Use of anti-CTLA4 as a molecular adjuvant to support dose sparing of adenoviral vectored vaccines 2800

Description Background Viral vectored vaccines are vital for combating infectious diseases, but supply can be limited in pandemic settings. Studies suggest co-administering anti-CTLA4 can enhance immune responses, offering a potential dose-sparing strategy. Aim: To evaluate whether adenoviral vector-encoded anti-CTLA4 (Ad6-9D9) can support dose sparing of a SARS-CoV-2 adenoviral vector vaccine (Ad26-Spike). Methods Six-week-old C57BL/6 mice were immunised intramuscularly with Ad26-Spike (2e07 or 1e08 vp/mouse) with or without Ad6-9D9 (1e08 vp/mouse). Blood and splenocytes were collected on days 14, 21, 28 and 42 post-vaccination to analyse Spike-specific IgG (ELISA) and CD8+ tetramer responses (FACS). Results Co-administration of Ad6-9D9 increased Spike-specific IgG responses at days 14, 21, and 28, with statistical significance observed at day 14 and 28 for the 2e07 vp/mouse group (1:625 vs 1:12.5, p = 0.01). Enhanced CD8+ tetramer responses were observed at earlier timepoints in both dose groups with Ad6-9D9. 2e07vp Ad-Spike elicited significantly weaker humoral and cellular responses compared to 1e08vp. However, addition of Ad6-9D9 made the responses comparable, showing that Ad6-9D9 can be used for 1/5 dose sparing. Ad6-9D9 also increased the frequency of vaccine responders in the 2e07vp group (p = 0.0021). Conclusions Ad6-9D9 co-administration boosts early humoral and cellular immunity without compromising long term responses, supporting its potential for dose sparing in pandemics.