crossimmunity

Crossimmunity, also called heterologous immunity, is a form of immune protection wherein exposure to one pathogen provides partial protection against a related pathogen. This protection can reduce susceptibility to infection, lessen disease severity, or alter clinical outcomes, even without direct exposure to the second pathogen. Crossimmunity arises from immune memory or innate training that recognizes shared antigenic determinants across related organisms.

Crossimmunity can be humoral or cell-mediated. Humoral cross-immunity involves antibodies that bind to conserved epitopes common to related pathogens, potentially neutralizing the second pathogen. Cell-mediated cross-immunity involves memory T cells that recognize similar peptide fragments presented by MHC, enabling a faster and more robust response. Innate mechanisms, including trained immunity in which innate immune cells display enhanced responsiveness, can also contribute. The extent and duration of cross-immunity depend on the degree of antigenic similarity, timing of prior exposures, and host factors. Immune imprinting or original antigenic sin can shape subsequent responses, sometimes favoring responses to familiar epitopes at the expense of novel ones.

Classic examples include cross-protection conferred by vaccines from related pathogens, such as cowpox vaccination providing protection against smallpox. In natural infections, prior exposure to related viruses or bacterial strains can influence subsequent susceptibility or disease course, such as heterologous immunity between related influenza strains or coronaviruses. In populations, cross-immunity can affect transmission dynamics and the interpretation of serological surveys, and it influences considerations for vaccine design, which increasingly target conserved epitopes to maximize cross-protection while minimizing immune interference.