Vaccine-Induced Human Antibody Responses to the Haemophilus influenzae b Polysaccharide in Severe Combined Immunodeficient Mice Engrafted with Human Leukocytes

Lucas, Alexander H.; Siff, Todd E.; Trujillo, Karen H; Kitamura, Marina

doi:10.1203/00006450-199207000-00026

Cited by 16 publications

(7 citation statements)

References 7 publications

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“…It therefore appeared that transfer of the cross‐reactive B cells from the donor was sufficient to generate T. muris specific IgG2 responses in hu‐PBL‐SCID mice in the absence of vaccination. A similar phenomenon has been noted for recall antigens in other hu‐PBL‐SCID mouse vaccination models (30,38). Overall, the hu‐PBL‐SCID mice vaccinated with T. muris antigens produced more consistent T. muris specific human IgG2 responses at higher levels than the mock‐vaccinated hu‐PBL‐SCID mice (with the exception of one mock‐vaccinated hu‐PBL‐SCID mouse discussed below) leading us to believe that vaccination was at least enhancing the donor’s cross‐reactive response.…”

Section: Discussionsupporting

confidence: 80%

Human Trichuris‐specific antibody responses in vaccinated hu‐PBL‐SCID mice

Taylor

Else

2002

Parasite Immunology

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Trichuris trichiura is a highly prevalent intestinal helminth of humans with a well-characterized animal model, Trichuris muris in the mouse. Relating the murine work back to the human infection has been difficult, however, as many of the questions addressed in the mouse cannot be asked in humans. The ability to reconstitute a mouse with a human immune system could help bridge this gap, allowing a human immune response to be studied under a controllable laboratory environment. In this study, we demonstrate that severe combined immunodeficient mice engrafted with naïve human peripheral blood lymphocytes are capable of mounting a Trichuris specific human antibody response after vaccination with T. muris antigens. The phenotype of the response depended on the vaccinating antigen with excretory/secretory antigens eliciting a human immunoglobulin IgG2 response, and whole worm homogenate stimulating IgG1 and IgG2 responses. Vaccination with homogenate also enhanced a human IgG response against a 66-kDa component of T. muris homogenate in a donor-dependent manner. This work shows the potential of using the humanized mouse model for studying the immune responses of humans living in T. trichiura endemic areas.

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Section: Discussionsupporting

confidence: 80%

Human Trichuris‐specific antibody responses in vaccinated hu‐PBL‐SCID mice

Taylor

Else

2002

Parasite Immunology

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“…Perhaps these cells secrete IgE for only a brief period because of a lack ofcontinuous stimulation in the SCID mice. Spontaneous human antibody production ceases soon after the PBL transfer into SCID mice if the cells are not first activated with antigen or if the mice are not subsequently immunized (6,7,10). Perhaps both IgE and IgG secretion that occurs after the engraftment of PBL into SCID mice is derived from relatively short-lived B cells.…”

Section: Resultsmentioning

confidence: 99%

“…C.B-17 scid/scid immunodeficient mice were bred and maintained at the Children's Hospital Oakland Research Institute ( 10) or the Animal Facilities of the University California at San Diego. Mice were housed in sterilized microbarrier units with sterilized bedding.…”

Section: Methodsmentioning

confidence: 99%

“…The predominant isotype of the human Ig in hu-PBL-SCID mice is IgG with smaller quantities of IgM and IgA (3,4). The IgG consists of both polyclonal IgG (4) and specific antibodies (5)(6)(7)(8)(9)(10) with the latter especially being the case if the donor has been recently immunized (2) or if the PBL are incubated with antigen in vitro followed by immunization of the mice (6). PBL from autoimmune patients also secrete specific antibodies in hu-PBL-SCID mice ( 1 1-13 ).…”

Section: Introductionmentioning

confidence: 99%

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Role of interleukin-4 in human immunoglobulin E formation in hu-PBL-SCID mice.

Spiegelberg¹,

Beck²,

Kocher³

et al. 1994

J. Clin. Invest.

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IntroductionWe studied the role of IL4 in human IgE formation in severe combined immunodeficient mice engrafted with peripheral blood mononuclear leukocytes (hu-PBL-SCID). PBL from four nonatopic donors produced only small (< 20 ng/ml) or undetectable amounts of IgE in SCID mice whereas engrafted PBL from seven atopic donors secreted IgE with IgE serum levels reaching a mean±SE of 184±37 ng/ml (n = 20). Serum IgE levels peaked 2-3 wk after PBL transfer and declined thereafter with a half-life of 1-2 wk. In contrast, IgG of all subclasses reached maximum serum levels 5-7 wk after PBL transfer and declined little thereafter. Injection of a neutralizing monoclonal antibody to the human IL4 receptor (IL4R) on day 0 inhibited completely the IgE formation and caused an approximate twofold reduction of IgG production of all subclasses. The anti-IL4 R antibody had no effect on IgE secretion when administered 4 wk after PBL engraftment. Incubation of PBL with IL4 before engraftment resulted in a 10-fold increase in IgE production and could be further enhanced by 100 fold if, in addition to preincubation with IL4, IL4 was injected daily for 5 d after PBL transfer. This treatment with IL4 also induced two-to threefold increase in IgG levels. IFN-'y had no effect on either IgE or IgG subclass production. In 50% of the mice, one or more IgG subclasses increased disproportionally 5 wk after PBL injection as a result of monoclonal IgG formation. These data demonstrate that PBL from atopic donors secrete IgE in SCID mice in an IL4-dependent manner, and that IgE production can be enhanced 10-to 100-fold with exogenous human IL4 in these mice. This mouse model is amenable for the in vivo study of immunomodulators on human IgE formation.(J. Clin. Invest. 1994.93:711-717.)

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“…However, a primary human immune response to T-dependent antigens has been difficult to obtain in SCID mice transplanted with human peripheral blood lymphocytes (SCID-PBL-hu mice) [2,4,5], whereas an antibody response to such antigens can be induced when the donors have been immunized with the antigen before transplantation [2,4,[6][7][8]. In contrast, a specific human anti-polysaccharide antibody response can be obtained after immunization of SCID-PBL-hu mice with polysaccharide antigens, which are T-independent antigens, when the mice are transplanted with cells from nonimmunized donors [9][10][11][12]. The antibodies induced are functional because SCID-PBL-hu mice are protected after challenge with virulent bacteria [9,11].…”

Section: Introductionmentioning

confidence: 99%

Human antibody response to a pneumococcal vaccine in SCID-PBL-hu mice and simultaneously vaccinated human cell donors

Aaberge¹,

Steinsvik²,

Groeng³

et al. 1996

Clinical and Experimental Immunology

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SUMMARYSevere combined immunodeficient (SCID) mice were transplanted intraperitoneally with human peripheral blood lymphocytes (PBL) from nine healthy human donors (SCID-PBL-hu mice). None of the donors had ever received pneumococcal vaccine. Ten days after transplantation, 62 out of 111 transplanted mice and six of the nine donors were vaccinated with a 23-valent pneumococcal polysaccharide vaccine. For each donor, human IgG was detected in 91 . 7-100% of the SCID-PBLhu mice, whereas specific human IgG antipneumococcal antibodies were demonstrated in 16 . 7-100% of the vaccinated SCID-PBL-hu mice. Most of the mice transplanted with cells from the same donor showed similar antibody response patterns in terms of kinetics and antibody levels. A significant antibody response was only obtained in mice that received cells from donors with relatively high antipneumococcal antibody levels at the time of transplantation, or donors that showed a substantial increase in antibody levels after vaccination. The immune response in the SCID-PBL-hu mice did not always reflect the ability of the respective donor to produce antipneumococcal antibodies. The donor dependency of the antipneumococcal antibody response has great practical importance for the use of the SCID-PBL-hu model. Donors should not be chosen randomly. By selecting donors whose cells have been found to result in successful engraftment, functional SCID-PBL-hu mice can be obtained for the study of human immune responses and function in an in vivo experimental model.

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Vaccine-Induced Human Antibody Responses to the Haemophilus influenzae b Polysaccharide in Severe Combined Immunodeficient Mice Engrafted with Human Leukocytes

Cited by 16 publications

References 7 publications

Human Trichuris‐specific antibody responses in vaccinated hu‐PBL‐SCID mice

Human Trichuris‐specific antibody responses in vaccinated hu‐PBL‐SCID mice

Role of interleukin-4 in human immunoglobulin E formation in hu-PBL-SCID mice.

Human antibody response to a pneumococcal vaccine in SCID-PBL-hu mice and simultaneously vaccinated human cell donors

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