---
title: "HPV16 nanovaccine candidate: IL-15–E7 fusion protein in silk-fibroin nanoparticles"
id: "pubmed-42501767"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42501767"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42501767/"
doi: "10.1016/j.ijpharm.2026.127223"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# HPV16 nanovaccine candidate: IL-15–E7 fusion protein in silk-fibroin nanoparticles
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42501767
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42501767/)
- **DOI:** [10.1016/j.ijpharm.2026.127223](https://doi.org/10.1016%2Fj.ijpharm.2026.127223)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study developed a **nanovaccine** candidate targeting HPV16 by creating a recombinant fusion protein of **Interleukin-15 (IL-15)** linked to the HPV16 **E7 oncoprotein**, then encapsulating that fusion protein in **silk fibroin nanoparticles (SFNPs)**. - Nanoparticle characterization showed a nano-sized formulation measuring **77.402 ± 7.852 nm** with a net negative charge (zeta potential **-11.1 mV**). - In a mouse tumor challenge model, the IL-15–E7 SFNP formulation elicited stronger cellular immune markers than the unconjugated recombinant fusion protein, specifically higher **IFN-γ** and **Granzyme B** secretion. - Survival after tumor challenge was higher in mice immunized with the nanovaccine compared with recombinant IL-15–E7 alone (reported **75% vs 50%**). - Tumor growth inhibition favored the nanovaccine but was described as a non-significant substantial inhibition versus the recombinant protein. - Overall immunologic effects attributed to the IL-15–E7 SFNPs included induction of **Th1 immunity**, increased **cytotoxic T lymphocyte (CTL)** activity, and measurable **anti-tumor effects** in the preclinical model. - The report identifies the HPV16 **E7 oncoprotein** as a key therapeutic antigen for cervical cancer vaccine design and positions IL-15 as an immune-stimulatory adjuvant fused to antigen. - Specific experimental details such as immunization dose, schedule, number of animals per group, full statistical analyses, and safety/tolerability data were not reported in the PubMed abstract and thus are not available from this source.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jul 25. # Development of HPV nanovaccine candidate based on IL-15-E7 fusion protein encapsulated in silk-fibroin nanoparticles [Maryam Zeynali](https://pubmed.ncbi.nlm.nih.gov/?term=Zeynali+M&cauthor_id=42501767)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42501767/#full-view-affiliation-1 "Department of Biology, SR.C., Islamic Azad University, Tehran, Iran."), [Shiva Irani](https://pubmed.ncbi.nlm.nih.gov/?term=Irani+S&cauthor_id=42501767)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42501767/#full-view-affiliation-1 "Department of Biology, SR.C., Islamic Azad University, Tehran, Iran."), [Mehdi Farokhi](https://pubmed.ncbi.nlm.nih.gov/?term=Farokhi+M&cauthor_id=42501767)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42501767/#full-view-affiliation-2 "National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran. Electronic address: M_farokhi@pasteur.ac.ir."), [Azam Bolhassani](https://pubmed.ncbi.nlm.nih.gov/?term=Bolhassani+A&cauthor_id=42501767)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42501767/#full-view-affiliation-3 "Department of Hepatitis, AIDS and Blood-borne Diseases, Pasteur Institute of Iran, Tehran, Iran. Electronic address: A_bolhasani@pasteur.ac.ir."), [Reza Ahangari Cohan](https://pubmed.ncbi.nlm.nih.gov/?term=Cohan+RA&cauthor_id=42501767)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42501767/#full-view-affiliation-4 "Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran.") Affiliations Expand ### Affiliations * 1 Department of Biology, SR.C., Islamic Azad University, Tehran, Iran. * 2 National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran. Electronic address: M_farokhi@pasteur.ac.ir. * 3 Department of Hepatitis, AIDS and Blood-borne Diseases, Pasteur Institute of Iran, Tehran, Iran. Electronic address: A_bolhasani@pasteur.ac.ir. * 4 Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran. * PMID: **42501767** * DOI: [ 10.1016/j.ijpharm.2026.127223 ](https://doi.org/10.1016/j.ijpharm.2026.127223) Item in Clipboard # Development of HPV nanovaccine candidate based on IL-15-E7 fusion protein encapsulated in silk-fibroin nanoparticles Maryam Zeynali et al. Int J Pharm. 2026. Show details Display options Display options Format Abstract PubMed PMID Int J Pharm Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Int+J+Pharm%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Int+J+Pharm%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42501767/) . 2026 Sep 5:702:127223. doi: 10.1016/j.ijpharm.2026.127223. Epub 2026 Jul 25. ### Authors [Maryam Zeynali](https://pubmed.ncbi.nlm.nih.gov/?term=Zeynali+M&cauthor_id=42501767)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42501767/#short-view-affiliation-1 "Department of Biology, SR.C., Islamic Azad University, Tehran, Iran."), [Shiva Irani](https://pubmed.ncbi.nlm.nih.gov/?term=Irani+S&cauthor_id=42501767)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42501767/#short-view-affiliation-1 "Department of Biology, SR.C., Islamic Azad University, Tehran, Iran."), [Mehdi Farokhi](https://pubmed.ncbi.nlm.nih.gov/?term=Farokhi+M&cauthor_id=42501767)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42501767/#short-view-affiliation-2 "National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran. Electronic address: M_farokhi@pasteur.ac.ir."), [Azam Bolhassani](https://pubmed.ncbi.nlm.nih.gov/?term=Bolhassani+A&cauthor_id=42501767)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42501767/#short-view-affiliation-3 "Department of Hepatitis, AIDS and Blood-borne Diseases, Pasteur Institute of Iran, Tehran, Iran. Electronic address: A_bolhasani@pasteur.ac.ir."), [Reza Ahangari Cohan](https://pubmed.ncbi.nlm.nih.gov/?term=Cohan+RA&cauthor_id=42501767)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42501767/#short-view-affiliation-4 "Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran.") ### Affiliations * 1 Department of Biology, SR.C., Islamic Azad University, Tehran, Iran. * 2 National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran. Electronic address: M_farokhi@pasteur.ac.ir. * 3 Department of Hepatitis, AIDS and Blood-borne Diseases, Pasteur Institute of Iran, Tehran, Iran. Electronic address: A_bolhasani@pasteur.ac.ir. * 4 Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran. * PMID: **42501767** * DOI: [ 10.1016/j.ijpharm.2026.127223 ](https://doi.org/10.1016/j.ijpharm.2026.127223) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Human papillomavirus type 16 (HPV16) infections account for most cases of cervical cancer that occur throughout the world. The HPV E7 oncoprotein is known as a crucial target antigen for developing a therapeutic HPV vaccine. In this research, we designed a recombinant fusion protein comprising the IL-15 cytokine linked to HPV16 E7. This fusion protein was subsequently encapsulated in silk fibroin nanoparticles (SFNPs). The immune responses and antitumor effects of nanovaccine candidate were assessed in a tumor mouse model. Our data showed that the IL-15-E7 fusion protein-encapsulated SFNPs had a nano-sized structure (77.402 ± 7.852 nm) with a negative charge (-11.1 mV). Furthermore, the nanovaccine formulation induced higher IFN-γ and Granzyme B secretion than the recombinant IL-15-E7 fusion protein in mice. Compared to the recombinant IL-15-E7 fusion protein, the nanovaccine formulation showed a higher survival rate in a mouse tumor challenge (75% vs 50%), and a non-significant substantial tumor growth inhibition. In general, the IL-15-E7 fusion protein-encapsulated SFNPs significantly induced Th1 immunity, CTL activity, and anti-tumor effects, suggesting a promising nanovaccine candidate against HPV infections. **Keywords:** Cervical cancer; E7 oncoprotein; Human papillomavirus; Interleukin-15; Protein vaccine; Silk fibroin nanoparticles. Copyright © 2026 Elsevier B.V. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ Development of DNA Vaccine Targeting E6 and E7 Proteins of Human Papillomavirus 16 (HPV16) and HPV18 for Immunotherapy in Combination with Recombinant Vaccinia Boost and PD-1 Antibody. ](https://pubmed.ncbi.nlm.nih.gov/33468698/) Peng S, Ferrall L, Gaillard S, Wang C, Chi WY, Huang CH, Roden RBS, Wu TC, Chang YN, Hung CF.Peng S, et al.mBio. 2021 Jan 19;12(1):e03224-20. doi: 10.1128/mBio.03224-20.mBio. 2021.PMID: 33468698Free PMC article. * [ A novel recombinant protein vaccine containing the different E7 proteins of the HPV16, 18, 6, 11 E7 linked to the HIV-1 Tat (47-57) improve cytotoxic immune responses. ](https://pubmed.ncbi.nlm.nih.gov/34313864/) Mousavi T, Valadan R, Rafiei A, Abbasi A, Haghshenas MR.Mousavi T, et al.Biotechnol Lett. 2021 Sep;43(9):1933-1944. doi: 10.1007/s10529-021-03166-2. Epub 2021 Jul 27.Biotechnol Lett. 2021.PMID: 34313864 * [ HPV16 mutant E6/E7 construct is protective in mouse model. ](https://pubmed.ncbi.nlm.nih.gov/39350162/) Goodarzi MM, Mosayebi G, Ganji A, Raoufi E, Sadelaji S, Babaei S, Abtahi H.Goodarzi MM, et al.BMC Biotechnol. 2024 Sep 30;24(1):71. doi: 10.1186/s12896-024-00893-y.BMC Biotechnol. 2024.PMID: 39350162Free PMC article. * [ Self-amplifying mRNA nanovaccine encoding GM-CSF-fused HPV16 E7 enhances immunogenicity and therapeutic efficacy against cervical cancer. ](https://pubmed.ncbi.nlm.nih.gov/41224055/) Lin G, Guo X, Fu Z, Liu Z, Gu F, Yan H, Chen R, Liu Y, Kuang X, Xu Y, Zhang Y.Lin G, et al.Int J Biol Macromol. 2025 Dec;333(Pt 2):148933. doi: 10.1016/j.ijbiomac.2025.148933. Epub 2025 Nov 10.Int J Biol Macromol. 2025.PMID: 41224055 * [ In Silico Design and Immunological Studies of Two Novel Multiepitope DNA-Based Vaccine Candidates Against High-Risk Human Papillomaviruses. ](https://pubmed.ncbi.nlm.nih.gov/34308516/) Kayyal M, Bolhassani A, Noormohammadi Z, Sadeghizadeh M.Kayyal M, et al.Mol Biotechnol. 2021 Dec;63(12):1192-1222. doi: 10.1007/s12033-021-00374-z. 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