Adjuvant Principle of Pertussis Vaccine in the Mouse

Pieroni, Robert E.; Levine, Leo

doi:10.1038/2111419a0

Cited by 19 publications

(12 citation statements)

References 9 publications

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“…Agents Chemother., abstr. G93, 1996) despite the The reduced response to polysaccharide was only seen when aP replaced wP in the combination, suggesting that either the loss of the general adjuvanticity of wP (19,21) or a potentially suppressive component of aP, such as FHA (16), may explain the observed phenomenon (20,23). The latter is unlikely as the reduction in polysaccharide response following primary immunization is seen only in the TT-conjugated serotypes, suggesting a degree of antigen specificity for this mechanism.…”

Section: Discussionmentioning

confidence: 62%

Reduction of Antibody Response to an 11-Valent Pneumococcal Vaccine Coadministered with a Vaccine Containing Acellular Pertussis Components

Dagan

Green

Maleckar³

et al. 2004

Infect Immun

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In pneumococcal conjugate vaccines (PCVs), polysaccharide antigens are often conjugated to protein carriers related to other common vaccines. It is therefore important to test PCV interaction with other pediatric vaccines when administered simultaneously. We assessed the immune response to an 11-valent PCV conjugated to diphtheria and tetanus carriers (PncD/T11), administered concomitantly, but in separate sites, with a combined vaccine containing epitopes related antigenically to the carriers: polyribosylribitol phosphate-tetanus toxoid (PRP-T), diphtheria toxoid (DT), and tetanus toxoid (TT). In addition, these combinations contained inactivated poliovirus vaccine (IPV) and either whole-cell pertussis (wP) or acellular pertussis (aP) components. After coadministration of PncD/T11 with the combined vaccine containing wP (DTwP/IPV/PRP-T), the responses to all polysaccharides in the PncD/T11 were satisfactory. In contrast, when coadministered with an aP-containing combination (DTaP/IPV/PRP-T), the response to all seven pneumococcal conjugates to TT was significantly reduced after primary and booster immunization. The pneumococcal conjugates to DT were not significantly reduced after the primary series, but were somewhat reduced after booster. It is likely that some suppression of the tetanus-mediated response occurred even when the PncD/T11 was coadministered with wP, but this suppression was masked by the adjuvant effect of wP. By replacing wP with aP, this adjuvant effect was removed, unmasking the suppression of the tetanus-mediated response. With the increasing use of multiple aP-containing vaccines in infancy, novel approaches to adjuvants and carrier protein technology are likely to be required.

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Section: Discussionmentioning

confidence: 62%

Reduction of Antibody Response to an 11-Valent Pneumococcal Vaccine Coadministered with a Vaccine Containing Acellular Pertussis Components

Dagan

Green

Maleckar³

et al. 2004

Infect Immun

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“…In animals treated with whole organisms, more injected lymphocytes reach periperal nodes and the spleen than in animals given BPCS, although in either case they remain unable to lodge in mesenteric nodes. It has been pointed out that whole pertussis organisms should be regarded as a mixture of antigens, endotoxins, and adjuvants (12,13). It was previously noted that locally injected pertussis organisms affect reticuloendothelial cells in draining lymph nodes, causing increased trapping of lymphocytes in lymphoid tissue, an effect opposite to the lymphocytosis after intravenous administration (5).…”

Section: Discussionmentioning

confidence: 99%

DISTRIBUTION OF LABELED LYMPH NODE CELLS IN MICE DURING THE LYMPHOCYTOSIS INDUCED BY BORDETELLA PERTUSSIS

Taub

Rosett

Adler

et al. 1972

The Journal of Experimental Medicine

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The mechanism by which Bordetella pertussis organisms and their products induce lymphocytosis in mice was analyzed in terms of the localization of syngeneic Cr-51-labeled lymph node cells. Labeled lymphoid cells incubated in vitro with the supernatant of B. pertussis cultures and then injected intravenously into normal recipients, or labeled cells injected into pertussis-treated recipients were unable to "home" to lymphoid organs but persisted for long periods in the blood. In animals "equipped" with a population of Cr-51-labeled lymphoid cells, administration of B. pertussis organisms or culture supernatant effected a shift of radioactivity from lymph nodes and spleen into the peripheral blood, coincident with the lymphocytosis. In in vitro experiments it was found that the active principle could bind to both erythrocytes and lymphocytes and could spontaneously elute from these cells onto labeled lymphocytes which were then unable to home efficiently. The data suggest that Bordetella pertussis-induced lymphocytosis involves a reversible attachment of the pertussis factor onto the surfaces of lymphocytes which prevents their recirculation to lymphoid organs. Recirculating lymphocytes are presumably affected as they emerge from lymphoid organs to enter the blood.

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“…For example, they might be employed in conjunction with leukophoresis as an alternative to thoracic duct drainage in lymphocyte depletion therapy. Alternatively, as suggested by their observed adjuvant activity in animals (4,6,12,17), they might be useful as adjuvants in tumor immunotherapy. With these possibilities in mind we are currently attempting to determine whether B pertussis vaccine administration in humans results in changes in lymphocyte distribution similar to those induced by natural infection.…”

Section: Discussionmentioning

confidence: 99%

Quantitation of Circulating T and B Lymphocytes in Children with Whooping Cough

1976

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ExtractThe numbers of circulating T and B lymphocytes in seven children with whooping cough due to Bordetella pertussis and eight control subjects were determined. All the children with whooping cough had an absolute lymphocytosis (mean 29,142/mm3 vs. 5,2251 mm3) and by surface marker criteria both T cells and B cells were increased (mean T cells, whooping cough 15,794/mm3 vs. 3,5161 mm3 controls; mean B cells, 13,393/mm3 whooping cough vs. 1,706/mm3 controls). However, the ratios of T cells to B cells in the whooping cough (1.4) and control group (1.9) did not differ significantly. This proportional increase in both T and B lymphocytes indicates that whatever mechanisms are responsible for lymphocytosis in B. pertussis infection affect both populations in a similar manner. SpeculationLymphocytosis in children with whooping cough results, primarily, from B. pertussis-induced blockage of T and B cell re-entry into lymph nodes from the blood. The profound effect of B. pertussis on lymphocyte recirculaticn patterns might be of value in future attempts at "immunologic engineering."B. pertussis infection of humans and experimental animals results in a striking increase in circulating lymphocytes (8,(12)(13)(14)(15)20). Animal studies suggest that this lymphocytosis represents an increase in both T and B cells (I, 6, 10) caused by a combination of two B. pertussis effects: blockage of lymphocyte re-entry into lymph nodes from the blood and increased lymphocyte release from lymphoid tissues into the circulation (1,8,(13)(14)(15)(16)18). Whether the characteristic lymphocytosis seen in children with whooping cough results from these same mechanisms is not known. In the hope of shedding some light on this question we have determined the proportions and absolute numbers of circulating T and B lymphocytes in seven children with whooping cough due to B. pertussis. The results of these experiments demonstrate that the lymphocytosis seen in children with whooping cough results from a proportional increase in both T and B lymphocytes. This finding supports the concept that the changes in lymphocyte distribution and circulation which have been documented in experimental animals infected with B. pertussis also occur in man and suggests that the main mechanism of B. pertussis-induced lymphocytosis is blockage of lymphocytes re-entry into lymph nodes rather than increased release from lymphoid organs. MATERIALS A N D METHODS PATIENTSThe patients' ages and diagnoses are shown in Table 1. The seven children with whooping cough ranged in age from 1-1 1 months. All were admitted to the Children's Hospital of Michigan between September 1974 and February 1975, all were in the paroxysmal stage of whooping cough when studied, and all had positive nasopharyngeal cultures for B. pertussis. Control subjects were eight afebrile, nonimmunosuppressed children from 1-24 months of age. Informed consent was obtained. QUANTITATION O F T A N D B LYMPHOCYTESWhite counts and differentials were performed on capillary blood obtained by finger stick. T...

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Adjuvant Principle of Pertussis Vaccine in the Mouse

Cited by 19 publications

References 9 publications

Reduction of Antibody Response to an 11-Valent Pneumococcal Vaccine Coadministered with a Vaccine Containing Acellular Pertussis Components

Reduction of Antibody Response to an 11-Valent Pneumococcal Vaccine Coadministered with a Vaccine Containing Acellular Pertussis Components

DISTRIBUTION OF LABELED LYMPH NODE CELLS IN MICE DURING THE LYMPHOCYTOSIS INDUCED BY BORDETELLA PERTUSSIS

Quantitation of Circulating T and B Lymphocytes in Children with Whooping Cough

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