Members of the TNF superfamily (TNFSF) of ligands and their receptors have emerged as promising targets in the treatment of autoimmune diseases and cancer, with several biologics gaining FDA approval. However, there are still many hurdles to realizing the true potential of targeting these superfamilies. This Review assesses past and ongoing clinical trials of agents modulating TNFSF ligands or receptors, highlighting ongoing challenges and future opportunities.

Vaccines play a critical role in combating infectious diseases, but their development faces challenges related to suboptimal efficacy, reactogenicity, slow development and high cost. This Review assesses emerging vaccine technologies aiming to address these limitations, focusing on advances in antigen and adjuvant selection and design, and next-generation delivery systems.

Engineered protein therapeutics, including antibodies, are valuable drugs offering major health benefits, but they can elicit unwanted immune responses. This Review identifies key challenges in assessing and mitigating the risk of immunogenicity, particularly the generation of anti-drug antibodies, and suggests pragmatic steps to address them.

Following the success of the COVID-19 vaccines, mRNA vaccines have now entered development for a wide range of infectious diseases. This Review discusses mRNA vaccine design considerations, delivery strategies and mechanisms of action, assessing mRNA vaccines currently in development for various viruses, bacteria and parasites. The challenges, limitations and opportunities facing next-generation mRNA vaccines are considered.