摘要:

ABSTRACTGenetic immunization, the latest addition to the field of vaccinology, has shown, in a number of animal models, to be an efficacious approach to induce protective immunity to infectious diseases. The advantages of DNA vaccines are their ease of construction, the low expanse of mass production, their high temperature stability, and their ability to induce a full spectrum of exceptionally long-lasting immune responses including cytolytic T cells. Their potential disadvantages are putative safety issues such as integration into the host cell genome. The slow development of the immune response to genetic immunization will make these vaccines unsuitable for treatment of some infectious diseases such as postexposure vaccination to rabies virus, where a rapid immune response is warranted. Although only time will tell if genetic immunization provides a viable alternative for human immunization, in the meantime this approach provides immunologists with a powerful tool to gain further insight in the mechanisms that drive primary immune responses.

ISSN:0882-8245    

DOI:10.1089/vim.1996.9.1

年代:1996

数据来源: MAL

摘要:

ABSTRACTFor the development of veterinary subunit vaccines, modifications to the antigen may be needed to make the production of these vaccines cost effective. To investigate the effect of antigen modifications on immune response, we used glycoprotein D, one of the major glycoproteins of bovine herpesvirus-1 (BHV-1), as a model antigen. We developed a mouse model to assess the immune response elicited by immunization with either a recombinant truncated (tgD) or the authentic full-length (gD) form of BHV-1 gD in VSA3, a novel water-in-oil adjuvant. Both forms of BHV-1 gD antigen induced good levels of cell-mediated immunity, as evaluated by antigen-specific proliferative response and cytokine (IFN-γ and IL-4) production. Following primary immunization, the humoral immune response induced by gD was superior to that elicited by vaccination with tgD. However, after a secondary immunization, a strong and similar antibody response to BHV-1 gD was induced by both forms of the antigen. The difference in immunogenicity between gD and tgD after primary immunization was not due to the loss of immunogenic epitopes in the truncated antigen or the ability to associate with the adjuvant VSA3. Our results indicate that both gD and tgD are capable of efficiently inducing a cell-mediated immune response, and although recombinant tgD is less efficient in inducing a primary humoral immune response when compared to the full-length gD, tgD effectively primed for a secondary antibody response

ISSN:0882-8245    

DOI:10.1089/vim.1996.9.11

年代:1996

数据来源: MAL

ISSN:0882-8245    

DOI:10.1089/vim.1996.9.23

年代:1996

数据来源: MAL

摘要:

ABSTRACTHuman peripheral blood mononuclear cells (PBMC) and their subpopulations obtained from healthy donors were used to study improvement of MHC-unrestricted cytotoxic reactions against cells infected with human cytomegalovirus (HCMV) at different multiplicities of infection. Natural killer (NK) and lymphokine-activated killer (LAK) cytotoxicity against HCMV-infected cells was greatly enhanced in the presence of rhamnogalacturonan (500 ng/ml). The increase of the multiplicity of infection from MOI 0.1 to 1.0 had only a slight effect on cytotoxicity enhancement by rhamnogalacturonan. The chemical specificity of interaction of rhamnogalacturonan with effector cells and virus-infected cells was found to be analogous to the interaction with tumor cells, i.e., both types of target cells must express a receptor for rhamnogalacturonan since rhamnogalacturonan-mediated enhancement of NK and LAK cytotoxicity against HCMV-infected cells was similarly inhibited by preincubation of CD56+effector cells with 60% deacetylated d-mannose pentaacetate.

ISSN:0882-8245    

DOI:10.1089/vim.1996.9.27

年代:1996

数据来源: MAL

摘要:

ABSTRACTWe previously generated rabbit polyclonal antiidiotypic antibody (anti-Id) to a murine monoclonal antibody (M1875) specific for the bluetongue virus core protein VP7, and demonstrated that this anti-Id (designated RAb2-A) had the characteristics of an internal image anti-Id (Ab2β). In this communication, RAb2-A was used to induce immune responses in sheep and the responses were compared to immunization with VP7. The immune sera were tested for the presence of anti-VP7 antibodies and the expression of the Id of M1875. Animals immunized with RAb2-A were able to produce M1875-like antibody responses, i.e., they recognized the same or a similar epitope as M1875 and possessed the M1875 Id, without subsequent exposure to the original antigen. This was demonstrated by showing that antibodies induced by RAb2-A (i) reacted specifically with the immunizing anti-Id, (ii) were capable of binding VP7, (iii) inhibited M1875 from binding to VP7, and (iv) inhibited M1875 from binding to RAb2-A. Animals immunized with purified VP7 produced antibodies that possessed the epitope and idiotope specificity of M1875. No antibody responses to VP7 were detected in control animals immunized with either rabbit anti-Id to the pseudorabies virus glycoprotein gIII or BHK-21 cell proteins. We conclude that rabbit anti-Id RAb2-A serologically mimics an M1875-defined VP7 epitope sufficiently to function as a surrogate antigen for inducing anti-bluetongue virus VP7 responses

ISSN:0882-8245    

DOI:10.1089/vim.1996.9.35

年代:1996

数据来源: MAL

摘要:

ABSTRACTEpstein–Barr virus (EBV) is the etiological agent for acute infectious mononucleosis (AIM). It is also associated with certain malignant disorders in individuals with immunodeficiencies such as B cell lymphoproliferative disorder (BLPD). Our previous study with BLPD patients had demonstrated significantly higher serum IL-4 and IgE levels and significantly decreased IFN-α levels. These observations were consistent with the model of regulation of B cell growth by T cell-derived cytokines, in which IL-4 promotes B cell growth and switch to IgE synthesis whereas IFN-α and IFN-γ inhibit these IL-4-mediated effects. Since AIM is also EBV associated, this study was designed to examine IL-4, IFN-α, IFN-γ, IgE, and soluble CD23 (sCD23) serum levels in AIM patients. In this study we report for the first time that in contrast to BLPD patients, AIM patients did not exhibit increased levels of IL-4 and IgE; however AIM patients do exhibit decreased IFN-α levels and, additionally, also exhibit significantly higher sCD23 levels. This could result in B cell activation and have implications for the survival of the virus in

ISSN:0882-8245    

DOI:10.1089/vim.1996.9.45

年代:1996

数据来源: MAL

摘要:

ABSTRACTInfection of porcine alveolar macrophages by the porcine reproductive and respiratory syndrome virus (PRRSV) was significantly enhancedin vitroby antibody raised against the PRRSV isolate ISU-P (p<0.01). Increased yields and infection rates were highly correlated (r= 0.95) and the ratio of yield to infection rate was greater than 1.4, suggesting that more than one mechanism was responsible for enhanced infection. Antibody-dependent enhancement (ADE) of infection was also demonstrated in vivo using a completely randomized block design (n= 16). The mean level and duration of viremia were greater (p<0.05) in pigs injected with subneutralizing amounts of PRRSV-specific IgG prior to virus challenge than in control pigs injected with normal IgG. In contrast, virus replication was significantly (p<0.01) inhibited in pigs with neutralizing antibody titers of 4 log2. The period of time that subneutralizing levels of antibody can persist and contribute to ADE of PRRSV infection was estimated in 4 pigs injected with PRRSV-specific IgG to yield an initial neutralizing antibody titer of 3.8 log2. Neutralizing activity declined to undetectable levels by day 37 postinjection (PI). ADE activity was first detected in undiluted sera on day 20 PI and persisted through day 62 PI. Western immunoblot analysis of sera collected between days 37 and 62 PI detected antibodies specific for the 15-kDa nucleocapsid and 26-kDa glycosylated envelope proteins. These results strongly suggest that ADE has the potential to contribute to the pathogenesis of PRRSV infection and is mediated by antibody specific for the 26-kDa envelope protein.

ISSN:0882-8245    

DOI:10.1089/vim.1996.9.51

年代:1996

数据来源: MAL