Work

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

Year: 2025

Type: article

Abstract: 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. Funding Sources Supported by Wellcome grant (222426/Z/21/Z) Topic Categories Vaccines and Immunotherapy (VAC)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.681