Facile Conjugation Method of CpG‐ODN Adjuvant to Intact Virions for Vaccine Development

Vaccines are a pivotal achievement in public health, offering inexpensive, distributable, and highly effective protection against infectious diseases. Despite significant advancements in vaccine development, there are still many diseases for which vaccines are unavailable or offer limited protection. The global impact of the deficiency in vaccine‐induced immunity against these diseases is profound, leading to increased rates of illness, more frequent hospitalizations, and higher mortality rates. Recent studies have demonstrated conjugation mechanisms and delivery methods to copresent adjuvants and protein epitopes to antigen‐presenting cells, significantly enhancing adaptive immunity A novel approach is introduced to incorporate an adjuvant into the vaccine by covalently attaching it to whole enveloped virions. Using “clickable” azide‐enabled viral particles, generated through metabolic incorporation of N‐azidoacetyl glucosamine (GlcNAz), the virions with a cyclo‐octyne‐modified CpG‐ODN is conjugated. Conjugation yielded a potent adjuvant‐virus complex, eliciting higher TLR9‐mediated cell activation of cultured bone marrow‐derived macrophages relative to coadministered adjuvants and virions. Administration of covalent adjuvant‐virion conjugates increases immune cell stimulation and may provide a generalizable and effective strategy for eliciting a heightened immune response for vaccine development.