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Updated: Aug 28, 2025
Expression and Purification of Virus-like Particles for Vaccination
Published on: June 2, 2016
Safety and immunogenicity of parvovirus B19 virus-like particle vaccine lacking phospholipase A2 activity
Hidehiko Suzuki1, Takafumi Noguchi1, Noriko Matsugu2
1Virus vaccine group, BIKEN Innovative Vaccine Research Alliance Laboratories, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Osaka, Japan; The Research Foundation for Microbial Diseases of Osaka University, Suita, Osaka, Japan.
Insights
A new Parvovirus B19 (B19) vaccine candidate, the ⊿PLA2 B19 VLP, shows promise. This modified virus-like particle (VLP) lacks inflammatory activity and effectively induces neutralizing antibodies, suggesting a safer B19 vaccine.
Area of Science:
- Virology and Immunology
- Vaccine Development
Background:
- Parvovirus B19 (B19) causes fifth disease and severe fetal complications like hydrops fetalis.
- Current B19 virus-like particle (VLP) vaccine candidates face challenges, partly due to the inflammatory B19 phospholipase A2 (PLA2) domain.
- Previous B19 VLP vaccine strategies involved mutations to reduce PLA2 activity.
Purpose of the Study:
- To design and evaluate a novel B19 VLP vaccine candidate lacking PLA2 activity.
- To assess the immunogenicity and safety of the ⊿PLA2 B19 VLP in vivo.
- To investigate the role of the B19 PLA2 domain in immune responses.
Main Methods:
- Development of a deletion mutant VLP (⊿PLA2 B19 VLP) lacking PLA2 activity.
- In vivo immunization studies in mice to assess immunogenicity and inflammatory responses.
- Analysis of CD4+ T cell activation and antibody neutralization in vaccinated mice and human samples.
Main Results:
- The ⊿PLA2 B19 VLP demonstrated no histological inflammatory reactions or IL-6 production.
- B19 PLA2 stimulation did not activate CD4+ T cells from vaccinated mice or B19-seropositive humans.
- ⊿PLA2 B19 VLPs induced neutralizing antibodies against B19, comparable to levels in B19-seropositive individuals.
Conclusions:
- The ⊿PLA2 B19 VLP is a safe and immunogenic vaccine candidate.
- The B19 PLA2 domain is not a critical CD4+ T cell epitope for neutralizing antibody induction.
- This modified VLP represents a promising strategy for developing an effective B19 vaccine.
Abstract:
Parvovirus B19 (B19) belongs to the Erythroparvovirus genus and is known to cause the fifth disease in children. Primary infection of pregnant women is associated with a high risk of hydrops fetalis and stillbirth due to severe fetal anemia. Virus-like particle (VLP) vaccine candidates for B19 have been developed, although none have been approved so far. The B19 phospholipase A2 domain (B19 PLA2), located in the VP1 unique region, is believed to be associated with adverse inflammatory reactions, and previous effective attempts to improve this vaccine modality inserted a mutation to impair the PLA2 activity of VLPs. In this study, we designed VLPs with a deletion mutant of PLA2 (⊿PLA2 B19 VLP), devoid of PLA2 activity, and confirmed their immunogenicity and safe use in vivo. These results were supported by the lack of histological inflammatory reactions at the site of immunization or the production of IL-6 in ⊿PLA2 B19 VLP-immunized mice, that were observed in mice immunized with B19 VLPs. CD4+ T cells from mice vaccinated with VLPs and B19-seropositive human samples were not activated by B19 PLA2 stimulation, suggesting that the B19 PLA2 domain does not constitute a major CD4+ T cell epitope. Most importantly, the ⊿PLA2 B19 VLPs induced neutralizing antibodies against B19, in levels similar to those found in B19-seropositive human samples, indicating that they could be used as a safe and effective vaccine candidate against B19.
