Induction of Protective Immunity by SyntheticVibrio choleraeHexasaccharide Derived fromV. choleraeO1 Ogawa Lipopolysaccharide Bound to a Protein Carrier

Abstract

Synthetic antigens that mimic the terminal hexasaccharide epitope of the O-specific polysaccharide of Vibrio cholerae O1, serotype Ogawa, were conjugated to bovine serum albumin (BSA). Conjugates with carbohydrate-to-carrier molar ratios of 15.5:1, 9.2:1, and 4.6:1 were tested for immunogenicity and efficacy in mice. The role of preimmunity to BSA and the use of adjuvant in the generation of the serologic response to the O-specific polysaccharide and protection against virulent V. cholerae was examined. Preimmunity to BSA did not affect the anti-Ogawa titers but seemed to enhance the protective capacity of antiserum. All 3 conjugates were immunogenic, but adjuvant was effective at inducing higher and earlier antibody responses. In tertiary serum samples, a correlation was found between vibriocidal activity and protection. The protective capacity of antiserum was evident in serum from mice immunized with all conjugates, but it was highest in the groups that received the conjugate with the lowest level of substitution. Further studies are required to increase understanding of the reason for differential protection.

TcpF Is a Soluble Colonization Factor and Protective Antigen Secreted by El Tor and Classical O1 and O139 Vibrio cholerae Serogroups

“…These acellular vaccines were introduced into clinical practice in the United States in 1991 as the fourth and fifth doses of a five-dose series and were approved for use in the primary series in 1996 as part of the diphtheriatetanus-acellular pertussis combination vaccine. In addition to reducing the number of adverse events associated with pertussis vaccination, these formulations also proved to be at least as protective as their whole-cell predecessor (7,(12)(13)(14)(15)28). Recent studies have demonstrated that humans are capable of mounting an immune response to TcpF during V. cholerae infection, further validating the hypothesis that TcpF is a viable option for inclusion in a multisubunit cholera vaccine (16).…”

“…These results may have been in part related to differential expression of antigens that engender protective immunity. Several studies have documented the efficacy of antibodies directed against V. cholerae subunits (TcpA and lipopolysaccharide) for protection from disease in the infant mouse cholera model (7,28,38,39,52). Subunit vaccines may prove to be superior to whole-cell live vaccines since the appropriate antigens can reliably be introduced into each individual at the appropriate dose.…”

“…Based on the results presented here, we propose that TcpF may be a reasonable antigen to include in a polyvalent subunit vaccine formulation. Combined with antilipopolysaccharide and anti-TCP responses, antibodies directed against TcpF may potently inhibit colonization in the human intestine, thereby preventing disease (7,52). Furthermore, if antigens representing proteins involved in each step of the colonization process are combined into a vaccine formulation, a higher degree of protection may be provided than that obtained with a single subunit or with multiple subunits, each of which is a portion of proteins involved in the same step of colonization.…”

Characterization of a novel protective monoclonal antibody that recognizes an epitope common to Vibrio cholerae Ogawa and Inaba serotypes

“…In order to overcome the problems associated with LPS, synthetic O-SP sugar components can be conjugated to protein carriers (neoglycoconjugates) to recruit T cells. Although Ogawa neoglycoconjugates induced protective antibodies in mice (Chernyak et al, 2002), Inaba neoglycoconjugates induced only low-affinity antibodies that were not protective. This may be due to low intrinsic affinity of the epitope for Inaba-specific B-cell receptor.…”

Transcutaneous Immunization with Toxin-Coregulated Pilin A Induces Protective Immunity against Vibrio cholerae O1 El Tor Challenge in Mice

“…Of note, Wu et al (42) also found protection to occur in offspring of dams immunized parenterally with a TcpA pilin peptide polymer and adjuvant, although there were measurable IgA responses in vaccinated dams in this experiment. Also, a number of researchers have assayed protection in neonatal mice by using passively administered convalescent-phase sera from immunized and unrelated adult mice (the neonates were, therefore, not ingesting breast milk of immunized dams, suggesting that protection was present in the serum fraction) (2,5). In the latter experiments, convalescent-phase sera of immunized animals were mixed with the V. cholerae challenge inoculum prior to oral administration to neonates.…”