The influenza virus is one of the major global health concerns, causing significant morbidity and mortality in both humans and animals, with substantial impacts on public health. Vaccination remains the primary strategy for managing influenza virus infections; however, the virus undergoes frequent genetic changes through antigenic drift and shift. These mutations lead to new seasonal strains that evade pre-existing immunity. These mutations can potentially result in virulent strains that could trigger future pandemics. Therefore, developing a vaccine capable of providing robust protection despite these genetic changes is essential. Vaccine adjuvants are essential for boosting and directing the immune system’s response, broadening the spectrum of protection, and reducing the amount of antigen required to achieve protection, which is particularly valuable in the face of rapidly evolving strains and during pandemics. Recent advances in adjuvant design and formulation strategies have demonstrated promising improvements in both the overall potency and durability of influenza vaccines, importantly, significant reductions in losses due to influenza infection. This review highlights the current status of different types of influenza virus vaccines, their benefits, and challenges. Further, the review focuses on the role of adjuvants, discussing their advantages, limitations, and methodological approaches, while also considering their potential contribution in developing a universal flu vaccine intended to provide extensive and lasting protection.

The innate immune system provides the first line of defense against invading pathogens and relies on tightly regulated mechanisms to initiate and resolve inflammatory responses. In addition to transcriptional control, post-transcriptional regulation of messenger RNA (mRNA) plays a critical role in determining the magnitude and duration of immune responses. Among those key regulators, the ZFP36 family of CCCH-type zinc-finger RNA-binding proteins, including ZFP36, ZFP36L1, and ZFP36L2, plays a central role in controlling the stability and translation of inflammatory, immune-related, and viral RNAs. This review focuses on the ZFP36 family of RNA-binding proteins and highlights their emerging roles in inflammation, immune cell development and differentiation, and antiviral immunity, with a particular focus on ZFP36L1 and ZFP36L2. Recent evidence has identified ZFP36L1 as a broad-spectrum antiviral factor that restricts multiple RNA viruses through distinct molecular mechanisms. A detailed understanding of the molecular mechanisms underlying ZFP36L1- and ZFP36L2-mediated antiviral activity and immune regulation will facilitate rational development of host-directed antiviral therapeutics and their strategic integration with vaccination strategies to limit viral replication, shedding, and transmission, thereby improving the control of emerging and re-emerging viral diseases.