Could Covid Boosters protect against emerging Covid strains

COVID-19 boosters may confer cross-protection against animal coronaviruses with pandemic potential Antibodies generated by current COVID-19 vaccines neutralise several bat and pangolin coronaviruses that have never infected humans but are considered potential future spillover threats, according to research led by scientists at the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), University of Cambridge. A companion study by the same group further demonstrated that a person's first exposure to severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) leaves a lasting immune "fingerprint" that constrains responses to later variants. The findings, published in npj Vaccines and iScience, suggest that repeated boosting could offer a degree of pre-emptive protection against related sarbecoviruses, while also underscoring the need for next-generation vaccines that can overcome immune imprinting to protect diverse populations. The researchers analysed blood samples from older UK adults (average age around 69) enrolled through the National Institute for Health and Care Research (NIHR) BioResource, all of whom had received 4 COVID-19 vaccine doses, including a recent bivalent booster containing both the original Wuhan strain and the Omicron variant. Antibody neutralisation was assessed against a panel of Omicron subvariants, SARS-CoV-1 (the virus responsible for the 2003 outbreak), and a range of sarbecoviruses circulating in bats and pangolins. As anticipated, neutralising activity waned against more recent Omicron variants and was poor against the genetically more distant SARS-CoV-1. Unexpectedly, however, antibodies neutralised 2 sarbecoviruses -- one of bat origin and one from pangolins -- more effectively than they did the original Wuhan strain, despite these viruses having no history of human infection. Several of the animal viruses tested were shown to be capable of entering human cells. "We'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," said joint first author Grace West of CITIID. Joint first author Rebecca Morse, also of CITIID, added: "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." In the companion iScience study, the Cambridge team, working with Nigerian collaborators, examined blood samples collected in early 2023 from unvaccinated adults in Nigeria, most of whom had already been exposed to SARS-CoV-2, often multiple times, despite never having been formally diagnosed. Two independent cohorts sampled while Omicron was circulating provided a rare opportunity to characterise immunity established through infection rather than vaccination. Despite subsequent Omicron infection, antibody responses remained dominated by earlier strains -- a phenomenon known as immune imprinting. When antibodies targeting earlier strains were experimentally removed, the samples lost most of their capacity to neutralise both earlier variants and Omicron, indicating that responses to newer variants were built largely on pre-existing immune memory. Vaccination amplified this imprinted response rather than generating strong new responses to Omicron. "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," said first author Adam Abdullahi, PhD, of CITIID and the Institute of Human Virology in Abuja, Nigeria. "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." Ravindra Gupta, MD, PhD, The Hong Kong Jockey Club Professor of Global Health at CITIID, 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." Professor Gupta added that "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." Joint lead author Alash'le Abimiku, PhD, of the Institute of Human Virology, Nigeria, added: "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 account for the cross-protective effect observed in the npj Vaccines study: because the spike proteins of certain bat and pangolin viruses more closely resemble the Wuhan strain than those of Omicron, imprinted antibody responses may cross-react more effectively with these animal viruses than with newer human variants. The authors suggested that vaccines targeting conserved regions of the spike protein shared across sarbecoviruses could broaden protection. Source: University of Cambridge