Cell-Cultured Influenza Vaccine Enhances IFN-γ+ T Cell and Memory T Cell Responses Following A/Victoria/2570/2019 IVR-215 (A/H1N1) Infection

Background: Influenza remains a significant public health challenge, with vaccination being a substantial way to prevent it. Cell-cultured influenza vaccines have emerged to improve on the drawbacks of egg-based vaccines, but there are few studies focusing on T cell immunity with both types of vaccines. Therefore, we studied the following 2022–2023 seasonal influenza vaccines with a standard dose and high dose: cell-based (C_sd and C_hd) and egg-based (E_sd and E_hd) vaccines. Methods: Along with a saline control group, C_sd, C_hd, E_sd, and E_hd vaccines were administered to BALB/c mice, followed by a challenge with the A/Victoria/2570/2019 (H1N1) strain. Results: After the challenge, four out of five mice in the saline group died by day 7 post-infection (P.I.). None of the vaccinated groups experienced over 20% weight loss or any deaths. On day 7 P.I., the lung viral load in the saline group (mean log value of 4.17) was higher than that in the vaccinated groups, with the C_sd group showing the lowest viral load (mean log value of 3.47). The C_sd group showed a significantly high response in macrophage 1 (M1), IFN-γ+ T cells, and tissue-resident memory (T_RM) T cells compared with the E_sd group on day 2 P.I. These M1, IFN-γ+ T cells, and T_RM cells showed similar trends (p < 0.01). In terms of humoral immunity, only the E_hd group showed HAI titers above 40 for all four strains before and after the challenge. Conclusions: The high levels of T cells in the cell-cultured vaccines suggest, pending further real-world research, that these vaccines may offer advantages.