Heterologous Immunity: Role in Natural and Vaccine-Induced Resistance to Infections

The central paradigm of vaccination is to generate resistance to infection by a specific pathogen when the vacinee is re-exposed to that pathogen. This paradigm is based on two fundamental characteristics of the adaptive immune system, specificity and memory. These characteristics come from the clonal specificity of T and B cells and the long-term survival of previously-encountered memory cells which can rapidly and specifically expand upon re-exposure to the same specific antigen. However, there is an increasing awareness of the concept, as well as experimental documentation of, heterologous immunity and cross-reactivity of adaptive immune lymphocytes in protection from infection. This awareness is supported by a number of human epidemiological studies in vaccine recipients and/or individuals naturally-resistant to certain infections, as well as studies in mouse models of infections, and indeed theoretical considerations regarding the disproportional repertoire of available T and B cell clonotypes compared to antigenic epitopes found on pathogens. Heterologous immunity can broaden the protective outcomes of vaccinations, and natural resistance to infections. Besides exogenous microbes/pathogens and/or vaccines, endogenous microbiota can also impact the outcomes of an infection and/or vaccination through heterologous immunity. Moreover, utilization of viral and/or bacterial vaccine vectors, capable of inducing heterologous immunity may also influence the natural course of many infections/diseases. This review article will briefly discuss these implications and redress the central dogma of specificity in the immune system.