RESUMO
BACKGROUND: Studies of the immunogenicity of the killed bivalent whole cell oral cholera vaccine, Shanchol, have been performed in historically cholera-endemic areas of Asia. There is a need to assess the immunogenicity of the vaccine in Haiti and other populations without historical exposure to Vibrio cholerae. METHODOLOGY/PRINCIPAL FINDINGS: We measured immune responses after administration of Shanchol, in 25 adults, 51 older children (6-17 years), and 47 younger children (1-5 years) in Haiti, where cholera was introduced in 2010. A≥4-fold increase in vibriocidal antibody titer against V. cholerae O1 Ogawa was observed in 91% of adults, 74% of older children, and 73% of younger children after two doses of Shanchol; similar responses were observed against the Inaba serotype. A≥2-fold increase in serum O-antigen specific polysaccharide IgA antibody levels against V. cholerae O1 Ogawa was observed in 59% of adults, 45% of older children, and 61% of younger children; similar responses were observed against the Inaba serotype. We compared immune responses in Haitian individuals with age- and blood group-matched individuals from Bangladesh, a historically cholera-endemic area. The geometric mean vibriocidal titers after the first dose of vaccine were lower in Haitian than in Bangladeshi vaccinees. However, the mean vibriocidal titers did not differ between the two groups after the second dose of the vaccine. CONCLUSIONS/SIGNIFICANCE: A killed bivalent whole cell oral cholera vaccine, Shanchol, is highly immunogenic in Haitian adults and children. A two-dose regimen may be important in Haiti, and other populations lacking previous repeated exposures to V. cholerae.
Assuntos
Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Vibrio cholerae O139/imunologia , Vibrio cholerae O1/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Carga Bacteriana/efeitos dos fármacos , Criança , Pré-Escolar , Cólera/epidemiologia , Cólera/imunologia , Vacinas contra Cólera/administração & dosagem , Epidemias , Feminino , Haiti , Humanos , Lactente , Masculino , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Adulto JovemRESUMO
A live oral Vibrio cholerae O1 El Tor vaccine, Peru-15 was tested in a double-blind, randomized placebo controlled study for safety and immunogenicity in Phase I and Phase II studies in 240 Bangladeshi children aged 9 months-5 years of age. Two different doses (2x10(7) and 2x10(8)cfu) were tested. Vaccination did not elicit adverse events and the strain was genetically stable. Vibriocidal antibody responses developed in 42/50 (84%) toddlers (2-5 years) and 35/50 (70%) of younger children (9-23 months) and overall 77/100 (77%) who received the high dose. LPS-IgA-antibody responses were seen in 60% of toddlers and 34% of infants; 40% responded with IgA antibodies to cholera toxin. The responses to the reduced dose was lower. These studies demonstrate that Peru-15 at a dose of 2x10(8)cfu is safe and immunogenic in children in Bangladesh.
Assuntos
Vacinas contra Cólera/imunologia , Administração Oral , Anticorpos Antivirais/sangue , Pré-Escolar , Vacinas contra Cólera/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Imunoglobulina A/sangue , Lactente , Lipopolissacarídeos/imunologia , Masculino , Vacinas Atenuadas/imunologiaRESUMO
BACKGROUND: A live oral Vibrio cholerae O1 El Tor vaccine candidate, Peru-15, was studied for safety, immunogenicity, and excretion in phase 1 (inpatient) and phase 2 (outpatient) studies of Bangladeshi adults.METHODs. The study was conducted among adults, by use of a double-blind, randomized, placebo-controlled design. A single dose of Peru-15 (approximately 2 x 108 cfu) or placebo (buffer only) was given in standard bicarbonate and ascorbic acid buffer.RESULTS. Study treatment did not elicit any major adverse events in the volunteers, during either the inpatient or the outpatient phases, and there were no reports of diarrhea. V. cholerae was isolated from the stool of only 1 volunteer and was found to be genetically identical to the vaccine strain. Vibriocidal antibody responses were seen in 30 (75%) of 40 vaccine recipients and in 3 (10%) of 30 placebo recipients. Peripheral blood immunoglobulin (Ig) A and IgM antibody-secreting cell responses to lipopolysaccharide were seen in the majority of vaccine recipients (response rate, 78%--88%). Seroconversion for lipopolysaccharide-specific IgA antibodies was seen in 88% of vaccine recipients. The response in vaccine recipients was significantly higher than that in placebo recipients, in all of the immunological assays (P=.036 to <.001). A lower immunological response against cholera toxin B subunit was detected.CONCLUSIONS. The safety and immunogenicity of this Peru-15 vaccine candidate indicates the usefulness of future studies in Bangladesh, where cholera is endemic.