PMID- 26410104 OWN - NLM STAT- MEDLINE DCOM- 20160427 LR - 20151215 IS - 1872-7905 (Electronic) IS - 0022-1759 (Linking) VI - 427 DP - 2015 Dec TI - Human immune system mice immunized with Plasmodium falciparum circumsporozoite protein induce protective human humoral immunity against malaria. PG - 42-50 LID - S0022-1759(15)30047-8 [pii] LID - 10.1016/j.jim.2015.09.005 [doi] AB - In this study, we developed human immune system (HIS) mice that possess functional human CD4+ T cells and B cells, named HIS-CD4/B mice. HIS-CD4/B mice were generated by first introducing HLA class II genes, including DR1 and DR4, along with genes encoding various human cytokines and human B cell activation factor (BAFF) to NSG mice by adeno-associated virus serotype 9 (AAV9) vectors, followed by engrafting human hematopoietic stem cells (HSCs). HIS-CD4/B mice, in which the reconstitution of human CD4+ T and B cells resembles to that of humans, produced a significant level of human IgG against Plasmodium falciparum circumsporozoite (PfCS) protein upon immunization. CD4+ T cells in HIS-CD4/B mice, which possess central and effector memory phenotypes like those in humans, are functional, since PfCS protein-specific human CD4+ T cells secreting IFN-gamma and IL-2 were detected in immunized HIS-CD4/B mice. Lastly, PfCS protein-immunized HIS-CD4/B mice were protected from in vivo challenge with transgenic P. berghei sporozoites expressing the PfCS protein. The immune sera collected from protected HIS-CD4/B mice reacted against transgenic P. berghei sporozoites expressing the PfCS protein and also inhibited the parasite invasion into hepatocytes in vitro. Taken together, these studies show that our HIS-CD4/B mice could mount protective human anti-malaria immunity, consisting of human IgG and human CD4+ T cell responses both specific for a human malaria antigen. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Huang, Jing AU - Huang J AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA. FAU - Li, Xiangming AU - Li X AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA. FAU - Coelho-dos-Reis, Jordana G A AU - Coelho-dos-Reis JG AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA. FAU - Zhang, Min AU - Zhang M AD - Department of Pathology, New York University School of Medicine, New York, NY, USA. FAU - Mitchell, Robert AU - Mitchell R AD - Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY, USA. FAU - Nogueira, Raquel Tayar AU - Nogueira RT AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA. FAU - Tsao, Tiffany AU - Tsao T AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA. FAU - Noe, Amy R AU - Noe AR AD - Leidos, San Diego, CA, USA. FAU - Ayala, Ramses AU - Ayala R AD - Leidos, Frederick, MD, USA. FAU - Sahi, Vincent AU - Sahi V AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA. FAU - Gutierrez, Gabriel M AU - Gutierrez GM AD - Leidos, Frederick, MD, USA. FAU - Nussenzweig, Victor AU - Nussenzweig V AD - Department of Pathology, New York University School of Medicine, New York, NY, USA. FAU - Wilson, James M AU - Wilson JM AD - Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Nardin, Elizabeth H AU - Nardin EH AD - Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY, USA. FAU - Nussenzweig, Ruth S AU - Nussenzweig RS AD - Division of Parasitology, Department of Microbiology, New York University School of Medicine, New York, NY, USA. FAU - Tsuji, Moriya AU - Tsuji M AD - Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, New York, NY, USA. Electronic address: mtsuji@adarc.org. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150926 PL - Netherlands TA - J Immunol Methods JT - Journal of immunological methods JID - 1305440 RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Malaria Vaccines) RN - 0 (Protozoan Proteins) RN - 0 (circumsporozoite protein, Protozoan) SB - IM MH - Animals MH - *Disease Models, Animal MH - Enzyme-Linked Immunosorbent Assay MH - Heterografts MH - Histocompatibility Antigens Class II MH - Humans MH - Immunity, Humoral/*immunology MH - Malaria Vaccines MH - Malaria, Falciparum/*immunology MH - Mice MH - Mice, Transgenic/*immunology MH - Protozoan Proteins/immunology OTO - NOTNLM OT - HLA class II molecule OT - Human IgG OT - Human immune system mice OT - P. falciparum circumsporozoite protein OT - Protective anti-malaria immunity EDAT- 2015/09/28 06:00 MHDA- 2016/04/28 06:00 CRDT- 2015/09/28 06:00 PHST- 2015/05/15 00:00 [received] PHST- 2015/08/17 00:00 [revised] PHST- 2015/09/23 00:00 [accepted] PHST- 2015/09/28 06:00 [entrez] PHST- 2015/09/28 06:00 [pubmed] PHST- 2016/04/28 06:00 [medline] AID - S0022-1759(15)30047-8 [pii] AID - 10.1016/j.jim.2015.09.005 [doi] PST - ppublish SO - J Immunol Methods. 2015 Dec;427:42-50. doi: 10.1016/j.jim.2015.09.005. Epub 2015 Sep 26.