The Immune Response in Guinea Pigs Injected with Heterologous and Altered Homologous Thyroglobulin

1967 ◽  
Vol 31 (6) ◽  
pp. 559-567
Author(s):  
H.L. Spiegelberg ◽  
W.O. Weigle
Keyword(s):  
1999 ◽  
Vol 37 (2) ◽  
pp. 123-129 ◽  
Author(s):  
B. R. Mignon ◽  
T. Leclipteux ◽  
CH. Focant ◽  
A. J. Nikkels ◽  
G. E. PIErard ◽  
...  

1971 ◽  
Vol 134 (2) ◽  
pp. 517-531 ◽  
Author(s):  
Joseph M. Davie ◽  
Alan S. Rosenthal ◽  
William E. Paul

Guinea pigs immunized with 2,4-dinitrophenyl-guinea pig albumin (DNP-GPA) possess lymphocytes which specifically bind sufficient DNP-GPA-125I to their surface to be detected by radioautography. These lymphocytes are present in the draining lymph nodes in a frequency of ∼50/1000 lymphocytes in animals immunized 2–4 wk earlier with DNP-GPA in complete Freund's adjuvant. Nonimmunized animals have ∼0.4 DNP-GPA antigen-binding cells (ABC) per 1000 lymphocytes. An increase in the frequency of DNP-GPA ABC in peripheral blood is detectable by 5 days after immunization, which is before the time that serum anti-DNP antibody is measurable. The receptors of these ABC are hapten specific in that free ϵ-DNP-L-lysine, at low concentration, inhibits the binding of DNP-GPA-125I; DNP bovine serum alumbin (DNP-BSA) is equivalent to DNP-GPA in the inhibition of binding of DNP-GPA-125I to ABC; and both DNP-GPA agarose beads and DNP-BSA agarose beads specifically adsorb DNP-GPA-125I ABC. Anti-immunoglobulin antisera, particularly anti-γ2 sera, inhibit the binding of DNP-GPA-125I to these cells implying that the receptors are immunoglobulin, primarily of the γ2 heavy chain class. DNP-GPA-125I ABC appear to represent precursors of antibody-secreting cells and have specificity characteristics which are very different from cells, of similarly immunized guinea pigs, which mediate a cellular immune response to DNP-GPA.


mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
pp. e00583-17 ◽  
Author(s):  
K. Ross Turbyfill ◽  
Kristen A. Clarkson ◽  
Anthony R. Vortherms ◽  
Edwin V. Oaks ◽  
Robert W. Kaminski

ABSTRACTThe native Invaplex (InvaplexNAT) vaccine and adjuvant is an ion exchange-purified product derived from the water extract of virulentShigellaspecies. The key component of InvaplexNATis a high-molecular-mass complex (HMMC) consisting of theShigellalipopolysaccharide (LPS) and the invasin proteins IpaB and IpaC. To improve product purity and immunogenicity, artificial Invaplex (InvaplexAR) was developed using recombinant IpaB and IpaC proteins and purifiedShigellaLPS to assemble an HMMC consisting of all three components. Characterization of InvaplexARby various methods demonstrated similar characteristics as the previously reported HMMC in InvaplexNAT. The well-defined InvaplexARvaccine consistently contained greater quantities of IpaB, IpaC, and LPS than InvaplexNAT. InvaplexARand InvaplexNATimmunogenicities were compared in mouse and guinea pig dose escalation studies. In both models, immunization induced antibody responses specific for InvaplexNATand LPS while InvaplexARinduced markedly higher anti-IpaB and -IpaC serum IgG and IgA endpoint titers. In the murine model, homologous protection was achieved with 10-fold less InvaplexARthan InvaplexNATand mice receiving InvaplexARlost significantly less weight than mice receiving the same amount of InvaplexNAT. Moreover, mice immunized with InvaplexARwere protected from challenge with both homologous and heterologousShigellaserotypes. Guinea pigs receiving approximately 5-fold less InvaplexARcompared to cohorts immunized with InvaplexNATwere protected from ocular challenge. Furthermore, adjuvanticity previously attributed to InvaplexNATwas retained with InvaplexAR. The second-generationShigellaInvaplex vaccine, InvaplexAR, offers significant advantages over InvaplexNATin reproducibility, flexible yet defined composition, immunogenicity, and protective efficacy.IMPORTANCEShigellaspecies are bacteria that cause severe diarrheal disease worldwide, primarily in young children. Treatment of shigellosis includes oral fluids and antibiotics, but the high burden of disease, increasing prevalence of antibiotic resistance, and long-term health consequences clearly warrant the development of an effective vaccine. OneShigellavaccine under development is termed the invasin complex or Invaplex and is designed to drive an immune response to specific antigens of the bacteria in an effort to protect an individual from infection. The work presented here describes the production and evaluation of a new generation of Invaplex. The improved vaccine stimulates the production of antibodies in immunized mice and guinea pigs and protects these animals fromShigellainfection. The next step in the product’s development will be to test the safety and immune response induced in humans immunized with Invaplex.


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