Nasal and Ocular Immunization with Bacteriophage Virus-like Particle Vaccines Elicits Distinct Systemic and Mucosal Antibody Profiles

<b>Background/Objectives</b>: Intramuscular immunization elicits systemic IgG and is the primary route of vaccine administration in humans. However, there is growing interest in utilizing other routes of administration to tailor antibody profiles, increase immunity at primary sites of infection, simplify administration, and eliminate needle waste. Here, we investigated the antibody profiles elicited by immunization with bacteriophage virus-like particle vaccine platforms at various routes of administration. <b>Methods</b>: We chose two model bacteriophage vaccines for investigation: bacteriophage MS2 virus-like particles (VLPs) recombinantly displaying a short, conserved peptide from <i>Chlamydia trachomatis</i> major outer membrane protein (MS2) and bacteriophage Qβ VLPs displaying oxycodone through chemical conjugation (Qβ). We comprehensively characterized the antibodies elicited systemically and at various mucosal sites when the vaccines were administered intramuscularly, intranasally or periocularly with or without an intramuscular prime using various prime/boost schemes. <b>Results</b>: Intranasal and periocular immunization elicited robust mucosal and systemic IgA responses for both MS2 and Qβ. The intramuscular prime followed by intranasal or periocular boosts elicited broad antibody responses, and increased antibodies titers at certain anatomical sites. <b>Conclusions</b>: These findings demonstrate the tractability of bacteriophage VLP-based vaccines in generating specific antibody profiles based on the prime-boost regimen and route of administration.