Table 2.
Lactic acid bacteria (LAB)-based vaccine studies.
Vaccines | ||||
---|---|---|---|---|
Animal Studies | ||||
Studied Agent | Route of Administration | Type of Study | Observed Effects | Ref |
Recombinant Lactobacillus casei expressing HPV16 E7 (LacE7) | Mucosal (oral) | Animal study | - Elicit E7-specific IFN gamma-producing cells (T cells with E7-type 1 immune responses) - Greater induction of T cells compared to subcutaneous or intramuscular antigen delivery. - Trigger mucosal cytotoxic cellular immune responses |
[185] |
L. lactis MG1363 was transformed with two types of HPV16 L1-encoding plasmids for intracellular expression or secretion. | Oral | Animal study | - Serum IgG responses after immunizations with L. lactis secreting HPV16 L1. - Vaginal IgA immune responses after oral immunization with L. lactis expressing HPV16 L1, but secreting HPV - HPV16 L1-specific mucosal immune responses affected by immunization frequency. |
[197] |
N-terminal L2 polypeptides comprising residues 11 to 200 derived from HPV16 produced in bacteria (HPV16 L2 11–200) | Vaccination | Animal study | - Effective protection of rabbits against cutaneous and mucosal challenge with CRPV and ROPV - Generation of broadly cross-neutralizing serum antibody - potential of L2 as a second-generation preventive HPV vaccine antigen. |
[200] |
A partial HPV-16 L2 protein (N-terminal 1–224 amino acid) on the surface of L. casei. | Mucosal (oral) | Animal study | - Production of L2-specific serum IgG and vaginal IgG and IgA in Balb/c mice - Trigger systemic and mucosal cross-neutralizing effects in mice |
[201] |
L. lactis NZ9000 expressing human papillomavirus type 16 E7 antigen | Mucosal (oral) | Animal study | - Elicit the highest levels of E7-specific antibody and numbers of E7-specific CD4+ T helper and CD8+ T cell precursors. - Potent protective effects against challenge with the E7-expressing tumour cell line (TC-1) - pNZ8123-HPV16-optiE7 containing L. lactis showed strong therapeutic antitumour effects against established tumours in vivo. - Trigger humoral and cellular immune responses in mice |
[202] |
Recombinant strains of L. lactis NZ9000 expressing native and codon-optimized E6 protein (fused to the SPusp45 secretion signal) | Mucosal (oral) | Animal study | - Improved inhibitory effect on tumour growth, improved treatment effects on progression of tumour size, and improved survival rates in comparison with L. lactis having native E6 oncogene - Induce humoral and cellular immunity |
[203] |
HPV16 E7 antigen expressed on the surface of L. casei | Mucosal (oral) vaccine | Animal study | - Enhanced E7-specific serum IgG and mucosal IgA production. - Reduced tumour size and increased survival rate in E7-based mouse tumour model compared to versus mice receiving control (L. casei-PgsA) immunization. |
[204] |
HPV16 E7-expressing L. casei (L. casei-E7) combined with γ-PGA secreted by Bacillus subtilis | Mucosal (oral) vaccine | Animal study (TC-1 mouse model) | - Enhanced innate immune response including activation of dendritic cells - Significantly suppressed growth of TC-1 tumour cells and an increased survival rate compared to mice vaccinated with L. casei-E7 alone. - Markedly enhanced activation of natural killer (NK) cells, no impact on E7-specific cytolytic activity of CD8+ T lymphocytes. |
[211] |
Combination of adenovirus expressing calreticulin-E7 (Ad-CRT-E7) and L. lactis encoding HPV-16 E7 (Ll-E7) anchored to its surface | Intranasal preimmunization of Ll-E7, followed by a single Ad-CRT/E7 application | Animal study (mouse model) | - ∼80% of tumour suppression compared to controls. - 70% survival rate 300 days post-treatment (100% of controls died by 50 days). - Significant CD8+ cytotoxic T-lymphocytes infiltration in tumours of mice treated with Ll-E7+Ad-CRT/E7. |
[212] |
Clinical Studies and Trials | ||||
Attenuated L. casei expressing modified full-length HPV16 E7 protein | Oral (during dose optimization studies (1, 2, 4, or 6 capsules/day) at weeks 1, 2, 4, and 8 (n = 10) or optimized vaccine formulation (n = 7) | Patients with HPV16-associated CIN3 | - Most patients (70%) receiving the optimized dose experienced a pathological down-grade to CIN2 at week 9 of treatment - E7-specific mucosal immunity was elicited in the uterine cervical lesions. |
[192] |
NZ8123-HPV16-optiE7 vaccine involving recombinant L. lactis expressing the codon-optimized human papillomavirus (HPV)-16 E7 oncogene | Oral vaccine or placebo | A dose-escalation, randomized, double-blind, placebo-controlled phase I clinical trial was performed in healthy Iranian volunteer women | - Vaccination was well tolerated, and no serious adverse effects were reported - Dose-dependent response to NZ8123-HPV16-optiE7 vaccine following oral administration - Safety and immunogenicity profile achieved in this study encourages further phase II trials with the 5 × 109 CFU/mL dose vaccine |
[205]. |
BLS-M07 (HPV 16 E7 antigen expressed on the surface of L. casei) | Oral administration Phase 1: 5 times a week, on weeks 1, 2, 4, and 8 with dosages of 500 mg, 1000 mg, and 1500 mg Phase 2a: 1000 mg dose. |
A phase 1/2a, dose-escalation, safety, and preliminary efficacy study performed in patients with CIN 3 | - No dose limiting toxicity. - No grade 3 or 4 treatment-related adverse events or deaths - Improved RCI grading (16 weeks after treatment) - Increased serum HPV16 E7 specific antibody production. |
[206] |