Nasal Inoculation Research Articles

Daily nasal inoculation with the insulin gene ameliorates diabetes in mice

The present study examined the feasibility of liposome-mediated gene transfer via nasal administration, for treating insulin-dependent diabetes mellitus. The rat insulin gene was packed under control of the CMV promoter, complexed with DC-chol/DOPE-based liposomes and administered daily via the nasal route in mice made severely diabetic by streptozocin. Sustained expression of the insulin gene was achieved and insulinopenia, ketonuria and death were prevented. Hyperglycemia and body weight reduction were significantly suppressed without evidence of hypoglycemia throughout the experimental period. RT-PCR and FISH analysis indicated that insulin was produced in the alveolar epithelial cells of the lung. Liposome-mediated in vivo gene transfer via nasal administration may provide an efficacious route for delivery of hormonal and other gene products into the blood stream.

Pneumococcal carriage results in ganglioside-mediated olfactory tissue infection.

Streptococcus pneumoniae cause considerable morbidity and mortality, with persistent neurological sequelae, particularly in young children and the elderly. It is widely assumed that carriage occurs through direct mucosal colonization from the environment whereas meningitis results from invasion from the blood. However, the results of published studies can be interpreted that pneumococci may enter the brain directly from the nasal cavity by axonal transport through olfactory nerves. This hypothesis is based on findings that (i) teichoic acid of the pneumococcal cell wall interact with gangliosides (GLS), (ii) the interaction of GLS with cholera toxin leads to axonal transport through the olfactory nerves into the brain, and (iii) viruses enter the brain through axonal transport into olfactory nerves. After nasal inoculation, we observe high numbers of pneumococci in nasal washes and the olfactory nerves and epithelium. Significant numbers of pneumococci also infected the olfactory bulbs, brain, and the trigeminal ganglia. The absence of bacteremia in this model makes it unlikely that the bacteria entered the brain from the blood stream. Recovery of colony-forming units from the brain, lungs, olfactory nerves, and epithelium and nasal washes was inhibited by incubating pneumococci with GLS before nasal inoculation. These findings, confirmed by PCR and immunohistochemistry, support a GLS-mediated process of infection and are consistent with pneumococci reaching the brain through retrograde axonal transport.

Safety and immunogenicity of a peptide containing the cross-neutralization epitope of HPV16 L2 administered nasally in healthy volunteers

Amino acid (aa) 108–120 of L2 protein of human papillomavirus (HPV) type 16 contains a cross-neutralization epitope against genital HPV. We designed a placebo-controlled trial in healthy adults to evaluate the safety and immunogenicity of a synthetic peptide consisting of the aa 108–120 of HPV16 L2 (L2-108/120) region. A total of 13 volunteers were given nasal inoculations with 0.1 ( n=5) or 0.5 mg ( n=5) doses of the peptides or placebo ( n=3) without adjuvant at weeks 0, 4, and 12. Sera were collected before inoculation and at 6, 16 and 36 weeks. The inoculation caused no serious local and systemic complications. The inoculation generated anti-L2 antibodies binding to both HPV16 and 52 L1/L2-capsids in four of the five recipients in the 0.5 mg group. Sera of the four recipients showed neutralizing activities against HPV16 and 52. Serological responses to the peptides were not found in the 0.1 mg group and the placebo group recipients. This study suggests the L2-108/120 peptide is tolerable in humans and has the potential as a broad-spectrum prophylactic vaccine against genital HPV.

Nasal immunization with diphtheria toxoid conjugated-CD52 core peptide induced specific antibody production in genital tract of female mice.

The common mucosal immune system (CMIS) has developed as a barrier for the numerous encounters between the host and various pathogens. It is possible to exploit this system to induce secretion of IgA antibody which inhibits sperm penetration in the female genital tract. In this study, the immunogenicity of a human sperm surface antigen (CD52) introduced by intranasal immunization was investigated with a view to developing a contraceptive vaccine. A synthetic peptide corresponding to CD52 core peptide (GQNDTSQTSSPS) was prepared and conjugated with diphtheria toxoid (DT) as a carrier protein. The immunogen was given to mice with DOTAP:cholesterol liposome adjuvant intranasally, followed by determination of Ig and IgA class antibody levels in the sera and vaginal washes. The CD52 core peptide elicited IgA class as well as Ig antibodies both in the sera and vaginal secretions after intranasal immunization. An additional nasal inoculation after decrease of the antibody titer raised the antibody level to its highest level during the experiment. These results indicate that the CMIS could induce Ig and IgA class antibodies reactive to CD52 core peptide in the female genital tract. Intranasal immunization of a sperm-specific antigen would be a promising regimen for a safe and easy contraceptive vaccine.

Nasal and otologic effects of experimental respiratory syncytial virus infection in adults

Purpose: Upper respiratory tract viral infections continue to cause substantial patient morbidity and complications including sinusitis, otitis media, and pneumonia. This study was conducted to more clearly define the extent and frequency of nasal and otologic effects of respiratory syncytial virus infection in healthy adult volunteers. Materials and Methods: Thirty-two healthy, susceptible adult volunteers were cloistered for a 9-day period. During this time, subjects underwent nasal inoculation with respiratory syncytial virus. Monitoring included daily self-assessment of general health, as well as nasal and otologic symptoms. Objective measurements of nasal and otologic function included expelled nasal secretion weight, saccharin-dye mucociliary clearance, sonotubometry, tympanometry, and physical examination. A nasal lavage was done each morning, and fluids were submitted for viral detection. Twenty-one days after viral inoculation, all subjects had convalescent blood samples drawn for assay of virus-specific antibody titres. Results: Eighteen subjects (56%) became infected with the challenge as determined by either viral shedding (47%) or antigen detection (41%) from the nose or a 4-fold rise in virus-specific antibody titer (34%). Infected subjects more frequently reported adverse nasal (congestion, rhinorrhea) and general symptoms (fever, malaise, illness). By day 6, only 46% of infected subjects had normal middle ear pressure (>−100 mm H2O). Nasal secretion also increased substantially after infection. No patterned changes in mucociliary clearance or sonotubometry occurred, and no subjects developed otitis media. Conclusions: Nasal inoculation of healthy, susceptible adult volunteers with respiratory syncytial virus results in detectable infection in only about half of the subjects challenged. Infected subjects experience substantial symptoms and signs of a viral upper respiratory tract illness. As in our previous studies using rhinovirus and influenza A virus, respiratory syncytial virus disrupted the maintenance of normal middle ear pressures. These findings provide further support for the relationship between viral upper respiratory tract infections and otitis media. (Am J Otolaryngol 2002;23:70-75. Copyright 2002, Elsevier Science (USA). All rights reserved.)

A new intra-NALT route elicits mucosal and systemic immunity against Moraxella catarrhalis in a mouse challenge model

Mucosally administered antigens are often poorly immunogenic due to the difficulty of transporting antigens through the mucosal epithelium. We investigated a new route of intranasal-associated lymphoid tissue (intra-NALT) administration of antigens to circumvent the antigen transportation barrier. A comparative study was carried out on mice administered with killed whole cells of Moraxella catarrhalis strain 25238 plus cholera toxin (CT) by intra-NALT injection and nasal inoculation. Both routes induced significant elevations of several isotype antibodies against strain 25238 in saliva, lung lavage, and serum as measured by an enzyme-linked immunosorbent assay (ELISA). Most of these antibodies were paralleled by the numbers of their corresponding antibody forming cells in mucosal or systemic lymphoid tissues. However, intra-NALT injection elicited higher levels of immunoglobulin (Ig) A and IgG in saliva, IgA and IgG in lung lavage, and IgG and IgM in sera than nasal inoculation ( P≤0.05). In addition, both routes generated significant reductions of bacteria in lungs following an aerosol challenge with strain 25238 in a mouse model of pulmonary clearance. Once again, intra-NALT route showed better bacterial clearance in mouse lungs than nasal inoculation ( P<0.01). These results demonstrate that intra-NALT administration of antigens is a convenient and effective route for mucosal immunization that elicits improved mucosal and systemic immunity. This new route can be used as a model to study mucosal antigens or vaccine candidates for antigen activation and interaction with the NALT that is one of major inductive sites for common mucosal immune system.

Mucosal vaccination with recombinantly attenuated staphylococcal enterotoxin B and protection in a murine model.

Previous work in our laboratory revealed that mice parenterally vaccinated with recombinantly attenuated staphylococcal enterotoxin (SE) or toxic shock syndrome toxin 1 develop protective antibodies against a lethal intraperitoneal (i.p.) toxin challenge. This study investigated the efficacy of nasal and oral immunizations with an SEB vaccine (SEBv) toward an i.p. or mucosal (via an aerosol) toxin challenge. Both vaccination routes, with the immunoadjuvant cholera toxin (CT), elicited comparable SEB-specific immunoglobulin A (IgA) and IgG levels in saliva. Nasal or oral inoculations also generated SEB-specific IgA, IgG, and IgM in the serum, but the nasal route yielded higher specific IgG titers. SEBv alone, when given nasally or orally, did not induce any detectable SEB-specific antibody. Mice vaccinated mucosally were protected against a 50% lethal dose of wild-type SEB given i.p. or mucosally, thus demonstrating that nasal or oral administration of this SEBv, with CT, elicits systemic and mucosal antibodies to SEB that protect against SEB-induced lethal shock.

Effects of an experimentally induced rhinovirus cold on sleep, performance, and daytime alertness

Study objectives: There is accumulating evidence that the common cold produces impairments in psychomotor vigilance. This has led some investigators to hypothesize that such illnesses may also have disruptive effects on sleep. While several self-report studies suggest that viral illness may influence sleep parameters, no studies have assessed polysomnographically recorded sleep following viral infections. Design: Parallel control group comparison. Setting: Sleep laboratory in a large urban medical center. Participants: Twenty-one men and women with susceptibility to the rhinovirus type 23. Interventions: Nasal inoculation with rhinovirus type 23. Measurements: Polysomnographically recorded sleep for five nights (2300–0700 h) post-viral inoculation. Twice daily (1030 and 1430 h) performance assessment during each experimental day using auditory vigilance and divided attention tasks. A multiple sleep latency test (MSLT) was performed daily for the duration of the study. Results: In symptomatic individuals, total sleep time decreased an average of 23 min, consolidated sleep decreased an average of 36 min, and sleep efficiency was reduced by an average of 5% during the active viral period (experimental days/nights 3–5) compared with the incubation period. Psychomotor performance was impaired. These changes were significantly greater than those observed in asymptomatic individuals. Conclusions: The common cold can have detrimental effects on sleep and psychomotor performance in symptomatic individuals during the initial active phase of the illness.

Effects of allergic inflammation of the nasal mucosa on the severity of rhinovirus 16 cold

Background: Despite the strong association of asthma exacerbations with rhinovirus (RV) infection, inoculation of asthmatic subjects with RV only causes small changes in lower airway function, suggesting that RV infection is not itself sufficient to provoke asthma exacerbations. Objective: Our purpose was to test whether allergic inflammation increases the airway response to RV infection. Methods: We compared the severity of RV type 16–induced colds in 2 groups of 10 subjects with allergic rhinitis. One group received 3 nasal challenges with allergen and the other received challenges with placebo over the week before nasal inoculation with RV type 16 (4000 tissue culture infective dose 50% per subject). Subjects kept symptom diaries and were assessed with spirometry, methacholine challenge, nasal lavage, and sputum induction on days 2, 4, 7, 10, 15, and 30 after inoculation. Results: The 2 groups developed equal rates of infection (90%), similar cold symptoms (Jackson score median [interquartile range], 11 [6-33] vs 20.5 [6-42] for allergen and placebo groups respectively, P = .54), and similar changes in cellular profile and in IL-6 and IL-8 concentrations in nasal lavage fluid and induced sputum after RV inoculation. The incubation period was significantly longer in the allergen group (2.5 [1-5.5] vs 1 [1-1] day, P = .03) and the duration of cold symptoms was shorter (5 [4-7] vs 8.5 [6-10] days, P = .008). We also found an inverse correlation between the percent of eosinophils in nasal lavage fluid before inoculation and the severity of cold symptoms (r = –0.58, P = .008). Conclusion: In subjects with allergic rhinitis, augmented nasal allergic inflammation before inoculation with RV type 16 does not worsen the severity of cold symptoms but delays their onset and shortens their duration. (J Allergy Clin Immunol 2000;105:923-32.)

Effect of clarithromycin on experimental rhinovirus-16 colds: a randomized, double-blind, controlled trial

PURPOSE: Macrolide antibiotics are frequently prescribed to patients with symptoms of a common cold. Despite their lack of proven antiviral activity, macrolide antibiotics may have anti-inflammatory actions, such as inhibition of mucus secretion and production of interleukins 6 and 8 by epithelial cells. Because the symptoms of rhinovirus colds are attributed to the inflammatory response to infection, we studied the effects of treatment with clarithromycin on the symptomatic and inflammatory response to nasal inoculation with rhinovirus. SUBJECTS AND METHODS: We performed a prospective, double-blind, controlled trial in 24 healthy subjects who were seronegative for antibodies to rhinovirus-16. Subjects were randomly assigned to receive either clarithromycin (500 mg) or trimethoprim-sulfamethoxazole (800/160 mg, as a control antibiotic) twice a day for 8 days, beginning 24 hours before inoculation with rhinovirus-16. RESULTS: All 12 subjects in each group were infected and developed symptomatic colds. The groups did not differ in the intensity of cold symptoms (median [25th to 75th percentile] score in the clarithromycin group of 25 [5 to 33] versus 21 [11 to 26] in the trimethoprim-sulfamethoxazole group, P = 0.86), weight of nasal secretions (25 g [8 to 56 g] versus 12 g [5 to 28 g], P = 0.27), or decline in nasal peak flow during the 8 days following viral inoculation. In both groups, similar and significant increases from baseline were observed in the numbers of total cells and neutrophils, and in the concentrations of interleukins 6 and 8, in nasal lavage fluid during the cold. The changes that we observed did not differ from those in an untreated historical control group. CONCLUSIONS: We conclude that clarithromycin treatment has little or no effect on the severity of cold symptoms or the intensity of neutrophilic nasal inflammation in experimental rhinovirus-16 colds.

Intranasal Administration of Influenza Vaccines

AbstractThis review article focuses on intranasal immunisation against influenza,although it also encompasses antigen uptake and processing in the nasopharyngealpassages, host defence from influenza and current influenza vaccination practices.Improvement of current vaccination strategies is clearly required; current proceduresinvolve repeated annual injections that sometimes fail to protect the recipient. It isenvisaged that nonpercutaneous immunisation would be more attractive to potentialvaccinees, thus improving uptake and coverage. As well as satisfying noninvasivecriteria, intranasal influenza immunisation has a number of perceived immunologicaladvantages over current procedures. Perhaps one of the greatest attributes of thisapproach is its potential to evoke the secretion of haemagglutinin-specific IgAantibodies in the upper respiratory tract, the main site of viral infection. Inactivated influenza vaccines have the advantage that they have a long historyof good tolerability as injected immunogens, and in this respect are possibly morelikely to be licensed than attenuated viruses. Inert influenza vaccines are poormucosal immunogens, requiring several administrations, or prior immunologicalpriming, in order to engender significant antibody responses. The use of vaccinedelivery systems or mucosal adjuvants serves to appreciably improve theimmunogenicity of mucosally applied inactivated influenza vaccines. As is the casewhen they are introduced parenterally, inactivated influenza vaccines are relativelypoor stimulators of virus-specific cytotoxic T lymphocyte activity following nasalinoculation. Live attenuated intranasal influenza vaccines are at a far moreadvanced stage of clinical readiness (phase III versus phase I). With the use of liveattenuated vaccines, it is possible to stimulate mucosal and cell-mediatedimmunological responses of a similar kind to those elicited by natural influenzainfection. In children, recombinant live attenuated cold-adapted influenza viruses arewell tolerated. Moreover, cold-adapted influenza viruses usually stimulate protectiveimmunity following only a single nasal inoculation. Safety of recombinant liveattenuated cold-adapted influenza viruses has also been demonstrated in high riskindividuals with cystic fibrosis, asthma, cardiovascular disease and diabetes mellitus.They are not suitable for immunising immunocompromised patients, however, andare poorly efficacious in individuals with pre-existing immunity to strains closelyantigenically matched with the recombinant virus. According to the reviewedliterature, it is apparent that intranasal administration of vaccine as an aerosol issuperior to administration as nose drops. The information reviewed in this papersuggests that nasally administered influenza vaccines could make a substantialimpact on the human and economic cost of influenza.

Generation of protective immune responses to plague by mucosal administration of microsphere coencapsulated recombinant subunits

We have investigated noninvasive immunization to plague. Recombinant subunit antigens, F1 and V from Yersinia pestis, were coencapsulated in biodegradable poly(l-lactide) microspheres and intranasally administered to mice over a range of dose levels. Proteins retained antigenicity during, and postmicroencapsulation as evidenced by immunoblotting and capture enzyme-linked immunosorbent assay protocols. Supporting the rationale that a subunit antigen based vaccine for plague should contain both the F1 and V antigens, we observed that systemic antibody titres to V were improved by concomitant nasal immunization with F1. Conversely, serum titres to F1 were unaffected by the presence of V in the nasal inoculum. Interestingly, intramuscular injection of F1 augmented humoral immunity to nasally applied V antigen, suggesting that F1 adjuvantizes nasally instilled V even when introduced at a spatially distinct location. Although the magnitude of the specific serum response to nasally applied microspheres and equivalent doses of soluble subunits was not always directly proportional to administered dose and frequency of dosing, generally coencapsulated antigens evoked higher titred serum antibody responses. Also, when T-cell recall indices were measured they were found to be maximum in microsphere vaccinees. As few as two appropriately timed nasal inoculations of coencapsulated F1 and V afforded complete protection from >100 LD50’s inhalational challenge with virulent Y. pestis. These data expand on previous findings from our laboratories, providing further insight into the mechanics of safeguarding mice from plague through nasal immunization. Further, these results demonstrate that in a murine model, solid protection from pneumonic plague can be engendered by two intranasal administrations of appropriately formulated recombinant proteins.

Cattle immune responses to tetanus toxoid elicited by recombinant S. typhimurium vaccines or tetanus toxoid in alum or Freund's adjuvant

Cattle were immunised orally, nasally or subcutaneously with either S. typhimurium 4/74 aroA − aroD − or S. typhimurium 4/74 htrA-based live vaccines expressing Fragment C (TetC) of tetanus toxin from plasmid pTetnir15. Oral inoculation with S. typhimurium 4/74 aroA − aroD − - (pTetnir15) elicited mucosal anti-TetC IgA but no measurable systemic humoral responses to TetC. Subcutaneous inoculation with the same strain elicited both mucosal IgA and systemic anti-TetC IgG1 responses. Nasal inoculation did not elicit any detectable anti-TetC responses. Oral delivery of S. typhimurium htrA − proved fatal in inoculated animals. None of the animals inoculated with either mutant S. typhimurium developed detectable T cell proliferative responses to the guest antigen. Cattle were also inoculated with tetanus toxoid adsorbed in alum or emulsified in Freund's complete adjuvant. Animals inoculated subcutaneously with Ttox emulsified in FCA developed systemic IgG1 and IgG2 antibody, while animals inoculated with Ttox adsorbed in alum developed systemic IgG1 but little IgG2 to Ttox. Both of these groups of animals developed measurable TetC-specific proliferative T cell responses that were associated with the production of IFNγ.

Immunological responses to nasal delivery of free and encapsulated tetanus toxoid: studies on the effect of vehicle volume

In light of growing interest in the intranasal route as a non-invasive mode of immunisation, we have investigated the relationship between the volume of liquid instilled into the nasal passages and the development of subsequent immunological responses. Groups of six mice were intranasally immunised with soluble or microsphere encapsulated tetanus toxoid on days 1, 14 and 28 of the experiment. Microsphere suspensions and tetanus toxoid solutions were nasally instilled in two different volumes of buffer (10 or 50 μl). Nasal instillation of microspheres in 10 μl of buffer generated statistically depressed ( P<0.001) tertiary serum anti-toxoid IgG responses in comparison to animals immunised with 10 or 50 μl of soluble vaccine, or 50 μl of microsphere suspension. Relative to other treatments, nasal inoculation of encapsulated toxoid suspended in 50 μl generated statistically ( P<0.05) superior levels of specific IgG and IgA antibodies in day 49 lung wash samples. When radiolabelled microspheres were nasally instilled into mouse nares in 50-μl volumes of buffer, a significant portion of the dose (48%) entered the lungs ( P<0.001), whereas more particles remained in the nasal passages when a smaller (10 μl) volume of suspension was given ( P<0.001). These biodistribution and immunological data indicate that to generate optimal bronchopulmonary and systemic responses in concert following nasal administration, microparticulated vaccines should be administered with a delivery device that targets the formulation to distal regions of the nasal passages and the lower respiratory tract.

Induction of protective immunity for Bordetella pertussis by nasal inoculation of pertussis vaccine in mice

Although nasal vaccination has emerged as an interesting alternative to intramuscular or oral vaccination, knowledge is scarce about the immune responses after such immunization. In the present study, we inoculated purified Pertussis Toxin (PT) and Filamentous Haemagglutinin (FHA) with or without adjuvant (kayexalate), or Diphtheria acellular Pertussis Tetanus (DaPT) combined vaccine to mice intranasally three times every four weeks to investigate the references of the immunoresponses between nasal and intramuscular vaccination. The levels of pertussis specific serum IgG antibodies (Abs) and secretory IgA Abs in the nasal wash were measured by ELISA, and cytotoxic T cell activities were examined by proliferative response, and compared with the result from intramuscular inoculation. We also studied the efficacy of adjuvant in the nasal vaccination. The intramuscular inoculation of pertussis vaccine induced serum IgG antibodies and cellular immunity against PT and FHA, but did not induce local IgA antibodies. On the other hand, the nasal inoculation induced both serum and local antibody responses. Moreover, it also induced significant cellular immunity to pertussis antigen. In nasal vaccination, the inoculation with adjuvant was superior to inoculation without adjuvant for the induction of both humoral and cellular immunity.

Azithromycin, Chlamydia pneumoniae , and Intimal Thickening

To the Editor: In the February 24, 1998, issue of Circulation , Muhlestein et al1 reported on cholesterol-fed rabbits that had repeated nasal inoculations of Chlamydia pneumoniae and whose thoracic aortas showed intimal thickness 3 months later. The authors concluded that weekly treatment with azithromycin for 7 weeks after infectious exposure prevents accelerated intimal thickening. We appreciate the importance of the study and see the implications of its results; however, the conclusion in its present form raises some comments. First, we would be interested in the data on whether and to what extent neointima had been seen at the intermediate time points of weeks 3 and 10. The question remains whether azithromycin treatment really prevents intimal thickening because of its antichlamydial effect. It is important to note that it is uncertain precisely when neointima formation in response to the …

Airway hyper-responsiveness to neurokinin A and bradykinin following Mycoplasma pneumoniae infection associated with reduced epithelial neutral endopeptidase.

To determine whether mycoplasma infection produces airway hyper-responsiveness to tachykinins and bradykinin and, if so, to elucidate the role of neutral endopeptidase (NEP), isolated hamster tracheal segments were studied under isometric conditions in vitro. Nasal inoculation with Mycoplasma pneumoniae potentiated contractile responses to neurokinin A and bradykinin, causing a leftward shift of the dose-response curves to a lower concentration by 1 log unit for each agonist, whereas there was no response with acetylcholine. Pretreatment of tissues with the NEP inhibitor phosphoramidon augmented neurokinin A- and bradykinin-induced contractions in saline-treated control tissues, but did not further potentiate the responsiveness in M. pneumoniae-infected tissues. NEP activity in the tracheal epithelium, but not in epithelium-denuded tissues, was decreased in infected animals. These results suggest that M. pneumoniae infection causes airway bronchoconstrictor hyper-responsiveness to neurokinin A and bradykinin and that this effect may be associated with an inhibition of epithelial NEP activity.

Airway hyperresponsiveness to histamine in mycoplasmal infection: role of histamine N-methyltransferase

To elucidate the modulatory role of histamine-degrading enzymes in airway constrictor responses in mycoplasmal infection, we studied hamster tracheal segments under isometric conditions in vitro. Nasal inoculation with Mycoplasma pneumoniae potentiated the contractile responses to histamine but not to methacholine. Pretreatment of tissues with the histamine N-methyltransferase inhibitor SKF 91488 abolished the infection-induced potentiation, whereas, the diamine oxidase inhibitor aminoguanidine had no effect. The histamine N-methyltransferase but not diamine oxidase activity in tracheal tissues was decreased in infected animals. These results suggest that M. pneumoniae causes airway hyperresponsiveness to histamine probably through a reduction of endogenous histamine N-methyltransferase activity.

In vivo antiinfluenza virus activity of Kampo medicine Sho-Seiryu-To through mucosal immune system

The Kampo (Japanese herbal) medicine, Sho-seiryu-to, which has traditionally been used for the treatment of colds and bronchial asthma, showed potent antiinfluenza A and B virus activity through augmentation of production of antiviral IgA antibody in the nasal and bronchoalveolar cavities of mice when administrated orally before viral infection. Sho-seiryu-to also showed antiinfluenza virus activity against A virus H1N1 subtype infected in aged mice (approximately 6 months old) with an increase of antiviral IgA antibody in the bronchoalveolar wash of the treated mice by similar administration. When mice infected with mouse nonadapted influenza A virus H3N2 subtype before 14 days were secondarily infected with mouse adapted A/PR/8 (H1N1) virus and administered Sho-seiryu-to orally after the second infection, replication of the virus in both nasal and bronchoalveolar cavities was significantly inhibited. Sho-seiryu-to had no effect on the mice which were not primed with mouse nonadapted virus when administered after the infection of mouse-adapted A/PR/8 virus. Oral administration of Sho-seiryu-to caused increment of viral-specific IgA antibody secreting cells in mouse nasal lymphocyte. Sho-seiryu-to also augmented IL-2 receptor beta chain+ T-cells in Peyer's patch of the infected mice. Sho-seiryu-to also significantly reduced viral titer in the nasal washes of the infected ovalbumin-sensitized bronchial asthma model mice. Oral administration of Sho-seiryu-to before and after vaccination significantly augmented hemagglutination-inhibiting antibody in the serum by nasal inoculation of influenza HA vaccine, and significantly augmented nasal antiviral IgA antibody and bronchoalveolar and serum antiviral IgG antibodies even after secondary vaccination although induction of antiviral antibody by intranasal vaccination was insufficient without Sho-seiryu-to. These results suggest that Sho-seiryu-to is able to prevent influenza virus infection by cross-protection of subtypes of influenza A virus and B virus. Sho-seiryu-to is also useful for the treatment of influenza virus infection in hosts with a history of influenza virus infection and/or influenza vaccination and allergic pulmonary inflammation, such as bronchial asthma, and can be used as an adjuvant to nasally inoculated influenza HA vaccine.

A Meta-analysis of Zinc Salts Lozenges and the Common Cold

In the United States, the common cold has been estimated to cost more than $3.5 billion a year. Despite several randomized clinical trials, the effect of treating colds with zinc salts lozenges remains uncertain because of conflicting results. To conduct a meta-analysis of published randomized clinical trials on the use of zinc salts lozenges in colds using a random effects model. Eight clinical trials of treating adults with zinc salts lozenges were identified. After excluding 2 studies that used nasal inoculation of rhinovirus, 6 trials were combined and analyzed. The summary odds ratio for the presence of any cold symptoms at 7 days was 0.50 (95% confidence interval, 0.19-1.29). Despite numerous randomized trials, the evidence for effectiveness of zinc salts lozenges in reducing the duration of common colds is still lacking.