Table 1 HPV infection vaccines pre-clinical and clinical trials using L. lactis or L. casei
From: The potential use of bacteria and bacterial derivatives as drug delivery systems for viral infection
Vaccine | Bacteria | Vector | Study type | Administration route and dose | Type of immune response | Refs. |
|---|---|---|---|---|---|---|
NZ8123-HPV16-optiE7 vaccine | L. lactis | HPV-16 E7 oncogene | Phase I clinical trial with 55 individuals, IRCT20190504043464N1 | Oral, 20 dose, 1 × 109, 5 × 109, and 1 × 1010 CFU/mL | Antibody levels dropped till day 240, according to the 6 months follow-up, although long-lasting E7-specific IFN-γ-secreting CD8 + CTL responses were seen | [99] |
pNZ8123-HPV16-optiE7 vaccine | L. lactis NZ9000 | pNZ8123 | In vitro and in vivo, C57BL/6 mice | Oral, 1 × 108, 109, and 1010 CFU | The administration of recombinant L. lactis NZ9000 expressing the HPV type 16 E7 antigen via oral route in mice has been shown to elicit significant humoral and cellular immune responses | [100] |
BLS-M07 | Lactobacillus casei | HPV-16 E7 oncogene | A phase 1/2a Clinical Trial with 90 individuals, NCT02195089 | Oral, 5 times a week, on weeks 1, 2, 4, and 8, with dosages of 500Â mg, 1000Â mg, and 1500Â mg | The administration of BLS-M07 through oral means results in an elevation of serum HPV16 E7 specific Abs, stimulating the development of humoral immunity that protects against the virus | [101] |
HPV16 E7-expressing L. casei (GLBL101c) | Lactobacillus casei | pIGM2 | In vitro and in vivo, C57BL/6 mice | Oral, E7-doses but saturated beyond 0.3 μg/108 cells | The administration of IGMKK16E7 resulted in a four-fold increase in the stimulation of E7-specific mucosal IFNγ-producing cells in comparison to the previous method of immunization | [102] |
HPV-16/E6 | L. lactis NZ9000 | pNZ8123 | In vitro and in vivo, Female mice of strain C57BL/6 | Oral, 1 × 109 CFU | The study involved the oral immunization of female C57BL/6 mice using recombinant lactococci expressing inducible E6 oncoprotein. The resulting immune response was evaluated regarding antigen-specific antibody production, including IgA and IgG, as well as humoral, cell-mediated, and mucosal immune responses | [103] |
HPV-16/E7 (L. casei-E7) | Lactobacillus casei | HPV-16 E7 oncogen | In vivo, female C57BL/6 mice, experiments were performed according to the approved guidelines (KRIBB-AEC-16154, KRIBB-AEC-17036) | The administration of 800 μg of γ-PGA (2000 kDa) or PBS via the intragastric route was conducted orally five times per week during weeks 0, 3, 5, 6, and 7. The mice were orally administered with L. casei (5 × 109 cells/mouse) or L. casei-E7 (5 × 109 cells/mouse) five times per week during weeks 1, 2, 4, and 8 | According to the findings, the oral delivery of γ-PGA with L. casei-E7 elicits a cooperative antineoplastic outcome, along with humoral, cellular, and mucosal immune reactions | [104] |
HPV16 E7-expressing Lactobacillus (IGMKK16E7) | Lactobacillus casei | HPV-16 E7 oncogene | The present study is a phase I/II randomized trial that is placebo-controlled and double-blind, conducted across multiple centers. Its objective is to evaluate the safety and efficacy of IGMKK16E7 in individuals with HPV16-positive HSIL. The trial involves 41 participants and is registered under the UMIN000034253 and jRCT2031190034 | Oral administration, 0.5, 1, and 1.5Â g/day | The administration of IGMKK16E7 through the oral route is expected to induce a TH1 mucosal immune response specific to E7 | [105] |
HPV-16/E7 | L. lactis | pNZ8123 | In vitro and in vivo, C57BL/6 mice | Oral administration, 1 × 109 CFU/ml | The administration of recombinant L. lactis via oral immunization elicited notable humoral and cell-mediated immune responses in C57BL/6 mice. Specifically, significant increases in specific IgG and IgA Abs were observed in the serum and vaginal fluids, respectively, indicating a robust mucosal immune response | [106] |
NZ8123-HPV16-optiE6 vaccine | L. lactis | HPV-16 E6 oncogene | Phase I clinical trial with 46 individuals, 20190504043464N1 | Oral administration, 1 × 109, 5 × 109, and 1 × 1010 CFU/mL | The study observed that the maximum activation of E6-specific IFN-γ-secreting CD8 + CTL responses following oral immunization occurred one month after the final vaccination. The humoral, cellular, and mucosal immune responses are critical components of the immune system | [107] |