Increased susceptibility of purinergic receptor-deficient mice to lung infection with Pseudomonas aeruginosa

Purinergic receptors are expressed throughout the respiratory system in diverse cell types. The efficiency of mucus clearance in the airways, the cascade leading to tissue injury, and inflammation are modulated by autocrine/paracrine release of nucleotides and signaling by purinergic receptors. We assessed the role of purinergic receptors in innate host defense of the lung in vivo by infecting mice deficient in P2Y1, P2Y2, or both receptors with intratracheal instillation of Pseudomonas aeruginosa. After P. aeruginosa challenge, all double knockout (P2Y1/P2Y2-/-) mice succumbed within 30 h of challenge, whereas 85% of the wild-type mice survived. Thirty-three percent of wild-type mice survived beyond 96 h. Single knockout mice, P2Y1-/-, or P2Y2-/-, exhibited intermediate survivals. Twenty-four hours following intratracheal instillation of a sublethal dose of P. aeruginosa, the level of total protein in bronchoalveolar lavage fluid was 1.8-fold higher in double knockout than in wild-type mice (P < 0.04). Total cell count in bronchoalveolar lavage fluids at 4 h and levels of IL-6 and macrophage inflammatory protein-2 in lung homogenates at 24 h postchallenge were significantly reduced in P2Y1/P2Y2-/- mice relative to wild-type mice. These findings suggest that purinergic receptors exert a protective role against infection of the lungs by P. aeruginosa by decreasing protein leak and enhancing proinflammatory cytokine response.     

Effectiveness of enteric immunization in the development of secretory immunoglobulin A response and the outcome of infection with respiratory syncytial virus.

Cotton rats were immunized via intranasal, intradermal, or enteric routes with respiratory syncytial virus (RSV) or a live recombinant vaccinia virus expressing the RSV F glycoprotein (vaccinia F). The animals were tested for the appearance of RSV-specific antibody responses in the serum, bronchoalveolar lavage, and nasal wash after immunization and for virus replication 4 days after intranasal challenge with RSV. RSV antibody response in the serum and respiratory tract was demonstrated in all immunization groups and was significantly increased after intranasal challenge with RSV. Immunoglobulin A (IgA) antibody response in bronchoalveolar lavage fluid after intranasal or enteric immunization was two- to threefold higher than that after intradermal immunization. Nasal-wash IgA antibody response was not significantly different among three immunization groups, although mean antibody titer was the highest in intranasal immunization group. Complete resistance to replication of RSV challenge was observed in the lungs of cotton rats immunized by the intranasal or enteric routes, whereas a low level of replication was detected in the lungs of rats immunized intradermally. Enteric or intradermal immunization conferred partial protection to the upper respiratory tract, but complete protection of the upper respiratory tract was observed in the intranasal immunization group. These observations suggest that while enteric immunization is quite effective in inducing antibody responses in the respiratory tract, the magnitude of antiviral immunity induced in the respiratory tract after intranasal immunization may be superior to that observed after enteric immunization.     

Replicating adenovirus-simian immunodeficiency virus (SIV) recombinant priming and envelope protein boosting elicits localized, mucosal IgA immunity in rhesus macaques correlated with delayed acquisition following a repeated low-dose rectal SIV(mac251) challenge

We have shown that sequential replicating adenovirus type 5 host range mutant human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) recombinant priming delivered first intranasally (i.n.) plus orally and then intratracheally (i.t.), followed by envelope protein boosting, elicits broad cellular immunity and functional, envelope-specific serum and mucosal antibodies that correlate with protection from high-dose SIV and simian/human immunodeficiency virus (SHIV) challenges in rhesus macaques. Here we extended these studies to compare the standard i.n./i.t. regimen with additional mucosal administration routes, including sublingual, rectal, and vaginal routes. Similar systemic cellular and humoral immunity was elicited by all immunization routes. Central and effector memory T cell responses were also elicited by the four immunization routes in bronchoalveolar lavage fluid and jejunal, rectal, and vaginal tissue samples. Cellular responses in vaginal tissue were more compartmentalized, being induced primarily by intravaginal administration. In contrast, all immunization routes elicited secretory IgA (sIgA) responses at multiple mucosal sites. Following a repeated low-dose intrarectal (i.r.) challenge with SIV(mac251) at a dose transmitting one or two variants, protection against acquisition was not achieved except in one macaque in the i.r. immunized group. All immunized macaques exhibited reduced peak viremia compared to that of controls, correlated inversely with prechallenge serum antienvelope avidity, antibody-dependent cellular cytotoxicity (ADCC) titers, and percent antibody-dependent cell-mediated viral inhibition. Both antibody avidity and ADCC titers were correlated with the number of exposures required for infection. Notably, we show for the first time a significant correlation of vaccine-induced sIgA titers in rectal secretions with delayed acquisition. Further investigation of the characteristics and properties of the sIgA should elucidate the mechanism leading to this protective effect.     

Definition of the pulmonary antibody response to ovalbumin following local challenge in systemically immunized rats

The in vivo pulmonary immune response of rats to local stimulation with antigen was assessed by measuring antigen-specific antibody and antibody-secreting cells utilizing enzyme-immunoassay technology. Sprague-Dawley rats were immunized subcutaneously with ovalbumin (OA) emulsified in Freund's incomplete adjuvant, challenged with OA intratracheally on Day 19 and sacrificed 1, 2, 3, or 4 days later. Specific antibody-secreting cells in the lung-associated lymph nodes were enumerated with the ELISA-SPOT assay and antibody concentration in the pulmonary lavage fluids and sera was assessed with the ELISA. The greatest response for each parameter was on Day 2. Cellular infiltration of the lung was minimal. Cellular infiltrates consisted mainly of polymorphonuclear leukocytes and were most numerous in the lavage fluid on Days 1 and 2 and in the lung parenchyma on Day 2 after challenge. Local production versus serum transudation of antibody was evaluated by comparing the levels of OA-specific antibody to albumin in the lavage fluid and serum. The data showed that antibody in the lungs was primarily produced locally.     

Antimicrobial activity of PLUNC protects against Pseudomonas aeruginosa infection

Epithelial antimicrobial activity may protect the lung against inhaled pathogens. The bactericidal/permeability-increasing protein family has demonstrated antimicrobial activity in vitro. PLUNC (palate, lung, and nasal epithelium associated) is a 25-kDa secreted protein that shares homology with bactericidal/permeability-increasing proteins and is expressed in nasopharyngeal and respiratory epithelium. The objective of this study was to determine whether PLUNC can limit Pseudomonas aeruginosa infection in mice. Transgenic mice (Scgb1a1-hPLUNC) were generated in which human PLUNC (hPLUNC) was directed to the airway epithelium with the Scgb1a1 promoter. The hPLUNC protein (hPLUNC) was detected in the epithelium throughout the trachea and bronchial airways and in bronchoalveolar lavage fluid. Bronchoalveolar lavage fluid from transgenic mice exhibited higher antibacterial activity than that from wild type littermates in vitro. After in vivo P. aeruginosa challenge, Scgb1a1-hPLUNC transgenic mice displayed enhanced bacterial clearance. This was accompanied by a decrease in neutrophil infiltration and cytokine levels. More importantly, the overexpressed hPLUNC in Scgb1a1-hPLUNC transgenic mouse airway significantly enhanced mouse survival against P. aeruginosa-induced respiratory infection. These data indicate that PLUNC is a novel antibacterial protein that likely plays a critical role in airway epithelium-mediated innate immune response.     

Oral administration of cholera toxin-Sendai virus conjugate potentiates gut and respiratory immunity against Sendai virus

Successful oral immunization to prevent infectious diseases in the gastrointestinal tract as well as distant mucosal tissues may depend on the effectiveness of an Ag to induce gut immune responses. We and others have previously reported that cholera toxin possesses strong adjuvant effects on the gut immune response to co-administered Ag. To explore further adjuvant effects of cholera toxin, the holotoxin or its B subunit was chemically cross-linked to Sendai virus. The resulting conjugates, which were not infectious, were evaluated for their capacity to induce gut immune responses against Sendai virus after oral administration to mice. Conjugating cholera toxin to virus significantly enhanced the adjuvant activity of cholera toxin compared to simple mixing. Cholera toxin B subunit, however, did not show an adjuvant effect either by itself or conjugated with the virus. Oral administration of the Sendai virus-cholera toxin conjugate was also able to prime for protective anti-viral responses in the respiratory tract. Mice that were orally immunized with the conjugate and intra-nasally boosted with inactivated virus alone showed virus-specific IgA titers in nasal secretions that correlated with protection against direct nasal challenge with live Sendai virus. For comparison, s.c. immunization was also studied. Systemic immunization with the virus-cholera toxin conjugate induced virus-specific antibody responses in serum as well as in the respiratory tract but failed to protect the upper respiratory tract against virus challenge. Systemic immunization plus an intra-nasal boost did, however, confer a variable degree of protection to the upper respiratory tract, which correlated primarily with bronchoalveolar lavage (lung) antibody titers.     

Induction of humoral antibody response by soluble polysaccharide of Cryptococcus neoformans

Mice were immunized with purifiedCryptococcus neoformans soluble polysaccharide, or with the polysaccharide coupled to methylated bovine serum albumin or methylated bovine gamma globulin. The polysaccharide-methylated protein complexes were no more immunogenic than the purified polysaccharide when used without Freund's incomplete adjuvant; however, the methylated protein complexes induced higher levels of antibody than purified polysaccharide when emulsified in the adjuvant. Sera from mice were titrated by passive hemagglutination, and maximum antibody titers were observed 14 to 21 days after immunization. Antibody titers declined rapidly after 14 to 21 days in mice immunized with antigen alone; whereas, animals immunized with cryptococcal antigen emulsified in adjuvant remained at peak levels throughout a six week experimental period. All antigens were immunogenic over a wider dosage range when contained in adjuvant. Individual mice immunized with an adjuvant emulsion of purified polysaccharide varied widely in the amount of antibody produced, with some of the animals producing no detectable antibody.     

Induction of antigen-specific immune responses by oral vaccination with Saccharomyces cerevisiae expressing Actinobacillus pleuropneumoniae ApxIIA

An effective way of inducing both mucosal and systemic immune responses to protect against Actinobacillus pleuropneumoniae serotype 2 Korean isolate was examined in mice by oral immunization using Saccharomyces cerevisiae expressing the ApxIIA protein. The immunogenicity of the yeast-derived ApxIIA antigen was confirmed by the challenge test and ApxIIA-specific IgG antibody response assay. The group subcutaneously immunized with the protein extracted from the yeast expressing ApxIIA showed a higher survival rate after challenging with A. pleuropneumoniae serotype 2 isolate and IgG antibody level in serum than the group injected with that prepared from the yeast harboring vector only. Feeding the yeast expressing ApxIIA to mice induced both systemic and mucosal immune responses against the antigen. ApxIIA-specific IgA antibody titers and the number of IgA-secreting cells of mice vaccinated with S. cerevisiae expressing ApxIIA dose-dependently increased from the third immunization in both intestine and lung (P<0.01). A similar tendency of ApxIIA-specific IgG antibody responses was observed in the sera. The protective efficacy of the oral immunization was then evaluated by a challenge with a minimal lethal dose (MLD, 4.5 x 10(7) CFU/ml) of the A. pleuropneumoniae serotype 2 isolate. Fifty percent of the 30 mg administered group and 30% of the 15 mg administered group survived while none of the mice in the control groups survived after 36 h. These results suggest that feeding animals the yeast expressing the antigen can be an effective strategy to induce protective immune responses against A. pleuropneumoniae infection.     

Protective immunity of Nile tilapia against Ichthyophthirius multifiliis post-immunization with live theronts and sonicated trophonts

Two immunization trials were conducted to evaluate host protection of Nile tilapia, Oreochromis niloticus against Ichthyophthirius multifiliis (Ich). Immunizations were done with live theronts or sonicated trophonts by bath immersion and intraperitoneal (IP) injection. The immunized fish were challenged with theronts 21 days post-immunization in trial I and 180 days post-immunization in trial II. The serum anti-Ich antibody and cumulative mortalities of tilapia were determined after theront challenge. Serum anti-Ich antibody was significantly higher (P<0.05) in tilapia immunized with live theronts by immersion or IP injection or with sonicated trophonts administered by IP injection than tilapia immunized with sonicated trophonts by immersion, with bovine serum albumin by IP injection, or non-immunized controls. Host protection was acquired in fish immunized with live theronts by immersion or IP injection. Tilapia immunized with sonicated trophonts by IP injection were partially protected with a 57-77% survival in both trials. At 180 days post-immunization, serum antibody titers had declined in immunized fish yet they were still able to survive challenge. The protection appears not to be solely depending on serum antibody response against Ich.     

Induction of anti-chlamydial mucosal immunity by transcutaneous immunization is enhanced by topical application of GM-CSF

Transcutaneous immunization (TCI) involves the direct application of antigen plus adjuvant to skin, taking advantage of the large numbers of Langerhans cells and other resident skin dendritic cells, that process antigen then migrate to draining lymph nodes where immune responses are initiated. We have used this form of immunization to protect mice against genital tract and respiratory tract chlamydial infection. Protection was associated with local antibody responses in the vagina, uterus and lung as well as strong Th1 responses in the lymph nodes draining the reproductive tract and lungs respectively. In this study we show that topical application of GM-CSF to skin enhances the numbers and activation status of epidermal dendritic cells. Topical application of GM-CSF also increased the immune responses elicited by TCI. GM-CSF supplementation greatly increased cytokine (IFNgamma and IL-4) gene expression in lymph node and splenic cells compared to cells from animals immunized without GM-CSF. IgG responses in serum, uterine lavage and bronchoalveolar lavage and IgA responses in vaginal lavage were also increased by topical application of GM-CSF. The studies show that TCI induces protection against genital and respiratory tract chlamydial infections and that topical application of cytokines such as GM-CSF can enhance TCI-induced antibody and cell-mediated immunity.     

The effect of splenectomy on the immune responses of rabbits to a soluble protein antigen given parenterally or orally

Splenectomized and sham-operated rabbits were immunized with bovine serum albumin (BSA) intravenously, subcutaneously, or orally. Splenectomy caused a 2-to 4-day delay in antibody synthesis in animals immunized intravenously; this delay corresponded to the time that antibody-producing cells were found mainly in the spleen. By 14 days, the antibody response of the splenectomized intravenously immunized group was similar to that of the sham-operated group. Splenectomy did not diminish the antibody responses of rabbits immunized subcutaneously or orally.Splenectomy had no effect on the capacity of circulating lymphocytes to respond to phytohemagglutinin. Similarly, splenectomy did not alter the capacity of circulating lymphocytes from subcutaneously immunized rabbits to respond to BSA in vitro. In contrast, the presence of detectable circulating antigen-reactive lymphocytes in splenectomized animals was slightly reduced after intravenous immunization, and significantly enhanced after oral immunization.Thus, the spleen of the rabbit is important for the early antibody response to soluble protein antigens given intravenously. These studies suggest that the systemic immunity which follows local antigen stimulation at mucosal surfaces, i.e., oral immunization, may be secondary to the circulation of lymphoid cells sensitized in the lamina propria of the intestine.     

Co-administration of plasmid expressing IL-12 with 14-kDa Schistosoma mansoni fatty acid-binding protein cDNA alters immune response profiles and fails to enhance protection induced by Sm14 DNA vaccine alone

Schistosomiasis is an endemic disease that affects 200 million people worldwide. DNA-based vaccine is a promising strategy to induce protective immunity against schistosomiasis, since both humoral and cellular immune responses are involved in parasite elimination. In this study, we evaluated the ability of Sm14 cDNA alone or in association with a plasmid expressing murine interleukin (IL)-12 to induce protection against challenge infection. Mice were immunized with four doses of the DNA vaccine and the levels of protection were determined by worm burden recovery after challenge infection. Specific antibody production to rSm14 was determined by ELISA, and cytokine production was measured in splenocyte culture supernatants stimulated with rSm14 and in bronchoalveolar lavage of vaccinated mice after challenge infection. DNA immunization with pCI/Sm14 alone induced 40.5% of worm reduction. However, the use of pCI/IL-12 as adjuvant to pCI/Sm14 immunization failed to enhance protection against challenge infection. Protection induced by pCI/Sm14 immunization correlates with specific IgG antibody production against Sm14, Th1 type of immune response with high levels of interferon (IFN)-gamma and low levels of IL-4 in splenocyte culture supernatants and in bronchoalveolar lavage after challenge infection. IL-12 co-administration with pCI/Sm14 induced a significant production of nitric oxide in splenocyte culture supernatants and also lymphocyte suppression, with reduced percentage of T cells producing IFN-gamma and tumor necrosis factor-alpha.     

Intranasal vaccination using interleukin-12 and cholera toxin subunit B as adjuvants to enhance mucosal and systemic immunity to human immunodeficiency virus type 1 glycoproteins

We have investigated the induction of protective mucosal immunity to human immunodeficiency virus type 1 (HIV-1) isolate 89.6 by intranasal (i.n.) immunization of mice with gp120 and gp140 together with interleukin-12 (IL-12) and cholera toxin subunit B (CTB) as adjuvants. It was found that both IL-12 and CTB were required to elicit mucosal antibody responses and that i.n. immunization resulted in increased total, immunoglobulin G1 (IgG1), and IgG2a anti-HIV-1 antibody levels in serum; increased total, IgG1, IgG2a, and IgA antibody expression in bronchoalveolar lavage fluids; and increased IgA antibody levels in vaginal washes. Levels of anti-HIV-1 antibodies in both sera and secretions were higher in groups immunized with gp140 than in those immunized with gp120. However, only gp120-specific mucosal antibodies demonstrated neutralizing activity against HIV-1 89.6. Taken together, the results show that IL-12 and CTB act synergistically to enhance both systemic and local mucosal antibody responses to HIV-1 glycoproteins and that even though gp140 induces higher antibody titers than gp120, only gp120-specific mucosal antibodies interfere with virus infectivity.     

Early production of IL-17 protects against acute pulmonary Pseudomonas aeruginosa infection in mice

Interleukin-17 (IL-17) is involved in protection against extracellular bacteria. However, IL-17 is likely to be deleterious to a host with chronic pulmonary Pseudomonas aeruginosa infection. The role of IL-17 during acute pulmonary P. aeruginosa infection remains unknown. Here, we evaluated the role that IL-17 plays in acute pulmonary P. aeruginosa infection and the source of the interleukin. The production of IL-17 increased rapidly after acute pulmonary P. aeruginosa infection in mice. We subsequently examined the role of IL-17 in acute infection and found 100 times more bacteria in the bronchoalveolar lavage fluid of mice treated with an IL-17-neutralizing antibody compared with the IgG(2a) -treated mice after 16 h of infection. The main infiltrating cells in the anti-IL-17-treated mice were lymphocytes rather than neutrophils. Consistently, more tissue damage and pathological changes in the lung were observed in the anti-IL-17-treated mice. We also found that Th17 cells are one of the sources of IL-17. We conclude that the early production of IL-17 plays a protective role during acute pulmonary P. aeruginosa infection in mice and that Th17 cells are one of the sources of IL-17 during acute pulmonary P. aeruginosa infection. Altogether, IL-17 and Th17 cells contribute to the pathogenesis of acute pulmonary P. aeruginosa infection in vivo.     

SARS-CoV-2重组S1和S蛋白疫苗诱导保护性免疫的研究*

目的:评价新型冠状病毒(SARS-CoV-2)重组S1蛋白和S蛋白疫苗对SARS-CoV-2的免疫保护效果。方法:将SARS-CoV-2重组S1蛋白和S蛋白分别联合氢氧化铝佐剂以0.1 μg/只、1 μg/只、5 μg/只、10 μg/只不同剂量接种6~8周BALB/c纯系健康雌性小鼠。第二次免疫后采血通过酶联免疫吸附试验(ELISA)检测血清中IgG抗体效价,通过假病毒中和试验比较免疫小鼠血清对SARS-CoV-2野生型株(WT)、英国株(B.1.1.7)、巴西株(P.1)、印度株(B.1.617.2)、Mu毒株(B.1.621)和南非株(501Y.V2-1)六种假病毒毒株中和活性效价,取脾细胞通过酶联免疫斑点技术(ELISpot)检测免疫小鼠的细胞免疫水平。结果:SARS-CoV-2重组S和S1蛋白都能诱导小鼠产生较强的IgG抗体水平。免疫S1蛋白的小鼠血清对SARS-CoV-2野生型株、英国株、巴西株有明显的中和活性,免疫S蛋白的小鼠血清除了对SARS-CoV-2野生型株、英国株、巴西株有明显中和活性之外,对印度株也有明显的中和活性,两种蛋白质免疫的小鼠血清均对野生型株中和效果最强。S蛋白免疫的小鼠脾细胞能够显著诱导出γ干扰素(IFN-γ)和白介素-4(IL-4)的产生。S蛋白诱导产生的IgG抗体、中和抗体、细胞免疫水平均高于S1。结论:SARS-CoV-2重组S蛋白疫苗能够诱导产生较强的保护性免疫应答。     

Effect of immunization of channel catfish with inactivated trophonts on serum and cutaneous antibody titers and survival against Ichthyophthirius multifiliis

Two trials were conducted to determine the effect of immunization of channel catfish with inactivated trophonts on serum and cutaneous antibody titers and survival against Ichthyophthirius multifiliis Fouquet (Ich). In trial I, catfish were immunized intraperitoneally (IP) with: 1) 1% formalin-inactivated trophonts, 2) 3% formalin-inactivated trophonts and 3) freeze-thawed trophonts. Positive and negative control catfish were immunized with live theronts and 5% bovine serum albumin (BSA), respectively. At day 14, 28 and 50 post-immunizations, no statistical difference was noted in serum or cutaneous anti-Ich antibody titers to formalin-inactivated trophonts or freeze-thawed trophonts. The survival of catfish challenged with live theronts ranged from 33.3% to 43.3% for the formalin-inactivated or freeze-thawed trophonts at 50 d post-immunization. The survival of catfish immunized with live theront and BSA was 93.3 and 0%, respectively. In trial II, catfish were IP immunized with sonicated trophonts at doses of 1) 5 trophonts or 10.2 microg protein g(-1) fish, 2) 10 trophonts or 20.4 microg protein g(-1) fish, 3) 20 trophonts or 40.8 microg protein g(-1) fish, and 4) 5% BSA as the control. Fish immunized with 10 or 20 trophonts g(-1) fish showed highest serum (1/210 to 1/480) and cutaneous antibody titers (1/48 to 1/52), respectively, at 22 d post-immunization and survival (63.3-60.0%). The fish immunized with 5 trophonts g(-1) fish had titers of 1/52 and 1/12 for serum and cutaneous antibody and survival of 23.3%. BSA immunized catfish had background titers and a survival of 6.7%. There was a significant correlation between doses of sonicated trophonts used to immunize and catfish survival (correlation coefficient = 0.859, p < 0.01). These results indicate that doses of sonicated trophonts, but not formalin-inactivated or freeze-thawed trophonts provided both serum and cutaneous antibody responses and survival to live trophont challenge.     

Protective effect of a corpuscular polyvalent Pseudomonas aeruginosa vaccine in generalized chronic Pseudomonas aeruginosa infection in mice with cyclophosphamide-induced leukopenia

The prophylactic effect of immunization with P. aeruginosa polyvalent corpuscular vaccine has been shown on the model of P. aeruginosa generalized chronic infection in mice with leukopenia induced by the intraperitoneal injection of cyclophosphamids. This effect is manifested by the increased resistance of the animals to sublethal doses of P. aeruginosa strain, as well as by more intense general and specific immunological responses in the infected animals (the increase of specific antibody titers, the number of leukocytes in the blood serum and the phagocytic activity of the cells of peritoneal exudate).     

Human anti-Pseudomonas aeruginosa outer membrane proteins IgG cross-protective against infection with heterologous immunotype strains of P. aeruginosa.

In order to develop an effective means to treat and prevent Pseudomonas aeruginosa infections, we have purified P. aeruginosa outer membrane protein (Oprs)-specific human IgG antibody using a large-scale affinity column. In this study, we investigated the cross-protective activity of the purified anti-Oprs IgG against various immunotype strains of P. aeruginosa. The anti-Oprs IgG reacted with Oprs isolated from seven Fisher-Devlin immunotype strains of P. aeruginosa and was able to promote opsonophagocytic killing of all seven immunotype strains by human phagocytic cells. Administration of 500 microg anti-Oprs IgG to mice raised the LD50 of the P. aeruginosa strains by 8-250-fold, indicating the protective capacity against heterologous P. aeruginosa strains as well as homologous strains. In contrast, despite high titers against P. (aeruginosa Oprs, total serum IgG isolated from burn patient sera was no better than normal serum IgG in protecting mice from infection with P. aeruginosa. These data demonstrate that the affinity-purified human anti-Oprs IgG could afford protection against heterologous immunotype P. aeruginosa strains and provide a rationale to use anti-Oprs IgG as an adjunct for treatment of P. aeruginosa infections in humans.     

Plasmodium chabaudi: Humoral and cell-mediated responses of immunized mice

Antigen preparations of Plasmodium chabaudi parasites enriched in merozoites and schizonts, obtained from in vitro culture, and combined with saponin protected C57BL/6J mice from P. chabaudi infection as judged by reduced primary parasitemias and recrudescences. Sera passively transferred from immunized and untreated mice after a challenge infection were more protective in recipients than serum from normal mice. Mice treated with antilymphocyte serum during immunization did not develop as strong an immunity to infection as did controls treated with normal serum. Immunized mice had depressed delayed-type hypersensitivity reactions to malarial antigen but increased serum titers of malarial antibody (measured by imniunofluorescence) after challenge with P. chabaudi when compared to immunized mice which remained unchallenged. The protective activity of sera from various groups of mice did not necessarily correlate with the serum antibody titers.     

Intranasal immunization with a replication-deficient adenoviral vector expressing the fusion glycoprotein of respiratory syncytial virus elicits protective immunity in BALB/c mice

Human respiratory syncytial virus (RSV) is a serious pediatric pathogen of the lower respiratory tract worldwide. There is currently no clinically approved vaccine against RSV infection. Recently, it has been shown that a replication-deficient first generation adenoviral vector (FGAd), which encodes modified RSV attachment glycoprotein (G), elicits long-term protective immunity against RSV infection in mice. The major problem in developing such a vaccine is that G protein lacks MHC-I-restricted epitopes. However, RSV fusion glycoprotein (F) is a major cytotoxic T-lymphocyte epitope in humans and mice, therefore, an FGAd-encoding F (FGAd-F) was constructed and evaluated for its potential as an RSV vaccine in a murine model. Intranasal (i.n.) immunization with FGAd-F generated serum IgG, bronchoalveolar lavage secretory IgA, and RSV-specific CD8+ T-cell responses in BALB/c mice, with characteristic balanced or mixed Th1/Th2 CD4+ T-cell responses. Serum IgG was significantly elevated after boosting with i.n. FGAd-F. Upon challenge, i.n. immunization with FGAd-F displayed an effective protective role against RSV infection. These results demonstrate FGAd-F is able to induce effective protective immunity and is a promising vaccine regimen against RSV infection.