Antibody

About: Antibody is a research topic. Over the lifetime, 113941 publications have been published within this topic receiving 4130181 citations. The topic is also known as: Ab & antibodies.

Human hepatitis B vaccine from recombinant yeast

Abstract: The worldwide importance of human hepatitis B virus infection and the toll it takes in chronic liver disease, cirrhosis and hepatocarcinoma, make it imperative that a vaccine be developed for worldwide application. Human hepatitis B vaccines are presently prepared using hepatitis B surface antigen (HBsAg) that is purified from the plasma of human carriers of hepatitis B virus infection. The preparation of hepatitis B vaccine from a human source is restricted by the available supply of infected human plasma and by the need to apply stringent processes that purify the antigen and render it free of infectious hepatitis B virus and other possible living agents that might be present in the plasma. Joint efforts between our laboratories and those of Drs W. Rutter and B. Hall led to the preparation of vectors carrying the DNA sequence for HBsAg and antigen expression in the yeast Saccharomyces cerevisiae. Here we describe the development of hepatitis B vaccine of yeast cell origin. HBsAg of subtype adw was produced in recombinant yeast cell culture, and the purified antigen in alum formulation stimulated production of antibody in mice, grivet monkeys and chimpanzees. Vaccinated chimpanzees were totally protected when challenged intravenously with either homologous or heterologous subtype adr and ayw virus of human serum source. This is the first example of a vaccine produced from recombinant cells which is effective against a human viral infection.

Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii.

Abstract: In vitro and in vivo studies were performed to assess the involvement of IL-12 in resistance to acute and chronic infection with an avirulent strain of Toxoplasma gondii. Our previous findings implicated macrophages as a major source of parasite-induced IL-12. This finding was confirmed by showing that peritoneal macrophages exposed to either live parasites or soluble tachyzoite Ags produce IL-12 protein. In mice, increased expression of IL-12 (p40) mRNA in both spleen and peritoneal cells was detected as early as 2 days postinfection. Treatment with neutralizing mAbs against IL-12 increased the susceptibility of C57BL/6, BALB/c, and severe combined immunodeficient (SCID) mice to acute infection, which resulted in 100% mortality within the first 15 days after parasite inoculation. In contrast, neutralization of endogenously produced IL-12 had no effect when given during chronic infection. In agreement with the survival data, treatment with anti-IL-12 resulted in decreased IFN-gamma and enhanced Th2 (IL-4 and IL-10) cytokine synthesis by splenocytes when given during acute, but not chronic, toxoplasmosis. Sorting experiments on spleen cells from acutely infected mice indicated that both CD4+ lymphocytes and NK1.1+/CD3- cells contribute to the early IFN-gamma response. In contrast, CD4+ cells were found to be the major source of the cytokine during chronic disease. Together, these results suggest that the stimulation of macrophage-derived IL-12 plays a major role in both the induction of resistance and Th1 cell subset selection in acute T. gondii infection, but may not be required to maintain established immunity.

Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens.

Abstract: The long-standing hypothesis that tolerance to self antigens is mediated by either elimination or functional inactivation (anergy) or self-reactive lymphocytes is now accepted, but little is known about the factors responsible for initiating one process rather than the other. In the B-cell lineage, tolerant self-reactive cells persist in the peripheral lymphoid organs of transgenic mice expressing lysozyme and anti-lysozyme immunoglobulin genes, but are eliminated in similar transgenic mice expressing anti-major histocompatibility complex immunoglobulin genes. By modifying the structure of the lysozyme transgene and the isotype of the anti-lysozyme immunoglobulin genes, we demonstrate here that induction of anergy or deletion is not due to differences in antibody affinity or isotype, but to recognition of monomeric or oligomeric soluble antigen versus highly multivalent membrane-bound antigen. Our findings indicate that the degree of receptor crosslinking can have qualitatively distinct signalling consequences for lymphocyte development.

γ Interferon, CD8 + T cells and antibodies required for immunity to malaria sporozoites

Abstract: This study was designed to test the hypothesis that T-cell effector mechanisms are required for protective immunity to malaria sporozoites. Administration of neutralizing monoclonal antibodies against gamma interferon (gamma IFN) to immune hosts, reversed sterile immunity to sporozoite challenge, by allowing the growth of exoerythrocytic forms (EEF) and thus the development of parasitaemia. Immune animals also developed infections when depleted in vivo of their suppressor/cytotoxic T cells expressing the CD8 antigen (CD8+) but not when depleted of helper T cells expressing CD4 antigen (CD4+), before sporozoite challenge. Passive transfer of immune immunoglobin alone, or adoptive transfer of immune T cells alone, conferred partial protection to naive recipients. Transfer of both immune components resulted in significantly greater protection. This transferred immunity was reversed by the in vivo neutralization of gamma IFN. Thus, sterile immunity to sporozoite challenge requires the neutralization of sporozoites by antibodies and the inhibition of EEF development by gamma IFN with the participation of CD8+ cells.