Lipid vesicle-entrapped influenza A antigen modulates the influenza A-specific human antibody response in immune reconstituted SCID-human mice.
This study was designed to investigate the capacity of purified influenza antigen in the presence and absence of adjuvant to induce human antibody responses in human-PBL-SCID mice. Non-ionic surfactant vesicles (NISV) were used as adjuvant as they have been shown to promote the development of Th1 responses in mouse studies. Human peripheral blood lymphocyte-SCID mice were inoculated with either purified influenza antigen (A/Texas, H3N2) or influenza antigen entrapped in NISV. Both vaccinated groups produced significantly higher plasma levels of influenza-specific human IgG when individually compared with non-vaccinated controls. However, similar comparisons revealed that specific IgM levels were significantly higher only in the group challenged with purified antigen. Further analysis of IgG subclasses also demonstrated an adjuvant-dependent dichotomy in the responses of the vaccine groups when compared with non-vaccinated controls. Thus, only influenza-specific IgG1 antibodies (associated with Th1 responses in humans) were significantly increased above control levels using antigen with adjuvant, while both this subclass and antigen-specific IgG4 (Th2 associated) were significantly increased with antigen alone. These results illustrate the suitability of this model for use in human vaccination studies and demonstrates that influenza antigen applied with NISV selectively promotes only Th1 responses, unlike free antigen which also promotes Th2 responses in vivo.
Walker
W
W
Department of Immunology, University of Strathclyde, Glasgow, Scotland.
Brewer
J M
JM
Alexander
J
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis* / Q000145:classification; D000956:Antigens, Viral / Q000276:immunology*; D001782:Blood Donors; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D009980:Influenza A virus / Q000276:immunology*; D007274:Injections, Intraperitoneal; D008081:Liposomes / Q000276:immunology* / Q000494:pharmacology; D017710:Lymphocyte Transfusion; D051379:Mice; D016513:Mice, SCID; D014611:Vaccination; D014765:Viral Vaccines / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D007074:Immunoglobulin G; D008081:Liposomes; D014765:Viral Vaccines