Oral vaccination via virus-like particles encapsulated in Lactococcus lactis.

2026-02
Fish & shellfish immunology 169

PubMed: 41519596
DOI: 10.1016/j.fsi.2025.111013

Study Design

Type: Clinical Trial
Population: Asian seabass (Lates calcarifer) fingerlings
Methods: NNV capsid protein was expressed in Lactococcus lactis and evaluated as a vaccine candidate; intraperitoneal injection of purified VLPs and oral vaccination with VLPs encapsulated in live, heat-inactivated, or sodium hypochlorite-inactivated L. lactis cells

Animal Study

Nervous necrosis virus (NNV) causes severe disease in marine fish, leading to high mortality and significant economic losses in aquaculture. Effective oral vaccines are urgently needed for large-scale, labour-efficient immunization of farmed fish. In this study, NNV capsid protein was successfully expressed in Lactococcus lactis (L. lactis) and evaluated as a vaccine candidate in Asian seabass (Lates calcarifer) fingerlings. The capsid protein assembled into virus-like particles (VLPs), structurally similar to those produced in E. coli. Intraperitoneal injection of purified VLPs elicited strong humoral immunity, with NNV-specific IgM titers four-fold higher than oral delivery, despite a tenfold lower antigen dose. However, encapsulation of VLPs in live or heat-inactivated L. lactis cells failed to induce protective immunity through oral delivery, likely due to poor antigen release. In contrast, sodium hypochlorite-inactivated L. lactis preserved VLP encapsulation, solubility and structural integrity, and oral vaccination with these cells induced approximately two-fold higher antibody and neutralizing titers than the purified VLPs. Challenge studies demonstrated a significant ∼2.5-log reduction in brain viral load 7 days post-challenge. Overall, these findings highlight hypochlorite-inactivated L. lactis as a promising oral vaccine platform, offering a sustainable strategy for aquaculture immunization against NNV.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactococcus lactis	—	Improved Specific Antibody Response	Beneficial	Moderate	View source oral vaccination with these cells induced approximately two-fold higher antibody and neutralizing titers than the purified VLPs
Lactococcus lactis	—	Reduced Viral Load	Beneficial	Large	View source Challenge studies demonstrated a significant ∼2.5-log reduction in brain viral load 7 days post-challenge