Rotavirus vp7 antigen produced by Lactococcus lactis induces neutralizing antibodies in mice

Abstract

C . A . P E R E Z , C . E I C H W A L D , O . B U R R O N E A N D D . D E M E N D O Z A . 2005.Aims: To determine if live recombinant Lactococcus lactis strains expressing rotavirus VP7 antigen are immunogenic in mice. Methods and Results: Using the food-grade lactic acid bacterium L. lactis as a carrier, we expressed VP7, the major rotavirus outer shell protein and one of the main components of the infective particle, as a cytoplasmic, secreted or cell wall anchored forms. Our results showed that recombinant L. lactis strains secreting VP7 proved to be more immunogenic than strains containing the antigen in the cytoplasm or anchored to the cell wall. Conclusions: This is the first demonstration that recombinant L. lactis producing VP7 can induce the production of a neutralizing antibody response against rotavirus by the intragastric route. Significance and Impact of the Study: Rotaviruses are the single most important aetiological agents of severe diarrhoea of infants and young children worldwide and have been estimated to be responsible for 650 000-800 000 deaths per year of children younger than 5 years old in development countries. Thus, the development of a safe and effective vaccine has been a global public health goal. Although two of five mice orally inoculated with L. lactis strains secreting VP7 elicited a specific-antibody response, these strains could be very useful to be used as a prototype to develop a new generation of protective rotavirus vaccines.

Lactococcus lactis as a Cell Factory for Delivery of Therapeutic Proteins

“…L. lactis expressing cell wallanchored Rotavirus VP7 has also been investigated as an oral vaccine candidate. However, when sera from individually immunized mice were examined only 3 out of 10 sera showed specific reactivity with VP7 [22]. Finally recent work has demonstrated that L. lactis expressing domain III of the major dengue virus envelope protein E (EDIII) may provide a successful vaccine platform when administered either orally or intranasally, although results varied between mouse strains used [23].…”

Development of a Bacillus subtilis -Based Rotavirus Vaccine

“…(B) Protection against rotavirus challenge. The immunized mice were challenged (by oral gavage) with 100 ID 50 per mouse with a murine strain (EDIM EW) rotavirus 3 weeks after the final immunization. Virus shedding in feces, as determined by an ELISA for detecting rotavirus antigen, is given as A 450 values Ϯ standard errors of the means (SEM).…”

“…Oral immunization with recombinants of either Salmonella enterica serovar Typhimurium or Lactobacillus lactis expressing rotavirus virion protein 7 (VP7) generated immune responses after oral administration to mice, but no challenge studies were reported (50,58).…”

Lactococcus lactis as a vehicle for the heterologous expression of fungal ribotoxin variants with reduced IgE-binding affinity

“…However, genetically modified versions of this microorganism are still effective in delivering antigens to the mucosal immune system and capable of inducing a local immune response (Robinson et al, 1997;Maassen et al, 1999;AdelPatient et al, 2005;Perez et al, 2005). This seems to happen because L. lactis lacks the ability to multiply in vivo but it can readily be sampled by dendritic cells.…”