Transcutaneous immunization with a synthetic hexasaccharide-protein conjugate induces anti-Vibrio cholerae lipopolysaccharide responses in mice.
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.
Rollenhagen
Julianne E
JE
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA. julianne.rollenhagen@med.navy.mil
Kalsy
Anuj
A
Saksena
Rina
R
Sheikh
Alaullah
A
Alam
Mohammad Murshid
MM
Qadri
Firdausi
F
Calderwood
Stephen B
SB
Kovác
Pavol
P
Ryan
Edward T
ET
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000279:Administration, Cutaneous; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D002772:Cholera Toxin / Q000008:administration & dosage / Q000494:pharmacology; D022121:Cholera Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D019081:O Antigens / Q000737:chemistry / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000737:chemistry; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014734:Vibrio cholerae / Q000276:immunology*; D041241:Vibrio cholerae O1 / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D022121:Cholera Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D019081:O Antigens; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic; D012710:Serum Albumin, Bovine; D002772:Cholera Toxin