RESUMO
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.
Assuntos
Antígenos de Bactérias/imunologia , Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Oligossacarídeos/imunologia , Vibrio cholerae O1/imunologia , Adjuvantes Imunológicos/administração & dosagem , Administração Cutânea , Administração Oral , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/administração & dosagem , Toxinas Bacterianas/administração & dosagem , Atividade Bactericida do Sangue , Cólera/imunologia , Toxina da Cólera/administração & dosagem , Vacinas contra Cólera/administração & dosagem , Modelos Animais de Doenças , Enterotoxinas/administração & dosagem , Proteínas de Escherichia coli/administração & dosagem , Fezes/química , Feminino , Imunização Secundária/métodos , Imunoglobulina A/análise , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Injeções Subcutâneas , Camundongos , Oligossacarídeos/administração & dosagem , Análise de Sobrevida , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologiaRESUMO
To evaluate the probiotic, Bifidobacterium breve strain Yakult (BBG-01), for safety and enhancement of immunogenicity in an oral inactivated cholera vaccine, a randomized double-blind placebo-controlled study was performed. Bangladeshi children under 5-year-old received BBG-01 or placebo for 4 weeks with two doses of oral cholera vaccine. Serum/fecal antibodies and fecal bacterial flora in the study participants were monitored. All adverse events were mild and transient and had no significant difference between the two groups. Immunological responses were similar comparing the two groups. A negative correlation between Bifidobacterium and Enterobacteriaceae in the probiotic group suggests a possible involvement of BBG-01 in alteration of the enteric bacterial flora. In conclusion, BBG-01 is well tolerated by Bangladeshi children although the post vaccinal immunostimulatory effect of BBG-01 was not evident.