Probing changes to local and systemic immunity following intranodal injection

Abstract

Polymeric vaccine carriers protect and control delivery of encapsulated immune cues to target organs such as lymph nodes (LNs), tissues that coordinate adaptive immunity. Our lab recently established a non-surgical intranodal injection (i.LN.) technique allowing for control of the dose and combination of signals that reach inguinal LNs of mice. We discovered that after treating both inguinal LNs with a model antigen (Ovalbumin) and polymeric particles encapsulating a TLR3 agonist PolyIC (PolyIC MP), strikingly large increases to the percentage and number of activated dendritic cells and macrophages led to increases in B and T cells after 7 days. This treatment generated antigen-specific CD8⁺ T cells within the treated LNs (~3%) and blood (~13%) leading to memory phenotypes 28 days after vaccination. We used this system as a tool to study how local vaccine exposure and persistence impact systemic immunity by priming of one or more immune sites. Matching vaccine doses were deposited via i.LN. injection into one LN, two LNs, or with the antigen and adjuvant split into separate LNs. LNs receiving PolyIC MPs increased dendritic cell activation. Within the treated LNs, the highest percentage of antigen-specific CD8⁺ T cells occurred after treating one LN while treating two LNs resulted in half as many antigen-specific cells per LN. Interesting, while all treatments increased blood antigen-specific responses, the response to treating two LNs was double that of one LN treatment and six-fold higher than splitting the signals. These results indicate that the localization and kinetics of immune signals influences the magnitude of systemic immunity and could inform the design of future vaccine strategies to mount robust, antigen-specific responses.