A recent study published in Communications Biology examined whether immunity developed from COVID-19 infection or vaccination offers protection against common cold coronaviruses. The research, based on data from the VIVALDI study involving 369 participants in long-term care facilities in England, focused on antibody and cellular responses to both SARS-CoV-2 and four endemic seasonal coronaviruses: OC43, HKU1, NL63, and 229E.
The study found that both infection with SARS-CoV-2 and vaccination produced strong antibody responses specific to the virus. However, these immune responses showed only limited cross-reactivity with the seasonal coronaviruses responsible for common colds. According to the researchers, "SARS-CoV-2 has established its own ecological niche without significantly disrupting established immunity patterns against other coronaviruses."
Before the emergence of COVID-19 in 2019, the four mentioned seasonal coronaviruses were already circulating globally and causing mild respiratory illnesses. The similarities between SARS-CoV-2 and these viruses led scientists to consider whether immunity to one could affect immunity to others.
Spike proteins on coronavirus surfaces are made up of two main regions: S1, which is highly variable and unique to each virus, and S2, which is more conserved across different coronaviruses. The study sought to determine if immune responses would target either region more strongly.
Participants were grouped by their history of infection and vaccination: uninfected/unvaccinated; infected/unvaccinated; uninfected/vaccinated; or those with hybrid immunity (both infected and vaccinated). Blood samples were analyzed for IgG antibodies targeting spike proteins from both SARS-CoV-2 and the endemic viruses. Cellular immune responses were also measured.
The results showed widespread pre-existing immunity to seasonal coronaviruses among participants. Exposure to SARS-CoV-2 did not change these baseline patterns. Infection increased virus-specific antibodies but had little effect on antibodies against related betacoronaviruses. Vaccination resulted in a stronger antibody response specific for SARS-CoV-2 than natural infection alone; hybrid immunity generated the highest levels overall. Antibody increases against endemic coronaviruses after vaccination or hybrid exposure remained modest.
Further analysis indicated that vaccine-induced antibodies mainly targeted the S1 domain of SARS-CoV-2’s spike protein. When S1-binding antibodies were removed from samples, most spike-binding IgG disappeared—demonstrating limited overlap with conserved regions shared by other human coronaviruses.
T cell analyses revealed that while responses targeted both S1 and S2 domains of SARS-CoV-2’s spike protein, they were much stronger than T cell responses observed for endemic viruses. For common cold viruses specifically, T cell activity was focused on the conserved S2 domain.
Researchers concluded that “COVID-19 vaccines induce exceptionally strong and specific antibody responses,” but do not provide broad or lasting protection against other human coronaviruses commonly associated with colds. They noted a key distinction between vaccine-induced immunity—which focuses narrowly on variable viral regions—and natural lifetime-acquired immunity that may recognize more conserved parts of viral proteins.
The findings suggest current COVID-19 vaccines remain effective at protecting against SARS-CoV-2 itself but should not be expected to offer broad coronavirus protection beyond this scope.
