Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection

Ingrid S Ganda; Qian Zhong; Mirabela Hali; Ricardo L C Albuquerque; Francine F Padilha; Sandro R P da Rocha; Judith A Whittum-Hudson

doi:10.1016/j.ijpharm.2017.05.045

Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection

Int J Pharm. 2017 Jul 15;527(1-2):79-91. doi: 10.1016/j.ijpharm.2017.05.045. Epub 2017 May 22.

Authors

Ingrid S Ganda¹, Qian Zhong², Mirabela Hali³, Ricardo L C Albuquerque⁴, Francine F Padilha⁵, Sandro R P da Rocha⁶, Judith A Whittum-Hudson⁷

Affiliations

¹ Biomaterials Laboratory, Technology and Research Institute, Tiradentes University, Aracaju, SE, 49032-490, Brazil; Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI 48202, USA; Departments of Immunology and Microbiology, Internal Medicine (Rheumatology), and Ophthalmology, School of Medicine, Wayne State University, Detroit, MI 48201, USA. Electronic address: ingrid.ganda@gmail.com.
² Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI 48202, USA. Electronic address: qzhong@stanford.edu.
³ Departments of Immunology and Microbiology, Internal Medicine (Rheumatology), and Ophthalmology, School of Medicine, Wayne State University, Detroit, MI 48201, USA. Electronic address: mhali@med.wayne.edu.
⁴ Laboratory of Morphology and Structural Biology, Technology and Research Institute, Tiradentes University, Aracaju, SE, 49032-490, Brazil. Electronic address: ricardo.patologia@uol.com.br.
⁵ Biomaterials Laboratory, Technology and Research Institute, Tiradentes University, Aracaju, SE, 49032-490, Brazil. Electronic address: fpadilha@yahoo.com.
⁶ Biomaterials Laboratory, Technology and Research Institute, Tiradentes University, Aracaju, SE, 49032-490, Brazil; Department of Chemical Engineering and Materials Science, Wayne State University, Detroit, MI 48202, USA. Electronic address: srdarocha@vcu.edu.
⁷ Departments of Immunology and Microbiology, Internal Medicine (Rheumatology), and Ophthalmology, School of Medicine, Wayne State University, Detroit, MI 48201, USA. Electronic address: jhudson@med.wayne.edu.

Abstract

Peptide-based vaccines have emerged in recent years as promising candidates in the prevention of infectious diseases. However, there are many challenges to maintaining in vivo peptide stability and enhancement of peptide immunogenicity to generate protective immunity which enhances clearance of infections. Here, a dendrimer-based carrier system is proposed for peptide-based vaccine delivery, and shows its anti-microbial feasibility in a mouse model of Chlamydia trachomatis. Chlamydiae are the most prevalent sexually transmitted bacteria worldwide, and also the causal agent of trachoma, the leading cause of preventable infectious blindness. In spite of the prevalence of this infectious agent and the many previous vaccine-related studies, there is no vaccine commercially available. The carrier system proposed consists of generation 4, hydroxyl-terminated, polyamidoamine (PAMAM) dendrimers (G4OH), to which a peptide mimic of a chlamydial glycolipid antigen-Peptide 4 (Pep4, AFPQFRSATLLL) was conjugated through an ester bond. The ester bond between G4OH and Pep4 is expected to break down mainly in the intracellular environment for antigen presentation. Pep4 conjugated to dendrimer induced Chlamydia-specific serum antibodies after subcutaneous immunizations. Further, this new vaccine formulation significantly protected immunized animals from vaginal challenge with infectious Chlamydia trachomatis, and it reduced infectious loads and tissue (genital tract) damage. Pep4 conjugated to G4OH or only mixed with peptide provided enhanced protection compared to Pep4 and adjuvant (i.e. alum), suggesting a potential adjuvant effect of the PAMAM dendrimer. Combined, these results demonstrate that hydroxyl-terminated PAMAM dendrimer is a promising polymeric nanocarrier platform for the delivery of peptide vaccines and this approach has potential to be expanded to other infectious intracellular bacteria and viruses of public health significance.

Keywords: Chlamydia trachomatis; Infectious disease; Nanovaccine; PAMAM dendrimer; Subunit peptide vaccine.

MeSH terms

Animals
Bacterial Vaccines / administration & dosage*
Chlamydia Infections / therapy*
Chlamydia trachomatis
Dendrimers / chemistry*
Female
Mice, Inbred BALB C
Vaccines, Subunit / administration & dosage

Substances

Bacterial Vaccines
Dendrimers
PAMAM Starburst
Vaccines, Subunit

Grants and funding

R01 AI080928/AI/NIAID NIH HHS/United States