Experiments designed to determine the mechanism of the adjuvant activity of Gram-negative organisms upon antibody production

Farthing, J. R.; Holt, L. B.

doi:10.1017/s0022172400020544

Cited by 15 publications

(16 citation statements)

References 11 publications

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“…Several workers have shown that B. pertussis enhances the primary immune response only when given either together or within 24 hr after the antigen (4,18,22,26). B. pertussis given 24 hr before antigen was unable to enhance the primary immune response in mice (18), rats (26), and guinea pigs (4). Similar observations have been made with bacterial endotoxins (22).…”

mentioning

confidence: 63%

“…Killed Bordetella pertussis cells act as adjuvant to various antigens in man and animals (4,8,14,22,28). This effect is evidently due to an acceleration and prolongation of multiplication of the antibody-producing cells (8, 11).…”

mentioning

confidence: 99%

“…One of the most important aspects regarding the mode of action of immunological adjuvants is the time relationship between injection of antigen and of adjuvant. Several workers have shown that B. pertussis enhances the primary immune response only when given either together or within 24 hr after the antigen (4,18,22,26). B. pertussis given 24 hr before antigen was unable to enhance the primary immune response in mice (18), rats (26), and guinea pigs (4).…”

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confidence: 99%

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Time Relationships Between Injection of Antigen and Adjuvant I. Adjuvancy of Bordetella pertussis Given at Various Times Before the Primary Antigenic Stimulus

1970

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The adjuvant activity of Bordetella pertussis was investigated, both at the cellular and humoral levels, when the bacterial adjuvant was administered at various times before the primary antigenic stimulus of both 8 X 106 and 4 X 108 sheep erythrocytes. In all experiments, both adjuvant and erythrocyte antigen were given intraperitoneally. Adjuvant activity was measured on the basis of the primary immune response and on the degree of priming for the secondary immune reaction. A maximal effect on the primary immune response was found in mice which had received B. pertussis vaccine simultaneously with the erythrocyte antigen. A significant degree of adjuvancy was also demonstrable when B. pertussis vaccine was administered within a period of 48 hr before antigen. Adjuvant effectiveness was less as the time interval between the injection of antigen and adjuvant increased. The process of priming for the secondary response, however, was found to be equally affected when the adjuvant was given either simultaneously with the antigen or 12, 24, and 48 hr before sheep erythrocytes. On the basis of these and previous findings, it is suggested that adjuvancy of B. pertussis is caused chiefly by additional recruitment of responding cells. It is also suggested that memory-cell production may develop concurrently with, but independently of, the cellular proliferative events which lead to antibody formation during the primary immune response. Central Institute for Laboratory Animals in Hannover, Germany. Antigen. Primary immunizations were performed with either 8 X 106 or 4 X 108 sheep erythrocytes(SE), each dose suspended in 0.2 ml of phosphate-buffered saline (PBS), pH 7.2. Secondary immunization con-590

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confidence: 63%

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confidence: 99%

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confidence: 99%

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Time Relationships Between Injection of Antigen and Adjuvant I. Adjuvancy of Bordetella pertussis Given at Various Times Before the Primary Antigenic Stimulus

1970

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“…Gram-negative organisms have a pronounced stimulatory effect on antibody production, and this adjuvant effect appears to be due to their endotoxin content (for a review, see Neter, 1969). Specifically, isolated Bordetella pertussis LPS has been shown to act as an adjuvant by Farthing & Holt (1962) and by Nakase, Tateisi, Sekiya & Kasuga (1970). The ability of strain I34 to increase the primary response of mice to human group A erythrocytes was therefore examined; this strain was found to be as good an adjuvant as any of the strains tested.…”

Section: J P a C K E R S And J M D O L B Y 380mentioning

confidence: 99%

The Antigen of Bordetella pertussis that Induces Bactericidal Antibody and its Relationship to Protection of Mice

Ackers

Dolby

1972

Journal of General Microbiology

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S U M M A R YThe ability to protect mice against intracerebral infection and to elicit, after one dose, complement-mediated bactericidal antibody capable of killing a mousevirulent phase I strain in vitro, was tested in seven cultures of Bordetellapertussis: three typical phase I strains; two strains grown in the presence of 0.5 mg nicotinic acid/ml ; one phase IV strain ; and the atypical strain 134. The typical strains showed both activities; the nicotinic acid-grown and phase IV strains elicited high antibody titres, but did not confer protection, whereas strain 134 protected, but did not elicit bactericidal antibody.Pyrogenic material extracted from dried organisms by hot phenol and water (lipopolysaccharide) was not antigenic in mice; however, with all strains, except 134, multiple doses of this material coupled to stromata or Escherichiu coli conjugated protein elicited bactericidal and precipitating antisera in mice, although the mice were not protected.Strain 134 contained approximately one quarter of the normal amount of endotoxin, as assayed in actinomycin D-sensitized mice, but was as effective as normal strains as an adjuvant for haemolysin production.

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“…DISCUSSION Among the various biologically active substances from B. pertussis, pertussigen, DNT, LPS, K-agglutinogen, and FHA have been obtained in a purified form by various workers (1-3, 6, 16, 21, 27, 33, 36-38, 40, 41, 47, 55). Of these substances, pertussigen and LPS increase the production of antibodies to protein antigens given with them (4,9,10,22,23,25,30,32,42,49), and pertussigen is the most effective adjuvant for the stimulation of IgGl and IgE antibodies (34). Other immunoglobulins are also increased by pertussis vaccine (7,11,12,32,48), but no studies have been reported employing purified pertussigen to determine its effect on the levels of antibodies of other immunoglobulin classes.…”

Section: Effect Of Individual Components Given 5 Days Before On the Amentioning

confidence: 99%

Effects of Bordetella pertusiss Components on IgE and IgG1 Responses

Sekiya

1983

Microbiology and Immunology

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The effect of dermonecrotic toxin (DNT), fimbrial hemagglutinin (FHA), K-agglutinogen, lipopolysaccharide (LPS), and pertussigen from Bordetella pertussis on the production of IgE and IgGI antibodies to hen egg albumin (Ea) was investigated in C57BL/6 mice. The IgE antibody contents were determined by passive cutaneous anaphylaxis (PCA) in the skin of Lewis rats, while the IgG I antibody contents were determined by PCA reactions on the skin of mice using sera that had been heated for 3 hr at 56 C to destroy the IgE antibodies. Among the B. pertussis components tested, pertussigen was the most effective adjuvant for increasing the IgE and IgG I antibodies to Ea. LPS also moderately increased both types of antibodies, and FHA slightly increased the IgGI titers. When LPS was given 5 days before Ea, it suppressed both IgE and IgGI titers while FHA had only slight adjuvant action on both type of antibodies.When each of the components was tested for its ability to modify the adjuvant action of pertussigen, it was found that only DNT interfered significantly with the adjuvanticity ofpertussigen when given on the day of immunization with Ea. When the components were given 5 days before Ea, DNT produced significant suppression of only the IgGI response. LPS, FHA, and K-agglutinogen did not significantly affect the adjuvant action of pertussigen, B. pertussis cells excert an adjuvant effect on the production of antibodies in man and animals (32). This ability is shared by the lipopolysaccharides (LPS) of most gram-negative bacteria (26), but the adjuvant action of B. pertussis is due not entirely to LPS, but also to a protein called pertussigen by Munoz and coworkers (32) which has been referred to as a leukocytosis-promoting factor (LPF), leukocytosis-promoting factor-hemagglutinin (LPF-HA), histamine-sensitizing factor (HSF), and islet-activating protein (lAP) (6,34,45,51). Pertussigen has the unique property of enhancing the IgE class of immunoglobulins, an effect first observed by Mota (28) employing whole-cell pertussis vaccine. Many investigators have since confirmed the adjuvant action of pertussis vaccine and pertussigen (32). Munoz et al (34) found that as little as 0.1 ng of highly purified crystalline pertussigen increased production of IgE and IgG 1 antibodies to hen egg albumin (Ea).

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Experiments designed to determine the mechanism of the adjuvant activity of Gram-negative organisms upon antibody production

Cited by 15 publications

References 11 publications

Time Relationships Between Injection of Antigen and Adjuvant I. Adjuvancy of Bordetella pertussis Given at Various Times Before the Primary Antigenic Stimulus

Time Relationships Between Injection of Antigen and Adjuvant I. Adjuvancy of Bordetella pertussis Given at Various Times Before the Primary Antigenic Stimulus

The Antigen of Bordetella pertussis that Induces Bactericidal Antibody and its Relationship to Protection of Mice

Effects of Bordetella pertusiss Components on IgE and IgG1 Responses

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