Induction of neutralizing antibodies against dengue virus type 2 upon mucosal administration of a recombinant Lactococcus lactis strain expressing envelope domain III antigen

Mucosal vaccines present several advantages over conventional parenteral vaccines including their ease of administration and low cost, both criteria being priorities for developing countries plagued by infectious diseases. A recombinant Lactococcus lactis strain producing the envelope domain III (EDIII) antigen from dengue virus serotype 2 was engineered, and the ability of the live recombinant bacteria to trigger a systemic anti-EDIII IgG antibody response upon nasal or oral administration to BALB/c and C57BL/6 mice was investigated. Results showed that the antibody response depended on the route of administration and on the mouse strain inoculated. Out of six, two and three C57BL/6 mice orally and nasally inoculated with the recombinant bacteria, respectively, displayed anti-EDIII antibody responses higher than that obtained in the mouse group intraperitoneally (i.p.) immunized with heat-inactivated dengue 2 virus. The protective potential of the immune sera was measured using the plaque reduction neutralizing test (PRNT) and results indicated that high anti-EDIII antibody levels did not correlate directly with high neutralizing activities. Immune sera from orally inoculated mice were found the most potent to neutralize in vitro dengue infection with neutralizing antibody activities in some cases higher than that obtained with the immune sera from mice i.p. injected with heat-inactivated virus.