The First Clinical Use of a Recombinant Lactococcus lactis Expressing Human Papillomavirus Type 16 E7 Oncogene Oral Vaccine: A Phase I Safety and Immunogenicity Trial in Healthy Women Volunteers

HPV-16 E7-specific serum IgG antibody (1, top) and E7-specific vaginal IgA antibody (2, bottom) levels by placebo groups [cohorts 1 (A, left); 1 × 10⁹ CFU/mL dose, cohorts 2 (B, center); 5 × 10⁹ CFU/mL dose, and cohorts 3 (C, right); 1 × 10¹⁰ CFU/mL dose] and vaccine group [cohorts 4 (A, left); 1 × 10⁹ CFU/mL dose, cohorts 5 (B, center); 5 × 10⁹ CFU/mL dose, and cohorts 6 (C, right); 1 × 10¹⁰ CFU/mL dose] measured by ELISA at a serum dilution of 1:100 using goat anti-human IgG H&L (HRP) antibody and at a vaginal fluid dilution of 1:10 using goat anti-human IgA alpha chain (HRP) antibody, respectively. Results are expressed with 95% CIs for the following time points: prevaccination (day 0), days 30, 60, 90, and 240. The absorbance of each well was measured at 450 nm. Bars represent the mean ± standard error value of each group. Statistically significant differences are denoted by an asterisk between T60 and T30, T90, and T240 of vaccine groups (*, P ≤ 0.0001; **, P ≤ 0.001; ***, P ≤ 0.05; ****, P ≤ 0.1).

E7_11–20-specific IFNγ-secreting CD8⁺ CTL responses in cervical lymphocytes (1, top) and PBMCs (2, bottom) for samples from the same donor; placebo groups [cohorts 1 (A, left); 1 × 10⁹ CFU/mL dose, cohorts 2 (B, center); 5 × 10⁹ CFU/mL dose, and cohorts 3 (C, right); 1 × 10¹⁰ CFU/mL dose] and vaccine group [cohorts 4 (A, left); 1 × 10⁹ CFU/mL dose, cohorts 5 (B, center); 5 × 10⁹ CFU/mL dose, and cohorts 6 (C, right); 1 × 10¹⁰ CFU/mL dose] at different time points; before (day 0) and after immunizations (days 30, 60, 90, and 240). Each sign represents one woman. Data are reported as mean ± SD. Results are expressed as spot‐forming cells per number of cells with 95% CIs. Statistically significant differences are denoted by an asterisk between T90 and T30, T60, and T240 of vaccine groups (*, P ≤ 0.0001; **, P ≤ 0.001; ***, P ≤ 0.05; ****, P ≤ 0.1; *****, P ≤ 1).

E7_49–57-specific IFNγ-secreting CD8⁺ CTL responses in cervical lymphocytes (1, top) and PBMCs (2, bottom) for samples from the same donor; placebo groups [cohorts 1 (A, left); 1 × 10⁹ CFU/mL dose, cohorts 2 (B, center); 5 × 10⁹ CFU/mL dose, and cohorts 3 (C, right); 1 × 10¹⁰ CFU/mL dose] and vaccine group [cohorts 4 (A, left); 1 × 10⁹ CFU/mL dose, cohorts 5 (B, center); 5 × 10⁹ CFU/mL dose, and cohorts 6 (C, right); 1 × 10¹⁰ CFU/mL dose] at different time points; before (day 0) and after immunizations (days 30, 60, 90, and 240). Each sign represents one woman. Data are reported as mean ± SD. Results are expressed as spot‐forming cells per number of cells with 95% CIs. Statistically significant differences are denoted by an asterisk between T90 and T30, T60, and T240 of vaccine groups (*, P ≤ 0.0001; **, P ≤ 0.001; ***, P ≤ 0.05; ****, P ≤ 0.1; *****, P ≤ 1).

E7_86–93-specific IFNγ-secreting CD8⁺ CTL responses in cervical lymphocytes (1, top) and PBMCs (2, bottom) for samples from the same donor; placebo groups [cohorts 1 (A, left); 1 × 10⁹ CFU/mL dose, cohorts 2 (B, center); 5 × 10⁹ CFU/mL dose, and cohorts 3 (C, right); 1 × 10¹⁰ CFU/mL dose] and vaccine group [cohorts 4 (A, left); 1 × 10⁹ CFU/mL dose, cohorts 5 (B, center); 5 × 10⁹ CFU/mL dose, and cohorts 6 (C, right); 1 × 10¹⁰ CFU/mL dose] at different time points; before (day 0) and after immunizations (days 30, 60, 90, and 240). Each sign represents one woman. Data are reported as mean ± SD. Results are expressed as spot‐forming cells per number of cells with 95% CIs. Statistically significant differences are denoted by an asterisk between T90 and T30, T60, and T240 of vaccine groups (**, P ≤ 0.001; ***, P ≤ 0.05; ****, P ≤ 0.1; *****, P ≤ 1).