A shortcoming of currently available oral cholera vaccines is their induction of relatively short-term protection against cholera compared to that afforded by wild-type disease. We were interested in whether transcutaneous or subcutaneous boosting using a neoglycoconjugate vaccine made from a synthetic terminal hexasaccharide of the O-specific polysaccharide of Vibrio cholerae O1 (Ogawa) coupled to bovine serum albumin as a carrier (CHO-BSA) could boost lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result in protective immunity following oral priming immunization with whole-cell cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative cholera toxin (CT) or Escherichia coli heat-labile toxin (LT) following oral priming with attenuated V. cholerae O1 vaccine strain O395-NT resulted in significant increases in serum anti-V. cholerae LPS IgG, IgM, and IgA (P<0.01) responses as well as in anti-Ogawa (P<0.01) and anti-Inaba (P<0.05) vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced by transcutaneous (P<0.01) but not subcutaneous immunization. Immune responses following use of CT or LT as an adjuvant were comparable. In a neonatal mouse challenge assay, immune serum from boosted mice was associated with 79% protective efficacy against death. Our results suggest that transcutaneous and subcutaneous boosting with a neoglycoconjugate following oral cholera vaccination may be an effective strategy to prolong protective immune responses against V. cholerae. Copyright

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doi.org/10.1128/CVI.05689-11, hdl.handle.net/1765/39112
Clinical and Vaccine Immunology (Print)
Erasmus MC: University Medical Center Rotterdam

Tarique, A. A., Kalsy, A., Arifuzzaman, M., Rollins, S. M., Charles, R. C., Leung, D. T., … Ryan, E. T. (2012). Transcutaneous immunization with a Vibrio cholerae O1 Ogawa synthetic hexasaccharide conjugate following oral whole-cell cholera vaccination boosts vibriocidal responses and induces protective immunity in mice. Clinical and Vaccine Immunology (Print), 19(4), 594–602. doi:10.1128/CVI.05689-11