Title:Heterologous Prime-boost Vaccination Using Adenovirus and Albumin
Nanoparticles as Carriers for Human Papillomavirus 16 E7 Epitope
Volume: 24
Issue: 9
Author(s): Momeneh Ghanaat, Hami Kaboosi*, Babak Negahdari*, Esmail Fattahi and Ziba Veisi Malekshahi
Affiliation:
- Department of Microbiology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran
- Department of Medical
Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
Keywords:
Nanocarriers, immunotherapy, adenovirus, albumin, nanoparticle, epitope.
Abstract:
Background: Nanocarriers are these days considered an attractive approach in cancer
immunotherapy owing to their ability to deliver antigens to antigen-presenting cells (APCs) for
stimulating robust immune cells against the tumor.
Objectives: The objective of this study was to construct nanocomplexes using two nanocarriers with
negative surface charge, adenovirus (Ad) and human serum albumin nanoparticle (HSA-NP), and
coat their surface with a modified and positively-charged HPV16 E7 MHC-I specific epitope to assess
their anti-tumor effects in a TC-1 mouse model.
Methods: After the construction of Ad and HSA-NP, their complexes with HPV16 E7 MHC-I specific
epitope were characterized by zeta potential and dynamic light scattering. Then, the cellular
immunity and CTL responses in immunized mice were assessed by measuring the levels of IL-10
and IFN-γ and the expression of CD107a, a marker of CTL response, as well as tumor inhibition.
Results: The zeta potential and dynamic light scattering results showed that incubation of the oppositely-
charged nanocarriers and MHC-I specific epitope led to the formation of nanocomplexes in
which the surface charge of nanocarriers was changed from negative to positive with minimal
changes in the particle size. We demonstrated that the nanocomplex platforms in heterologous primeboost
regimens generate significantly higher E7-specific IL-10, IFN-γ, and CTL responses. Moreover,
the heterologous nanocomplex regimens, Alb/Pep-Ad/Pep and Ad/Pep-Alb/Pep, significantly
suppressed the growth of TC-1 tumors in vivo compared with mice receiving homologous regimens
and naked nanocarriers.
Conclusion: The heterologous nanocomplexes might serve as an effective vaccine strategy against
HPV-induced cervical cancer.