New Perspectives in Therapeutic Vaccines for HPV: A Critical Review
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
4.1. HPV Vaccines Based on L2 Protein: Rationale
4.2. HPV Immunological Response and L2 Therapeutic Vaccines
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study Author and Years | Composition | Main Advantages Reported | Develop Phase |
---|---|---|---|
De Jong et al., 2002 [27] | TA-CIN vaccine (recombinant HPV-16 L2 E6 E7) | Immunological profile: revealed a significant anti HPV-16 E6 and E7 T cell response in 8/11 patients treated with TA-CIN vaccine. Immunological response with IgG production was reported. No reported serious or severe adverse events. | Phase I |
Davidson et al., 2003 [15] | Therapeutic vaccine based on modified HPV-16 and 18 E6–E7 proteins | Evaluation of vaccines in vulvar intraepithelial neoplasia. Ten patients demonstrated an increase in HPV-16 specific T-CELL response. In one patient, there was a complete regression of vulvar lesions and viral clearance by PCR evaluation. In eight patients, a reduction in vulvar lesions of at least 50% of diameter was reported, and in 6 of these women, a reduction in viral load. Four patients showed a decrease in symptoms. All patients reported an increase in both serological and cell-mediated immunity. | Phase II |
Smith et al., 2004 [28] | TA-CIN vaccine (recombinant HPV-16 L2E6E7) | Evaluation of vaccine application in high-grade ano-genital intraepithelial neoplasm. Regarding the proliferative responses against the oncoproteins E6 and E7, there was only a significant increase in the response for E6. HPV-16 E6-specific T cell responses in 9 patients, induced by vaccination. In two women, HPV-16 E7-specific T cells were enhanced after all vaccinations. Three patients reported enhanced HPV-18 E6-specific T-cell activity after vaccination. No significant changes were reported in serological responses to HPV-18 E6 or E7 after vaccination. Among 19 patients with stable disease, 8 reported an immunogenic response, and in the 4 patients with disease progression, two did not show a T-cell response and two revealed an absence of both a T-cell and a humoral response | Phase II |
Davidson et al., 2004 [29] | TA-CIN vaccine (recombinant HPV-16 L2 E6 E7) and TA-HPV (vaccine based on virus encoding HPV16/18 and E7) | Ten women affected by HPV-16 related VIN were enrolled. Three patients reported a clinical response, while 6 patients maintained stable disease. Two patients reported a partial or complete clinical response, which was confirmed by the reduction in lesion diameter of ≥50%. Six patients maintained stable disease, one patient reported significant symptomatic relief following vaccination, while one patient reported disease progression (increase in lesion diameter of ≥25% post-vaccination). IgG levels did not demonstrate a significant change. Regarding HPV-specific proliferative responses, all patients demonstrated a proliferative response. | Phase II |
Fainder et al., 2006 [30] | TA-CIN vaccine (recombinant HPV-16 L2 E6 E7) and TA-HPV (vaccine based on virus encoding HPV16/18 and E7) | Patients with ano-genital intraepithelial neoplasia were vaccinated with 3 doses of TA-CIN followed by one dose of a recombinant vaccine with virus encoding HPV-16 and 18 E6/E7 (TA-HPV). Two with VAIN 3, 27 with VIN3 and 2 patients with VIN3 also had anal intraepithelial neoplasia. A complete response was seen in 1 patient, partial response in 5, stable disease in 18, and progression in 5 of them. None of the patients developed invasive lesions. | Phase II |
Dayana et al. 2010 [31] | TA-CIN vaccine (recombinant HPV-16 L2 E6 E7) and Imiquimod | Women with VIN2 and VIN3 were enrolled. A complete regression of VIN in 12/19 at week 52 of treatment (63%). In responder patients, there was a significant increase in a CD4+ and a CD8+ response. The authors concluded that the modulation of local and systemic immune response plays a role in the therapeutic vaccine effect. | Phase II |
Safety and Feasibility of TA-CIN Vaccine in HPV16 Associated Cervical Cancer [31] | TA-CIN vaccine (recombinant HPV-16 L2 E6 E7) | (ongoing study) The first aim of this trial is to provide evidence for the safety and feasibility of the vaccine and the different immune responses when the dose is administered at different locations such as the thigh or the arm in order to determine the site that can elicit the most potent immunological effect. Secondary aims were the evaluation of the level of circulating antibodies to HPV-16 E6, E7, and L2, the level of circulating T-Cells and the mononucleocyte response in the peripheral blood before and after vaccination | Phase I |
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Gardella, B.; Gritti, A.; Soleymaninejadian, E.; Pasquali, M.F.; Riemma, G.; La Verde, M.; Schettino, M.T.; Fortunato, N.; Torella, M.; Dominoni, M. New Perspectives in Therapeutic Vaccines for HPV: A Critical Review. Medicina 2022, 58, 860. https://doi.org/10.3390/medicina58070860
Gardella B, Gritti A, Soleymaninejadian E, Pasquali MF, Riemma G, La Verde M, Schettino MT, Fortunato N, Torella M, Dominoni M. New Perspectives in Therapeutic Vaccines for HPV: A Critical Review. Medicina. 2022; 58(7):860. https://doi.org/10.3390/medicina58070860
Chicago/Turabian StyleGardella, Barbara, Andrea Gritti, Ehsan Soleymaninejadian, Marianna Francesca Pasquali, Gaetano Riemma, Marco La Verde, Maria Teresa Schettino, Nicola Fortunato, Marco Torella, and Mattia Dominoni. 2022. "New Perspectives in Therapeutic Vaccines for HPV: A Critical Review" Medicina 58, no. 7: 860. https://doi.org/10.3390/medicina58070860