TY - JOUR
T1 - Transcutaneous immunization with a synthetic hexasaccharide-protein conjugate induces anti-Vibrio cholerae lipopolysaccharide responses in mice
AU - Rollenhagen, Julianne E.
AU - Kalsy, Anuj
AU - Saksena, Rina
AU - Sheikh, Alaullah
AU - Alam, Mohammad Murshid
AU - Qadri, Firdausi
AU - Calderwood, Stephen B.
AU - Kovác, Pavol
AU - Ryan, Edward T.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health, including the National Institute of Allergy & Infectious Diseases (AI067342 [ETR], AI40725 [ETR]. AI058935 [SBC]), and a Training Grant in Vaccine Development from the Fogarty International Center (TW05572 [AS, FQ]). The authors would like to thank William F. Wade for helpful input.
PY - 2009/8/6
Y1 - 2009/8/6
N2 - Antibodies specific for Vibrio cholerae lipopolysaccaride (LPS) are common in humans recovering from cholera, and constitute a primary component of the vibriocidal response, a serum complement-mediated bacteriocidal response correlated with protection against cholera. In order to determine whether transcutaneous immunization (TCI) with a V. cholerae neoglycoconjugate (CHO-BSA) comprised of a synthetic terminal hexasaccharide of the O-specific polysaccharide of V. cholerae O1 (Ogawa) conjugated with bovine serum albumin (BSA) could induce anti-V. cholerae LPS and vibriocidal responses, we applied CHO-BSA transcutaneously in the presence or absence of the immune adjuvant cholera toxin (CT) to mice. Transcutaneously applied neoglycoconjugate elicited prominent V. cholerae specific LPS IgG responses in the presence of CT, but not IgM or IgA responses. CT applied on the skin induced strong IgG and IgA serum responses. TCI with neoglycoconjugate did not elicit detectable vibriocidal responses, protection in a mouse challenge assay, or stool anti-V. cholerae IgA responses, irrespective of the presence or absence of CT. Our results suggest that transcutaneously applied synthetic V. cholerae neoglycoconjugate is safe and immunogenic, but predominantly induces systemic LPS responses of the IgG isotype.
AB - Antibodies specific for Vibrio cholerae lipopolysaccaride (LPS) are common in humans recovering from cholera, and constitute a primary component of the vibriocidal response, a serum complement-mediated bacteriocidal response correlated with protection against cholera. In order to determine whether transcutaneous immunization (TCI) with a V. cholerae neoglycoconjugate (CHO-BSA) comprised of a synthetic terminal hexasaccharide of the O-specific polysaccharide of V. cholerae O1 (Ogawa) conjugated with bovine serum albumin (BSA) could induce anti-V. cholerae LPS and vibriocidal responses, we applied CHO-BSA transcutaneously in the presence or absence of the immune adjuvant cholera toxin (CT) to mice. Transcutaneously applied neoglycoconjugate elicited prominent V. cholerae specific LPS IgG responses in the presence of CT, but not IgM or IgA responses. CT applied on the skin induced strong IgG and IgA serum responses. TCI with neoglycoconjugate did not elicit detectable vibriocidal responses, protection in a mouse challenge assay, or stool anti-V. cholerae IgA responses, irrespective of the presence or absence of CT. Our results suggest that transcutaneously applied synthetic V. cholerae neoglycoconjugate is safe and immunogenic, but predominantly induces systemic LPS responses of the IgG isotype.
KW - Cholera
KW - Conjugate
KW - Transcutaneous immunization
UR - http://www.scopus.com/inward/record.url?scp=67650488583&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2009.06.040
DO - 10.1016/j.vaccine.2009.06.040
M3 - Article
C2 - 19563890
AN - SCOPUS:67650488583
SN - 0264-410X
VL - 27
SP - 4917
EP - 4922
JO - Vaccine
JF - Vaccine
IS - 36
ER -