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Context: Children and adolescents appear to play an important role in the transmission of influenza. Selectively vaccinating youngsters against influenza may interrupt virus transmission and protect those not immunized.Objective: To assess whether vaccinating children and adolescents with inactivated influenza vaccine could prevent influenza in other community members.Design, Setting, and Participants: A cluster randomized trial involving 947 Canadian children and adolescents aged 36 months to 15 years who received study vaccine and 2326 community members who did not receive the study vaccine in 49 Hutterite colonies in Alberta, Saskatchewan, and Manitoba. Follow-up began December 28, 2008, and ended June 23, 2009.Intervention: Children were randomly assigned according to community and in a blinded manner to receive standard dosing of either inactivated trivalent influenza vaccine or hepatitis A vaccine, which was used as a control.Main Outcome Measures: Confirmed influenza A and B infection using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay and by measuring serum hemagglutination inhibition titers.Results: The mean rate of study vaccine coverage among eligible participants was 83% (range, 53%-100%) for the influenza vaccine colonies and 79% (range, 50%-100%) for the hepatitis A vaccine colonies. Among nonrecipients, 39 of 1271 (3.1%) in the influenza vaccine colonies and 80 of 1055 (7.6%) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR, for a protective effectiveness of 61% (95% confidence interval [CI], 8%-83%; P = .03). Among all study participants (those who were and those who were not vaccinated), 80 of 1773 (4.5%) in the influenza vaccine colonies and 159 of 1500 (10.6%) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR for an overall protective effectiveness of 59% (95% CI, 5%-82%; P = .04). No serious vaccine adverse events were observed.Conclusion: Immunizing children and adolescents with inactivated influenza vaccine significantly protected unimmunized residents of rural communities against influenza.Trial Registration: clinicaltrials.gov Identifier: NCT00877396. [ABSTRACT FROM AUTHOR]

The article discusses the concepts and challenges of vaccination and covers information on the use of nucleic acids as vaccines, which is referred to as DNA vaccination. The observation that if an individual recovered from the specific infection, they were protected from subsequent infection, gave rise to the concept of vaccination. From a mechanistic viewpoint, the use of pure plasmid DNA offers many advantages over other vaccine delivery vehicles.

We have previously reported on the use of a tobacco mosaic virus (TMV) vector TMV-30B to express foreign viral antigens for use as experimental immunogens. Here we describe the development of an improved TMV-30B vector that adds a sequence of 7 histidine residues to the C-terminus of recombinant proteins expressed in the vector. We used this TMV-30B-HISc vector to express the VP8* fragment of the VP4 protein from bovine rotavirus (BRV) strain C-486 in plants. Recombinant VP8* protein was purified fromN. benthamianaleaves at 7 days post-inoculation by immobilized metal affinity chromatography. The plant-produced VP8* was initially detected using anti-His tag mAb and its antigenic nature was confirmed using both monoclonal and polyclonal specific antisera directed against BRV. Adult female mice, inoculated by the intraperinoteal route with an immunogen containing 4?µg of recombinant VP8*, developed a specific and sustained response to the native VP8* from the homologous BRV. Eighty five percent of suckling mice from immunized dams that were challenged with the homologous virus at the fifth day of age were protected from virus as compared to 35% of the pups from mothers immunized with a control protein. These results demonstrate that the plant-produced VP8* was able to induce passive protection in the new born through the immunization of dams. This suggests that the technology presented here provides a simple method for using plants as an inexpensive alternative source for production of recombinant anti-rotavirus antigens. [ABSTRACT FROM AUTHOR]

Antibody-mediated complement lysis of Vero cells and canine macrophages infected with canine distemper virus (CDV) was demonstrated in an in vitro 51Cr release assay. This cytolytic activity was found to be highly efficient and was optimal under conditions which favoured the capping of redistribution of surface viral antigens. A prozone was observed in the presence of high antibody concentration and could not be eliminated by repeated washings. By tagging antibody-coated target cells with 125I-labelled staphylococcus protein A. it was found that the extent of protein A binding was parallel to the degree of cytotoxicity suggesting that the mechanism of this prozone effect was similar to that of a precipitation test. [ABSTRACT FROM AUTHOR]

Various techniques were used to separate canine peripheral blood leucocytes into populations enriched in lymphocytes, polymorphonuclcar leucocytes, phagocytic mononuclear cells (monocytes) and macrophages. Surface markers on each cell population were determined by rosette formation. Fc receptors for IgG and complement receptors (C3b and C3d) were present on PMN, monocytes, macrophages as well as on a sub-population of lymphocytes. Purification of the lymphocytes into T-and B-cell-enriched populations revealed that these receptors were present only on the B lymphocytes and not on the T lymphocytes. In addition, a third lymphocyte population, which did not possess surface immunoglobulin, and Fc receptor but not the complement receptor. None of the cell populations exhibited C4 complement receptors or Fc receptors for IgM. When different cell populations were tested for their ability to form rosettes directly with human type ‘O’ red blood cells it was found that most populations could rosette, suggesting that this technique could not be used as a specific marker for canine T lymphocytes. [ABSTRACT FROM AUTHOR]

An effective vaccine against enteric bovine coronavirus (BCV) must be able to induce mucosal immunity. We recently described the construction of recombinant human adenovirus type 5 (hAd5) carrying the BCV haemagglutinin-esterase (HE) gene in the early transcription region 3 of the adenovirus genome. In this study, we examined the induction of systemic and mucosal immune responses to the hAd5 vector carrying the BCV HE gene (AdBcHE) following intranasal or enteric immunization of cotton rats. Regardless of the route of administration, mucosal immunization wiih AdBcHE induced significant levels of anti-HE IgG antibodies in serum. In addition, following intranasal immunization with AdBcHE, significant levels of anti-HE IgA antibodies were found in lung washes of immunized cotton rats. Furthermore, the specific anti-HE antibodies in sera and mucosal secretions efficiently neutralized BCV infectivity in vitro. T-cell proliferation and cell-mediated cytotoxic responses against the BCV HE were elicited in the spleen of intranasally immunized animals. The results demonstrate that mucosal immunization with AdBcHE is capable of inducing both systemic and mucosal immunity to the BCV HE. These immune responses may be important in protecting animals from BCV infection. [ABSTRACT FROM AUTHOR]

Non-major histocompatibility complex (MHC) restricted cytotoxicity is an important part of the immune reaction mounted in response to bovine herpes virus type 1 (BHV-1) infection. In this study, we evaluated the effect of BHV-1 infection on the ability of lung parenchyma leucocytes (LPL), cranial tracheobronchial lymph node cells (BLNC) and peripheral blood mononuclear leucocytes (PBML) to mediate this function. While LPL from non-infected calves mediated cytotoxicity against BHV-1-infected cells, a similar activity could not be detected in PBML or BLNC. in contrast, both LPL and PBML from naive calves could mediate cytotoxicity against K562 target cells but only after activation with interleukin-2 (IL-2). BLNC were unable to kill K562 cells. Infection of calves with BHV-1 enhanced the ability of LPL and PBML to kill BHV-1-infected cells. This enhancement was detected as early as Day 1 after infection in LPL whereas it could only be detected in PBML 8 days after infection. The results demonstrate that the leucocyte population present at the site of infection was able to mediate a potentially important antiviral function and that this function was enhanced rapidly in response to infection. Thus LPL-mediated cytotoxicity may be an important mechanism for the recovery from BHV-1 infection. [ABSTRACT FROM AUTHOR]

Cattle were immunized with glycoprotein IV (gIV) from bovine herpes virus-1 (BHV-1). Groups of five animals were then given either 2, 3, 4, or 5 doses of interleukin-2 (IL-2) (0.5 μg/kg) at 12-hr intervals. Animals that received no IL-2 exhibited specific immune responses that are typical for BHV-I infection, i.e. enhanced specific cytotoxicity, lymphocyte proliferative responses to gIV, and increased gIV-specific (ELISA) and virus-neutralizing antibodies. Treatment of animals with five doses of IL-2 significantly augmented all of these responses except serum neutralization (P< 0.05). Furthermore, the dose of IL-2 that was selected did not induce any non-specific responses, i.e. hypergamma-globulinaemia, changes in blood chemistry, increased lymphokine-activated killer (LAK) cell activity, changes in mitogen responsiveness or alterations in the phenotypic profile of circulating lymphocytes. Nor were there any clinical changes associated with IL-2 therapy (e.g. depression, pyrexia, diarrhea). Animals that were treated with less than five doses of IL-2 also exhibited elevated immune responses, but they were not significantly different from untreated immunized controls. Interestingly, animals given five doses of IL-2 responded to minor contaminants present in the gIV preparation. This allows speculation that this dose regimen of IL-2 is not only a potent adjuvant for conventional vaccine immunizing doses, but will also allow the use of minute quantities of antigen for immunization. [ABSTRACT FROM AUTHOR]

Non-specific suppressor-cell activity was generated in bovine peripheral-blood leucocytes by treatment with various concentrations of concanavalin A. The activity was expressed against syngeneic and allogeneic responder cells. The involvement of the macrophage-monocyte was found to be necessary for the induction of suppressor cells. After depletion of monocytes from peripheral-blood leucocyles, by sequential plastic adherence and passage through Sephadex G- 10 columns, the inducible suppressor activity was significantly reduced or completely abolished. Reconstitution with monocytes resulted in renewed activity in a dose-dependent manner. Histocompatibility identity of macrophages and non-adherent cells was not required since allogeneic macrophages reconstituted the response of non-adherent cells to a degree comparable to syngeneic cells. Alveolar macrophages were shown to be even more efficient as assessory cells for suppressor-cell induction than peripheral-blood monocytes. [ABSTRACT FROM AUTHOR]

The temporal relation between a lung infection with bovine herpesvirus-1, suppression of some immune functions, and susceptibility to secondary bacterial infection resulting in fibrinous pneumonia prompted a study to determine the mechanism(s) involved in the apparent immunosuppression. In six independent experiments employing from five to 40 calves, we studied the immunologic parameters of migration of and superoxide anion production by polymorphonuclear neutrophils, lectin-induced lymphocyte proliferation, interleukin-2 production, natural cytotoxicity, interferon and antibody formation, as well as complement activation and hematologic parameters. Chemotaxis of polymorphonuclear neutrophils, natural cytotoxicity, and mitogen response of peripheral blood leukocytes were depressed, whereas superoxide anion generation by polymorphonuclear neutrophils was transiently increased and interleukin-2 production was only marginally affected. The assumption that virus-induced interferon might be a common cause for the various changes could not be substantiated. However, the results did suggest that mechanisms other than lack of T helper cell activity, accessory cell activity of macrophages, or development of suppressor T cells were the cause of suppressed mitogen responses. None of the immunologic parameters appeared to have consistent prognostic value with respect to outcome of the infection. [ABSTRACT FROM PUBLISHER]