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At least 19 recordsLinked to original sources

Protective immunity against Brugia malayi infective larvae in mice. I. Parameters of active and passive immunity.

Protective immunity against infective larvae of Brugia malayi was studied in different strains of mice using various sources of antigens. The following strains of mice were susceptible to infective larvae development for 2 weeks after primary ip challenge: BALB/c, C3H/HeJ, C3H/NeN, C3H/HeJms, C57BL/6Jms, and DDD. In comparison to gerbils, BALB/c mice developed stronger resistance to infective larvae after immunization with irradiation attenuated larvae or with killed microfilariae (mf). However, killed mf failed to enhance resistance in C3H/HeJ mice, although C3H/HeN mice were strongly protected and C3H/HeJms mice were protected to a lesser degree by this antigen. Extracts of mf with phosphate buffered saline and sodium dodecyl sulfate both induced high levels of resistance in BALB/c mice. Transfer of resistance from BALB/c mice immunized with attenuated infective larvae to naive mice was accomplished at a high level at protection with nylon wool nonadherent spleen cells (T cells) but not with adherent cells treated with anti-Thy 1.2 serum and complement. In contrast, sera from immunized mice were much less protective.

Animals↗

Vaccination with the major secretory protein of Legionella induces humoral and cell-mediated immune responses and protective immunity across different serogroups of Legionella pneumophila and different species of Legionella.

In a previous study, we demonstrated that immunization of guinea pigs with the major secretory protein (MSP) of Legionella pneumophila, serogroup 1 induced humoral and cell-mediated immune responses to MSP and protective immunity against lethal aerosol challenge with this serogroup of L. pneumophila. Although serogroup 1 L. pneumophila cause most cases of Legionnaires' disease, other serogroups of L. pneumophila and species of Legionella cause many cases. In this study, we have examined if immunization with MSP induces humoral and cell-mediated immune responses and protective immunity across different serogroups of L. pneumophila and species of Legionella. By immunoblot analysis, MSP from L. pneumophila serogroup 1 (Lp1 MSP), L. pneumophila serogroup 6 (Lp6 MSP), and Legionella bozemanii (Lb MSP) shared common epitopes recognized by guinea pig anti-Lp1 MSP antiserum. These MSP molecules, however, were not identical as they had different apparent m.w. Immunization of guinea pigs with MSP induced strong cell-mediated immune responses across the different serogroups and species, as indicated by splenic lymphocyte proliferation and cutaneous delayed-type hypersensitivity in response to both homologous and heterologous MSP. Immunization with MSP induced strong protective immunity across two serogroups of L. pneumophila; overall, 9 survived aerosol challenge with L. pneumophila serogroup 1 compared to 0 of 12 (0%) sham-immunized control animals (p = 3 x 10(-4), Cochran-Mantel-Haenzel chi 2 statistic for pooled data). Immunization with MSP also induced protective immunity across species of Legionella but protection was species-specific. Whereas immunization with Lb MSP induced protective immunity against L. pneumophila, neither immunization with Lp1 MSP nor immunization with Lb MSP induced protective immunity against L. bozemanii, which produces MSP. Not surprisingly, immunization with MSP did not induce protective immunity against MSP-negative Legionella micdadei. In the case of both L. bozemanii and L. micdadei, immunization with a sublethal dose did confer protective immunity to aerosol challenge indicating that these species do contain immunoprotective components. This study demonstrates that immunization with MSP induces humoral and cell-mediated immune responses across different serogroups of L. pneumophila and species of Legionella, but that the capacity of MSP immunization to induce protective immunity is species-specific. Nevertheless, an MSP vaccine has the potential to induce protective immunity against the great majority of cases of Legionnaires' disease.

Aerosols↗

Effect of nasal immunization with protective antigen of Bacillus anthracis on protective immune response against anthrax toxin.

Anthrax toxin consists of three proteins: protective antigen (PA), lethal factor (LF) and edema factor (EF). PA in combination with LF (lethal toxin) is lethal to mammalian cells and is the major component of human anthrax vaccine. Immunization with PA elicits the production of neutralizing antibodies that form a major component of the protective immunity against anthrax. Recent reports have shown that neutralizing antibody titres can serve as a reliable surrogate marker for protection against anthrax. In the present study, the use of non-invasive routes such as bare skin and nose for immunization with PA on its protective immune response was investigated. Mice were inoculated intranasally (i.n.), subcutaneously (s.c.) or through the skin on days 0, 15 and 28 with purified PA. Intranasal and subcutaneous immunization with PA resulted in high IgG ELISA titers. The predominant subclass in each group was IgG1. High titres of IgA were observed only in i.n. immunized mice. In a cytotoxicity assay these sera protected J774A.1 cells from lethal toxin challenge. The results suggest that non-invasive nasal immunization may be useful in improving vaccination strategies against anthrax.

Administration, Intranasal↗

Protective immunity to genital herpes simplex [correction of simpex] virus type 2 infection is mediated by T-bet.

We show, for the first time, that the transcription factor T-bet, which is implicated in IFN-gamma production, is required for the induction of vaccine-induced antiviral immune protection. T-bet was found to be important in both the innate and acquired immune protection against genital HSV-2 infection. T-bet(-/-) and T-bet(+/+) mice were infected vaginally with HSV-2 and examined daily for disease and mortality. T-bet(-/-) mice had significantly higher virus titers than T-bet(+/+) mice following a primary HSV-2 infection, and succumbed significantly earlier to the infection. This result was associated with an impaired NK cell cytotoxic capacity and NK cell-mediated IFN-gamma production in the T-bet(-/-) mice. To assess the induction of acquired antiviral immune protection, mice were vaccinated with an attenuated virus before infection. Vaccinated T-bet(-/-) mice could not control viral replication following an HSV-2 challenge and had significantly higher virus titers and mortality rates than vaccinated T-bet(+/+) mice that remained healthy. The impaired acquired immune protection in T-bet(-/-) mice was associated with a significantly decreased HSV-2-specific delayed-type hypersensitivity response and a significantly reduced HSV-2-specific IFN-gamma production from CD4(+) T cells. However, T-bet deficiency did not impair either the IFN-gamma production or the cytotoxic capacity of HSV-2-specific CD8(+) T cells. We conclude that T-bet plays a crucial role in both the innate defense and the generation of vaccine-induced immunity against genital HSV-2 infection in mice.

Animals↗

Human immunoglobulin G mediates protective immunity and identifies protective antigens against larval Strongyloides stercoralis in mice.

Protective immunity to larval Strongyloides stercoralis in mice has been shown to be dependent on antibody, complement, and granulocytes. The goals of the present study was to determine the following: (1) whether human serum could passively transfer immunity to mice, (2) the mechanism by which the serum mediated killing, and (3) whether the antigens (Ags) recognized by the protective human antibody could induce protective immunity in mice. Immunoglobulin G (IgG) from a S. stercoralis-seropositive individual passively transferred immunity to mice. The antibody required granulocytes, but not eosinophils, and complement activation to kill the larvae. Antibody-dependent cellular cytotoxicity was not required for larval killing. Immunization of mice with soluble larval Ags isolated by use of the protective immune IgG resulted in protective immunity. In conclusion, immunity could be transferred to mice by IgG from immune humans, and Ags identified by the immune human IgG induced protective immunity in mice, which thereby suggests their possible use in a vaccine against this infection.

Animals↗

DNA immunization confers protective immunity on mice challenged intravaginally with herpes simplex virus type 2.

The immunogenicity and protective efficacy of a nucleic acid vaccine encoding the herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) gene under the control of the CMV immediate early gene promoter was examined. Mice immunized three times by intramuscular injection with the vaccine developed an HSV specific IgG but not IgA antibody response detectable in both serum and vaginal secretions. In addition, antigen-specific cellular immune responses were detected in splenic lymphocytes isolated from DNA immunized animals. Immunization reduced virus replication in the genital tract following a lethal intravaginal HSV-2 challenge. Furthermore, symptomatic genital HSV disease was reduced in immunized mice and the animals were completely protected from death. We conclude that a nucleic acid vaccine expressing HSV-1 gD induced both humoral and cell mediated immune responses in mice which proved highly protective against disease following virus challenge.

Animals↗

Induction of humoral immune response and protective immunity in chickens against Salmonella enteritidis after a single dose of killed bacterium-loaded microspheres.

Formalin-inactivated Salmonella enteritidis phage type 4 strain 119/95 (SE) was encapsulated in biodegradable poly (DL-lactide co-glycolic acid) PLGA; (65:35) microspheres by a modified water-in-oil-in-water (w/o/w) double-emulsion solvent extraction/evaporation technique. These SE-loaded microspheres (SE-MS) were porous and spherical in shape with diameters of 0.4-10 microm and 20-80 microm in two preparations. SE-MS were subsequently used to vaccinate specific-pathogen-free chickens in a single dose in order to investigate the potency of a single-dose vaccination in inducing immune responses and protective immunity. In Experiment 1, 4-wk-old chickens that were vaccinated intramuscularly with 20-80-microm SE-MS generated long lasting (over 6 mo) and persistently high serum anti-SE immunoglobulin (Ig)G antibody response. In Experiment 2, 2-wk-old chickens were vaccinated orally with 0.4-10-microm or intramuscularly with 20-80-microm SE-MS and challenged with 10(9) colony-forming units of homologous SE strain at 6 wk postvaccination. When challenged intramuscularly, one each of the orally vaccinated (n = 10) and the intramuscularly vaccinated birds (n = 10) showed clinical signs and death, whereas all of the nonvaccinated control birds (n = 12) were sick and 11 of them were killed. When challenge was via oral route, 26.1% of cloacal swabs and 24.0% of organs (liver, spleen, and cecum) collected from orally vaccinated birds (n = 35) were positive for SE, comparable to 27.9% of feces and 18.7% of organs from the intramuscularly vaccinated birds (n = 35). These figures were significantly lower than those for nonvaccinated birds (n = 30) from which 59.3% of feces and 44.0% of organs tested SE positive (P < 0.05). The humoral immune response was also determined after vaccination with a single dose. The intramuscular vaccination elicited higher serum IgG response than oral administration, but the latter elicited a significant intestinal mucosal IgA antibody response. This is the first evidence that chickens vaccinated with killed SE-loaded PLGA microspheres, intramuscularly and orally in a single dose, developed systematic and local immune responses, thereby conferring protective immunity.

Administration, Oral↗

Induction of protective immunity in dogs to infection with Dirofilaria immitis using chemically-abbreviated infections.

Four dogs were immunized against Dirofilaria immitis infection by a series of 3 larval infections which were each subsequently terminated by ivermectin treatment. Two control dogs received ivermectin treatment alone. Following the final ivermectin treatment, dogs were challenged with infective larvae by subcutaneous inoculation, both free and contained within diffusion chambers. Three weeks after larval challenge the chambers were removed and live larvae were enumerated. Seven months after challenge dogs were killed and necropsied to collect and count adult D. immitis. Chambers recovered from immunized dogs had 63% fewer larvae than chambers from control dogs. At necropsy, control dogs had a mean of 28.5 adult worms whereas the immunized animals had an average of 0.5 worms (range 0-2). Sera collected from immune dogs throughout the study had elevated antibody levels to third- and fourth-larval stage antigens. Significant levels of immune protection were achieved with this immunization regimen. The data suggest that a multiple-stage parasite killing occurs in immune animals. It was not possible to associate immune protection with any of the 5 antigen subsets.

Animals↗

Vaccination with Legionella pneumophila membranes induces cell-mediated and protective immunity in a guinea pig model of Legionnaires' disease. Protective immunity independent of the major secretory protein of Legionella pneumophila.

We have examined the capacity of Legionella pneumophila membranes to induce cell-mediated immune responses and protective immunity in a guinea pig model of Legionnaires' disease. Guinea pigs immunized by aerosol with L. pneumophila membranes developed strong cell-mediated immune responses to L. pneumophila membranes as demonstrated by cutaneous delayed-type hypersensitivity and in vitro splenic lymphocyte proliferation. Guinea pigs immunized by aerosol or by subcutaneous inoculation with L. pneumophila membranes developed strong protective immunity against lethal aerosol challenge with L. pneumophila. Overall, in six independent experiments, 39 of 49 (80%) guinea pigs immunized with L. pneumophila membranes survived challenge compared with 2 of 40 (5%) sham-immunized controls (P = 2 x 10(-13). In contrast, guinea pigs immunized by aerosol with formalin-killed L. pneumophila did not develop either a strong cell-mediated immune response to L. pneumophila antigens or protective immunity to lethal aerosol challenge. The capacity of L. pneumophila membranes to induce protective immunity was independent of the major secretory protein of L. pneumophila, which we previously demonstrated is an immunoprotective molecule. Purified L. pneumophila membranes did not contain detectable major secretory protein (MSP) on immunoblots; immunization of guinea pigs with L. pneumophila membranes did not induce anti-MSP antibody; and guinea pigs developed comparable protective immunity after immunization with membranes from either an L. pneumophila strain that secretes the major secretory protein or an isogenic mutant that does not. This study demonstrates that (a) immunization with L. pneumophila membranes but not formalin-killed L. pneumophila induces strong cell-mediated immune responses and protective immunity, (b) L. pneumophila membranes contain immunoprotective molecules distinct from the major secretory protein of L. pneumophila, and (c) L. pneumophila membranes have potential as a vaccine against Legionnaires' disease.

Aerosols↗

DNA immunization induces protective immunity against B-cell lymphoma.

Idiotypic determinants of the immunoglobulin expressed on the surface of B-cell lymphomas are tumor-specific antigens (TSAs), which can be targeted by immunotherapy. Immunization with DNA constructs encoding the idiotype (ld) of a murine B-cell lymphoma induced specific anti-ld antibody responses and protected mice against tumor challenge. Use of DNA encoding an ld/GM-CSF (idiotype/granulocyte-macrophage colony-stimulating factor) fusion protein improved vaccine efficacy, and xenogeneic immunoglobulin constant region determinants were required for immunogenicity. These results indicate that DNA may be a simple and efficacious means of inducing immune responses against a weak, otherwise unrecognized tumor antigen, provided that additional stimuli are included with the DNA.

Animals↗

Macrophage activation as an immune correlate to protective immunity against schistosomiasis in mice immunized with an irradiated, cryopreserved live vaccine.

Immune responses against Schistosoma mansoni were evaluated in C57BL/6 mice injected with one of two populations of irradiated schistosomules, the larval preparations differing only in the degree of freezing-induced damage sustained upon cryopreservation. Mice injected with larvae which successfully withstood cryopreservation showed a significant reduction in worm burden following cercarial challenge. No protection was achieved in mice which received larvae damaged by a suboptimal thawing rate. Parallel comparison of several humoral and cellular responses in mice which received either inoculum revealed that induction of activated macrophages and production of macrophage-activating lymphokine activity were the strongest correlates to development of protective immunity. Protected mice also showed marginal 30-min skin test reactivity and weak but transient 24-h delayed-type hypersensitivity to a soluble adult worm preparation. In contrast, indistinguishable levels of circulating antibodies to soluble and tegumental antigens developed in the two immunization groups, and antigen-stimulated lymphocyte blastogenic responses were strong and essentially equivalent in magnitude. These studies strongly suggested that in this new model for investigating anti-schistosome effector mechanisms, responses contributing to the development of activated macrophages may be essential for induction of protective immunity.

Animals↗

The epitope recognized by a monoclonal antibody in influenza A virus M2 protein is immunogenic and confers immune protection.

Based on our previous study that the monoclonal antibody (mAb) 8C6 recognizing the extracellular domain of influenza A virus M2 protein (M2e) could passively induce protective immunity in mice, epitope mapping was performed in this study. A series of eight mutated M2e were constructed and expressed. It was found in immunoblotting assay that 8C6 could not bind to two of the mutated M2e proteins, which suggested the VETPIR epitope (aa7-12) in M2e for mAb 8C6. More important, EVETPIRN-peptide (aa6-13) conjugated immunogen induced high M2e specific antibody titer (1:25,600) in mice after booster immunization, and provided mice significantly 40% higher survival rate compared with the control group in challenge assay (p=0.0215), which suggested the EVETPIRN-epitope was immunogenic and actively conferred immune protection to some extent. In addition, sequence comparison suggested the EVETPIRN sequence (aa6-13) was highly conserved in all human influenza A strains. All these data suggested the EVETPIRN sequence in M2e could be one new target for influenza vaccine design.

Amino Acid Sequence↗

Effects of intranasal immunization on protective immunity against otitis media.

It has been reported that intranasal immunization can induce mucosal immune responses. However, the efficacy of intranasal immunization on otitis media caused by non-typeable Haemophilus influenzae (NTHi) is not yet elucidated. Mice were intranasally, orally, intratracheally or intraperitoneally immunized with outer membrane protein (OMP) isolated from NTHi, and antigen-specific immune responses were determined by enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immuno-spot assay (ELISPOT). Cytokine production from splenic CD4+ T cells was examined by ELISA. Following the immunization, the clearance of NTHi from the nasal and nasopharyngeal cavity was examined. OMP-specific IgA antibody titers in nasal washes and the numbers of specific IgA-producing cells in nasal passages were significantly increased in intranasally immunized mice. Cytokine analysis showed that interferon-gamma (IFN-gamma) and interleukins IL-6 and IL-10 were predominantly produced from CD4+ T cells. The clearance of NTHi was significantly enhanced in the intranasal immunization group. Intranasal immunization is an effective vaccination regimen for the induction of OMP-specific mucosal immune responses.

Animals↗

Suppression of immune response and protective immunity to a Japanese encephalitis virus DNA vaccine by coadministration of an IL-12-expressing plasmid.

IL-12 plays a central role in both innate and acquired immunity and has been demonstrated to potentiate the protective immunity in several experimental vaccines. However, in this study, we show that IL-12 can be detrimental to the immune responses elicited by a plasmid DNA vaccine. Coadministration of the IL-12-expressing plasmid (pIL-12) significantly suppressed the protective immunity elicited by a plasmid DNA vaccine (pE) encoding the envelope protein of Japanese encephalitis virus. This suppressive effect was associated with marked reduction of specific T cell proliferation and Ab responses. A single dose of pIL-12 treatment with plasmid pE in initial priming resulted in significant immune suppression to subsequent pE booster immunization. The pIL-12-mediated immune suppression was dose dependent and evident only when the IL-12 gene was injected either before or coincident with the pE DNA vaccine. Finally, using IFN-gamma gene-disrupted mice, we showed that the suppressive activity of the IL-12 plasmid was dependent upon endogenous production of IFN-gamma. These results demonstrate that coexpression of the IL-12 gene can sometimes produce untoward effects to immune responses, and thus its application as a vaccine adjuvant should be carefully evaluated.

Animals↗

Effector lymphoid tissue and its crucial role in protective immunity.

It is often argued that T cell-mediated immunity to secondary infection is dependent on the 'accelerated' responses of memory T cells in lymph nodes. However, new evidence points to a crucial role for effector memory T cells, which are resident in peripheral tissues, in immune protection. These T cells, which reside in peripheral tissues, are not necessarily bound by an anatomical structure and can be present at many sites. Collectively, they represent a third functional tissue of the immune system, uniquely specialized to mediate protective immunity. We propose that the paradigm 'effector lymphoid tissue' needs to be articulated and developed as a focus of new research to describe and understand the unique role this tissue has in protective immunity.

Animals↗