A Lactic Acid Bacteria (LAB)-Based Vaccine Candidate for Human Norovirus

Area of Science:

• Virology
• Immunology
• Microbiology

Background:

• Human noroviruses (HuNoVs) cause widespread acute gastroenteritis, with no current FDA-approved vaccine.
• Challenges in HuNoV vaccine development include the lack of efficient cell culture and small animal models.

Purpose of the Study:

• To develop and evaluate a novel vaccine vector using lactic acid bacteria (LAB) for delivering HuNoV antigens.
• To assess the immunogenicity and protective efficacy of a LAB-based HuNoV vaccine candidate in a gnotobiotic piglet model.

Main Methods:

• Constructed a Lactococcus lactis strain (LAB-VP1) expressing the VP1 gene of HuNoV GII.4.
• Administered LAB-VP1 orally to gnotobiotic piglets and monitored persistence, immune response (IgG, IgA), and protection against HuNoV challenge.
• Detected LAB DNA and HuNoV VP1 antigen in tissues and analyzed immune markers in serum and feces.

Main Results:

• HuNoV VP1 protein was highly expressed and secreted by the LAB vector.
• LAB-VP1 administration led to persistent colonization in the piglet intestine and systemic detection of LAB DNA and VP1.
• HuNoV-specific IgG and IgA antibodies were induced, and immunized piglets showed significantly reduced viral antigen levels after challenge compared to controls.

Conclusions:

• Lactic acid bacteria serve as an effective delivery vector for HuNoV antigens.
• A LAB-based HuNoV vaccine candidate demonstrates immunogenicity and confers protective immunity in a gnotobiotic piglet model.
• This study presents a promising new strategy for developing a vaccine against human norovirus gastroenteritis.