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

Abstract

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.

An Exploratory Trial of Cyclooxygenase Type 2 Inhibitor in HIV-1 Infection: Downregulated Immune Activation and Improved T Cell-Dependent Vaccine Responses

“…In a substudy, we tested the response to one injection of each of two standard vaccines at study week 6; 23 volunteers among the study participants gave their separate informed consent and received the T cell-dependent tetanus toxoid (TT) vaccine (Tetavax; Sanofi Pasteur MSD), and 21 also received the T cellindependent pneumococcal polysaccharide vaccine (PP) (Pneumovax 23; Sanofi Pasteur MSD). IgG antibodies to the tetanus toxoid (50) and 23-valent pneumococcal polysaccharide vaccines were both measured with ELISA in the same assay poststudy, using thawed sera, the latter after C polysaccharide adsorption of sera (1). Vaccine responses to TT and PP vaccines were assessed as differences in specific IgG levels between study week 12 and the time of vaccination (week 6).…”

Induction of Protective Immune Responses against R5 Human Immunodeficiency Virus Type 1 (HIV-1) Infection in hu-PBL-SCID Mice by Intrasplenic Immunization with HIV-1-Pulsed Dendritic Cells: Possible Involvement of a Novel Factor of Human CD4+T-Cell Origin

“…It has been shown that the human T cells transplanted into SCID mice are activated (26) and proliferate in response to nominal antigens presented by antigen-presenting cells (APC) of murine origin (34). Thus, experiments have been conducted to induce and study human immune responses in hu-PBL-SCID mice (1,3,7,17). There are, however, two major limitations to the development of strong human immune responses in these hu-PBL-SCID mice.…”

Are polysaccharide antibody responses independent: the T cell enigma?

“…CD22 is linked by its cytoplasmic tail to the tyrosine phosphatase PTP-1C, and cross-linking CD22 primes B cells for subsequent activation by cross-linking surface immunoglobulin. It has been suggested that marginal zone macrophages might physiologically prime marginal zone B cells by engaging CD22 [14], and this would fit well with the activated status of Given that responses to TI-2 antigens require complex protein interactions between B cells and accessory cells, and in some cases at least T cells, how accurately do the experiments reported in this issue [15], where human peripheral blood lymphocytes are used to reconstitute immunodeficient SCID mice, represent the normal physiological response to TI-2 antigens? They may prove to be misleading, as too many important interactions between murine and human cells do not work.…”