Format

Send to

Choose Destination
Vaccine. 2019 Mar 14;37(12):1674-1684. doi: 10.1016/j.vaccine.2019.01.056. Epub 2019 Feb 14.

Hepatitis B virus-like particles expressing Plasmodium falciparum epitopes induce complement-fixing antibodies against the circumsporozoite protein.

Author information

1
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia; School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.
2
Burnet Institute, Commercial Road, Melbourne, Victoria 3004, Australia; Department of Immunology and Pathology, Monash University, Melbourne, Victoria 2004, Australia.
3
Victorian Infectious Diseases Reference Laboratory (VIDRL), Melbourne Health, The Peter Doherty Institute, Melbourne, Victoria 3000, Australia.
4
Royal Melbourne Institute of Technology (RMIT) University, School of Science, Melbourne, Victoria 3001, Australia; Commonwealth Scientific and Industrial Research Organisation, Clayton, Victoria 3169, Australia.
5
Commonwealth Scientific and Industrial Research Organisation, Clayton, Victoria 3169, Australia.
6
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia; Burnet Institute, Commercial Road, Melbourne, Victoria 3004, Australia; Department of Immunology and Pathology, Monash University, Melbourne, Victoria 2004, Australia; Department of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia.
7
Victorian Infectious Diseases Reference Laboratory (VIDRL), Melbourne Health, The Peter Doherty Institute, Melbourne, Victoria 3000, Australia; Royal Melbourne Institute of Technology (RMIT) University, School of Science, Melbourne, Victoria 3001, Australia. Electronic address: hans.netter@mh.org.au.

Abstract

The repetitive structure of compact virus-like particles (VLPs) provides high density displays of antigenic sequences, which trigger key parts of the immune system. The hepatitis B virus (HBV) and human papilloma virus (HPV) vaccines exploit the assembly competence of structural proteins, which are the effective immunogenic components of the prophylactic HBV and HPV vaccines, respectively. To optimize vaccine designs and to promote immune responses against protective epitopes, the "Asp-Ala-Asp-Pro" (NANP)-repeat from the Plasmodium falciparum circumsporozoite protein (CSP) was expressed within the exposed, main antigenic site of the small HBV envelope protein (HBsAgS); this differs from the RTS,S vaccine, in which CSP epitopes are fused to the N-terminus of HBsAgS. The chimeric HBsAgS proteins are assembly competent, produce VLPs, and provide a high antigenic density of the NANP repeat sequence. Chimeric VLPs with four or nine NANP-repeats (NANP4 and NANP9, respectively) were expressed in mammalian cells, the HBsAgS- and CSP-specific antigenicity of the VLPs was determined, and the immunogenicity of the VLPs assessed in relation to the induction of anti-HBsAgS and anti-CSP antibody responses. The chimeric VLPs induced high anti-CSP titres in BALB/c mice independent of the number of the NANP repeats. However, the number of NANP repeats influenced the activity of vaccine-induced antibodies measured by complement fixation to CSP, one of the proposed effector mechanisms for Plasmodium neutralization in vivo. Sera from mice immunized with VLPs containing nine NANP repeats performed better in the complement fixation assay than the group with four NANP repeats. The effect of the epitope-specific density on the antibody quality may instruct VLP platform designs to optimize immunological outcomes and vaccine efficacy.

KEYWORDS:

Epitope repeats; Hepatitis B surface antigen; Plasmodium falciparum; Virus-like particle (VLP)

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center