COVID-19 Boosters May Offer Head Start Against Future Animal Coronaviruses, But Immune "Imprinting" Complicates the Picture

Two new Cambridge studies add nuance to the ongoing conversation surrounding long-term COVID-19 immunity. The first suggests current COVID-19 boosters may offer partial protection against some animal coronaviruses with pandemic potential, whereas the second helps explain why that protection does not always extend smoothly to newer variants.¹

Boosters and Cross-Protection Against Zoonotic Coronaviruses

Investigators at the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID) tested blood samples from older UK adults, with a mean age of about 69 years, who had received 4 COVID-19 vaccine doses, including a bivalent booster containing components from both the ancestral Wuhan strain and an Omicron lineage. Neutralizing activity declined against newer Omicron sublineages compared with the original strain, consistent with the virus's ongoing immune escape. Antibodies were also weak against SARS-CoV-1, the more genetically distant virus responsible for the 2003 SARS outbreak.^1,2

However, those same antibodies neutralized 2 sarbecoviruses—one isolated from bats, one from pangolins—more effectively than they neutralized the original Wuhan strain, despite neither virus ever having infected a human. Several of the animal coronaviruses tested can already bind the human ACE2 receptor, a key requirement for zoonotic spillover.^1,2

When asked what this means for booster recommendations in older or immunocompromised patients, senior study author Ravindra Gupta, MBBS, PhD, professor of global health at CITIID, University of Cambridge, was direct. "The phenomenon of cross protection against certain animal coronaviruses does not change the recommendations," he told Pharmacy Times.

Nonetheless, the researchers suggested the findings support development of next-generation vaccines targeting conserved regions of the spike protein shared across multiple coronaviruses, rather than only the regions most prone to mutation.¹

Why "First Impressions" Still Matter

A related study, published in iScience, helps explain the variant-specific decline. Analyzing blood from unvaccinated adults in Nigeria, the team found that most participants had already been infected with SARS-CoV-2—often more than once—well before any formal diagnosis. Despite later Omicron exposure, antibody responses remained dominated by earlier viral strains, a phenomenon known as immune imprinting.³

When researchers experimentally removed antibodies targeting the earliest strains, neutralizing capacity against both older and newer variants dropped sharply, confirming that later responses were largely built on initial immune memory rather than generated anew. Vaccination amplified that existing memory more than it generated fresh responses to Omicron-era variants.³

For pharmacists wondering whether patients infected before ever being vaccinated need different counseling, Gupta noted the immune system doesn't draw a sharp line between the 2 routes of exposure: "Infection and vaccines have similar effects on the immune system in terms of 'locking in,' and so we don't have to treat those with prior infection differently.”

Clinical Implications for Pharmacy Practice

Together, the studies suggest a patient's first viral encounter—whether through infection or vaccination—continues to shape, and in some ways constrain, future immune responses. For pharmacists, this carries 2 practical takeaways.

First, continuing to recommend boosters for older and immunocompromised patients remains worthwhile, because cross-reactive immunity could blunt the severity of a future spillover event even before a matched vaccine exists. For patients skeptical about getting yet another booster, Gupta explained, “[They] are a way of helping direct the immune system towards the rapidly changing virus.”¹

Second, variability in patients' "first exposure"—shaped by infection history, geography, and vaccination timing—may help explain inconsistent variant-specific protection observed in practice, independent of adherence to dosing schedules.³

Public health authorities continue to flag zoonotic coronaviruses among pathogens of pandemic concern, underscoring why pharmacist-led vaccine counseling remains central to preparedness strategy. Should next-generation, spike-conserved-region vaccines reach the market, they may eventually give pharmacists a tool that sidesteps the imprinting problem altogether. ^1,3-5

When asked how imprinting should inform that next generation of vaccine design, Gupta acknowledged the question is far from settled. "…We do not know for sure what the answer is, but repeated vaccination with different variants eventually appears to redirect immunity to newer variants," he said. "The next generation of vaccines might enable broad targeting of all possible variants, though this is easier said than done."

REFERENCES

1. COVID-19 vaccine boosters may help protect against future animal coronaviruses. University of Cambridge. News release. EurekAlert! July 1, 2026. Accessed July 1, 2026. https://www.eurekalert.org/news-releases/1133578

2. Morse RB, Sievers BL, Rihn SJ, Gupta RK, et al. COVID-19 vaccination induces cross-neutralization of sarbecoviruses related to SARS-CoV-2. npj Vaccines (preprint: bioRxiv) doi:2025.04.04.647203.

3. Abdullahi A, Morse RB, Kin Cheng MT, et al. SARS-CoV-2 Omicron infection reveals imprinted antibody responses in the absence of vaccination. iScience. 2026;29(6):115910. doi:10.1016/j.isci.2026.115910

4. Six major health threats that could shape 2026: here's what experts are watching. Gavi, VaccinesWork. February 19, 2026. Accessed June 29, 2026. https://www.gavi.org/vaccineswork/six-major-health-threats-could-shape-2026-heres-what-experts-are-watching

5. Holmes I, Vora NM, Gurley ES, et al. Assessing evidence to guide primary prevention of pathogen X. Emerg Infect Dis. 2026;32(6):1-6. doi:10.3201/eid3206.260293