARS‑CoV‑2 – one from bats and one from pangolins – than they were at neutralising the original Wuhan strain itself, even though these two viruses have never infected humans. Several of the bat and pangolin viruses tested have the ability to enter human cells and are genetically close enough to SARS‑CoV‑2 to raise concern about future spillovers.
Grace West from CITIID, study's joint first authorWe'd expect the COVID vaccine to offer protection against today's variants, but we were surprised to find that it also provides protection against some animal coronaviruses with future pandemic potential."
Rebecca Morse, also a joint first author from CITIID, said: "We may already have a head start when it comes to protecting against certain future outbreaks. Boosters could reduce both severity and spread if spillover were to occur, buying us vital time while we develop a more targeted vaccine. This will be particularly important for older and vulnerable populations, who are usually hardest hit in new pandemics."
The researchers say their findings could inform next‑generation vaccine design. Vaccines that target parts of the coronavirus spike protein common to multiple viruses could protect against related viruses. The spike protein is a key element of the virus that the immune system recognises.
The research was funded by Wellcome and the Medical Research Council, with additional support from the Hong Kong Jockey Club, National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre and Addenbrooke's Charitable Trust.
Why 'first impressions' matter when it comes to COVID-19 immunity
In a second study, Professor Ravindra Gupta and colleagues showed how your first encounter with COVID-19 – either through infection or vaccination – leaves a lasting immune 'fingerprint' that shapes how you respond to new variants for years, with important implications for vaccine design and pandemic preparedness.
Early on in the pandemic, relatively low reported case numbers in many African countries led to the perception that these countries had experienced limited exposure to SARS-CoV-2. But when the team analysed blood samples from unvaccinated adults in Nigeria in early 2023, they found that this was not the case – most individuals had already been exposed to the virus, often more than once, despite many never having been diagnosed or reporting illness.
This presented the team with a rare opportunity to understand how immunity builds up when infection comes first, rather than vaccination. Their findings are published in the journal iScience.
Using two independent cohorts sampled in 2023 while Omicron was circulating, the team found that immune responses were still dominated by earlier strains of the virus, even after subsequent infection with Omicron. This reflects a phenomenon known as 'immune imprinting', where the first exposure to the virus – whether through infection or vaccination – largely determines how the immune system will respond in future. Even after vaccination against or infection by subsequent variants, the immune system still responds as if the virus had not changed since that first exposure, increasing the chances that the virus will 'escape' the immune response.
First author Dr Adam Abdullahi from CITIID, Cambridge, and the Institute of Human Virology, Abuja, Nigeria, said: "The immune system doesn't reset with each new variant. Instead, it builds on its first encounter, and that memory continues to influence how it responds to new variants. It's like how, when we have a negative encounter with someone the first time we meet, this first impression can be hard to shake and informs how we deal with them each time we meet."
To investigate this further, the team removed antibodies targeting earlier strains from the blood samples. With these antibodies removed, the blood was much less able to neutralise either the earlier variants of COVID-19 or Omicron, confirming that responses to newer variants were largely built on pre-existing immune memory.
Although vaccination increased overall antibody levels, it appeared to amplify existing immune memory, boosting responses shaped by earlier infections rather than generating strong new responses to variants such as Omicron. Even after further exposure to Omicron, antibody responses rarely became stronger against this variant than against the original virus.
In other words, immune responses, established during early infection, can persist over time, constraining the body's ability to mount new responses to new variants, even after vaccination or re-exposure.
This suggests that in populations with high levels of prior infection, vaccine performance is partly determined by the sequence of exposures individuals have experienced, including whether infection occurred before vaccination, and which variants were encountered first. The findings may help explain why new variants keep spreading, even in populations with high prior exposure
Ravindra Gupta, The Hong Kong Jockey Club Professor of Global Health at CITIID, University of Cambridge, said: "Vaccines are still extremely important as they help reduce the severity of infection, so it's important to get your boosters if you are vulnerable. But our findings help explain why we see different patterns of immunity across the world. The pandemic did not unfold uniformly, and our vaccination strategies need to reflect that reality.
"Early infection leaves a lasting imprint on the immune system, and in this context, we need to look at designing vaccines that work across different immune histories to help prepare for future pandemics."
Professor Alash'le Abimiku from the Institute of Human Virology, Nigeria, joint lead author, said: "Understanding how populations were exposed to the virus is essential for designing effective vaccination strategies, particularly in settings where infection occurred before vaccine rollout. Future vaccines may need to be designed so they don't just 'replay' the immune system's past experiences, but instead actively train it to recognise and respond well to new variants."
Imprinting may also explain why the COVID vaccine offers greater protection against some sarbecoviruses than it does later variants of SARS-CoV-2, such as Omicron, as reported in the npj Vaccines study.
The original vaccine, like an infection during early COVID-19 waves, caused imprinting of our antibodies against the Wuhan strain, and as the virus mutated over time, the immune system would be increasingly less likely to recognise it. However, some of the bat and pangolin coronaviruses have spike proteins that are more similar to that of the Wuhan strain of SARS-CoV-2 than the spike proteins of Omicron and subsequent variants.
Professor Gupta, who leads The HKJC Global Health Institute, added: "This work was only possible because of close collaboration between Nigerian institutions and international partners, each bringing its own expertise. These partnerships are critical to ensuring that globally relevant evidence is generated from, and directly benefits, populations most affected by emerging infectious diseases."
The research was funded by The Hong Kong Jockey Club Global Health Institute, Harding Distinguished Postgraduate Scholars Program and European Research Council, with additional support from the NIHR Cambridge Biomedical Research Centre.
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