Research Topic

Heterologous Immunity: Implications and Applications in Vaccines and Immunotherapies

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Strict clonal specificity to antigenic epitopes is the hallmark of adaptive immune T and B cells. However, this dogma has been challenged by the continued demonstration of heterologous responses or cross-reactivity, whereby exposure or priming by one microbe/pathogen/antigen induces T and B cells capable of ...

Strict clonal specificity to antigenic epitopes is the hallmark of adaptive immune T and B cells. However, this dogma has been challenged by the continued demonstration of heterologous responses or cross-reactivity, whereby exposure or priming by one microbe/pathogen/antigen induces T and B cells capable of recognizing epitopes from totally unrelated antigens with little structural homology.

Two lines of experimental observations have proven the existence of heterologous immunity: i) T cells and antibodies from humans which have not been exposed to a specific pathogen often demonstrate immune responses against antigens from those pathogens; and ii) when mice are infected with a specific microbe (viruses, bacteria, parasites etc.) or immunized with their derived antigens, they demonstrate T and B cell responses against an unrelated pathogen/microbe/antigen. Heterologous immunity is not only recognized by empirical experimental observations, but it is also being supported mechanistically at the clonal level and by physicochemical, biochemical and molecular approaches. Theoretically, there is a vast imbalance in the available clonotypes vs. the pathogenic epitopes that one must respond to in a life-time, on the order of >106 fold, necessitating a broadly cross-reactive T cell and antibody repertoire for successful survival of humans among numerous invading pathogens.

Heterologous immunity could have both a harmful and a beneficial effect. Immunological exposure to one pathogen/antigen has the potential to modulate immunity against another pathogen in a detrimental manner by shifting the immune hierarchy of protective immune epitope specificities, thereby affecting pathogenesis and vaccine efficacy. Alternatively, vaccines developed against one pathogen have the potential to generate protective immunity against variants of that pathogen or a totally different pathogen. In addition, immune escape variants of pathogens have the potential to be recognized by cross-reactive cells. There are reports on the existence of cross-reactive immunity between evolutionarily unrelated viruses such as influenza A virus and hepatitis C virus (HCV), adenoviruses and HCV, lymphocytic choriomeningitis virus (LCMV) and dengue virus (DV) etc. There are also reports on cross-reactive immunity between evolutionary divergent pathogens such as viruses and bacteria (HIV and vaccinia virus with Mycobacterium) and fungi and bacteria (Candida with Staphylococcus and Acinetobacter). The heterologous immunity adds a whole new dimension to the investigation of vaccines as well as monoclonal antibody-based anti-microbial therapies.

This Research Topic will provide new insights into the concept and principles of heterologous (cross-reactive) T and B cell immunity and include experimental observations, mechanisms of heterologous immunity, and implications in disease progression and pathogenesis. We also look for submissions that report vaccine design based on the concept of heterologous immunity, broader antigen/pathogen reactivity, common protective epitope inclusion and non-protective epitope deletion. Finally, we will gather submissions reporting monoclonal antibody based-therapies targeting multiple pathogens that are designed based on common protective epitopes among these pathogens. We welcome manuscripts in the form of Original Research articles, Reviews, Mini-Reviews as well as Hypothesis and Theory articles.


Keywords: Heterologous, Cross-reactive, T cells, B cells, Antibodies, Vaccines, Immune modulation, Antigen-MHC complex, TCR-pMHC complex, Epitopes


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