Role of the Virome in Vaccine-Induced Immunization

The human virome—comprising viruses that can persist in a host, those that benefit the\r\nhost, and those that remain latent—has gained increasing acceptance as a modulator of\r\nimmune response toward vaccination. The factors known to influence vaccine efficacy\r\ninclude host genetics, age, and bacterial microbiota, while the virome is a much less\r\nconsidered fourth dimension. This article reviews how components of the virome such as\r\nTorque Teno Virus (TTV), cytomegalovirus (CMV), Epstein-–Barr virus\r\n(EBV), and bacteriophages impact both innate and adaptive immune responses,\r\nincluding mechanisms of immune pre-activation, trained immunity, and molecular\r\nmimicry from both beneficial and detrimental perspectives for vaccine-induced\r\nimmunization. Emphasis is given to immunocompromised populations such as transplant\r\nrecipients and those with HIV, where virome composition has been shown to correlate\r\nwith vaccine responsiveness. Experimental models support clinical observations on how\r\nchronic viral exposures can either enhance or inhibit vaccine efficacy. Finally, we\r\ndiscuss virome-aware precision vaccinology and call for the integration of the virome in\r\nthe development of immunization strategies, thus improving outcomes through\r\ncustomization.