Whey Proteins and Immunity: Mechanisms Underlying Immune System Reinforcement and Protection Against Viral and Bacterial Infections

This review aims to examine the immunological, anti-inflammatory, antiviral, and antibacterial activities of key whey and milk proteins, specifically lactoferrin, glycomacropeptide, β-lactoglobulin, α-lactalbumin and their derived peptides, particularly lactoferricin and lactoferrampin, highlighting their potential as preventive or therapeutic agents. Whey and dairy products represent complex biological matrices that, beyond their high nutritional value, serve as reservoirs of bioactive proteins and peptides with documented health-promoting properties. It has been reported that certain whey proteins (WPs) and whey-derived peptides may contribute to improvements in both innate and adaptive immunity, exert direct antiviral and antibacterial effects while also modulating host defenses through immunoregulatory, antioxidant, and anti-inflammatory activities. These mechanisms contribute not only to enhanced resistance against viral pathogens but also to maintaining intestinal homeostasis and microbiota balance, both of which are critical during infection. In recent years, particularly in the context of the COVID-19 pandemic, natural bioactive compounds derived from whey, and, more broadly, milk, have attracted increasing attention as potential adjuncts or alternatives to conventional antivirals, with reported activity not only against SARS-CoV-2, influenza but also other viral and microbial infections. Despite encouraging in vitro and in vivo evidence, clinical validation remains limited, and the antiviral and immunomodulatory effects of WPs still require deeper mechanistic clarification. Future research should focus on identifying molecular targets, as well as characterizing the pharmacokinetics and safety profiles of WPs and WP peptides across diverse clinical settings. At the same time, attention should be given to optimizing their application as nutraceuticals or functional dairy ingredients.