Oral administration of a chimeric Hepatitis B Virus S/preS1 antigen produced in lettuce triggers infection neutralizing antibodies in mice

Vaccine. 2018 Sep 11;36(38):5789-5795. doi: 10.1016/j.vaccine.2018.07.072. Epub 2018 Aug 3.


Hepatitis B Virus (HBV) infection can be prevented by vaccination. Vaccines containing the small (S) envelope protein are currently used in universal vaccination programs and achieve protective immune response in more than 90% of recipients. However, new vaccination strategies are necessary for successful immunization of the remaining non- or low-responders. We have previously characterized a novel HBV chimeric antigen, which combines neutralization epitopes of the S and the preS1 domain of the large (L) envelope protein (genotype D). The S/preS121-47 chimera produced in mammalian cells and Nicotiana benthamiana plants, induced a significantly stronger immune response in parenterally vaccinated mice than the S protein. Here we describe the transient expression of the S/preS121-47 antigen in an edible plant, Lactuca sativa, for potential development of an oral HBV vaccine. Our study shows that oral administration of adjuvant-free Lactuca sativa expressing the S/preS121-47 antigen, three times, at 1 μg/dose, was sufficient to trigger a humoral immune response in mice. Importantly, the elicited antibodies were able to neutralize HBV infection in an NTCP-expressing infection system (HepG2-NTCP cell line) more efficiently than those induced by mice fed on Lactuca sativa expressing the S protein. These results support the S/preS121-47 antigen as a promising candidate for future development as an edible HBV vaccine.

Keywords: Edible vaccine; Hepatitis B Virus; Neutralizing antibody; Plant expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood*
  • Cell Line, Tumor
  • Female
  • Hep G2 Cells
  • Hepatitis B / prevention & control*
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B Vaccines / administration & dosage
  • Hepatitis B Vaccines / immunology*
  • Hepatitis B virus / immunology*
  • Humans
  • Lettuce / genetics
  • Lettuce / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Protein Precursors / immunology*
  • Recombinant Fusion Proteins / immunology
  • Vaccination
  • Viral Envelope Proteins / immunology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Protein Precursors
  • Recombinant Fusion Proteins
  • Viral Envelope Proteins
  • presurface protein 1, hepatitis B surface antigen