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Preparation and Gene Modification of Nonhuman Primate Hematopoietic Stem and Progenitor Cells
Published on: February 15, 2019
Experience with synthetic vaccines for cancer and persistent virus infections in nonhuman primates and patients
Esther D Quakkelaar1, Cornelis J M Melief
1Department of Immunohematology, Leiden University Medical Center, Leiden, The Netherlands.
Abstract:
Synthetic vaccines, in particular long synthetic peptides of approximately 25-50 amino acids in length, are attractive for HIV vaccine development and for induction of therapeutic immune responses in patients with (pre-)malignant disorders. In the case of preventive vaccine development against HIV, no major success has been achieved, but the possibilities are by no means exhausted. A long peptide vaccine consisting of 13 overlapping peptides, which together cover the entire length of the two oncogenic proteins E6 and E7 of high-risk human papilloma virus type 16 (HPV16), caused complete regression of all lesions and eradication of virus in 9 out of 20 women with high-grade vulvar intraepithelial neoplasia, a therapy-resistant preneoplastic disorder. The nature and strength of the vaccine-prompted T cell responses were significantly correlated with the clinical response. Synthetic peptide vaccines are attractive, because they allow rational improvement of vaccine design and detailed pharmacokinetic and pharmacodynamic studies not possible with conventional vaccines. Improvements are possible by addition or conjugation of adjuvants, notably TLR ligands, to the synthetic peptides.
Insights
Synthetic peptide vaccines show promise for treating pre-malignant disorders like HPV-related lesions. A long peptide vaccine targeting human papillomavirus (HPV) proteins demonstrated significant clinical responses and virus eradication.
Area of Science:
- Vaccinology
- Immunology
- Oncology
Background:
- Synthetic vaccines, particularly long synthetic peptides (25-50 amino acids), offer potential for HIV vaccine development and treating pre-malignant disorders.
- Despite limited success in preventive HIV vaccine development, synthetic peptide vaccines present viable avenues for therapeutic immune responses.
Purpose of the Study:
- To evaluate the efficacy of a long synthetic peptide vaccine in treating high-grade vulvar intraepithelial neoplasia caused by human papillomavirus type 16 (HPV16).
- To investigate the correlation between T cell responses and clinical outcomes in patients receiving the synthetic peptide vaccine.
Main Methods:
- A synthetic peptide vaccine composed of 13 overlapping peptides targeting HPV16 E6 and E7 oncogenic proteins was administered.
- Immune responses, specifically T cell responses, were analyzed in relation to clinical efficacy.
Main Results:
- The long peptide vaccine led to complete regression of lesions and viral eradication in 9 out of 20 women with high-grade vulvar intraepithelial neoplasia.
- A significant correlation was observed between the nature and strength of vaccine-induced T cell responses and the clinical response.
Conclusions:
- Synthetic peptide vaccines, like the one targeting HPV16, are effective in treating therapy-resistant preneoplastic disorders.
- Rational design and adjuvant addition (e.g., TLR ligands) can further enhance the development and efficacy of synthetic peptide vaccines.
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