SEARCH · PubMed Health

Results for “Administration, Intranasal”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources

PubMed1999

Exacerbation of influenzavirus pneumonia by intranasal administration of surfactant in a mouse model.

Although surfactant-secreting type II alveolar cells have been shown to be damaged during influenzavirus pneumonia, little is known about the effects of surfactant replacement therapy. We have developed a mouse influenza model, in which viral infection can be localized to the upper respiratory tract or to both the upper and lower respiratory tract depending on the volume (rather than infectious dose) of intranasal inocula of influenzavirus. In this model, only mice infected with a large inocula die with massive infection in the lung. Using this model, we unexpectedly found that intranasal administration of surfactant dramatically exacerbated influenzavirus infection causing fatal disease even in mice inoculated with a small inocula. This exacerbation resulted from enhancement of intrabronchial and intraalveolar spread of virus, as confirmed by immunohistochemical detection of viral antigen in lungs. Assuming this experimental model in mice recapitulates naturally occurring disease in humans, extreme caution is warranted in surfactant-replacement treatment of influenzavirus pneumonia in humans.

Administration, Intranasal↗

PubMed1997

HPLC determination of ITF 188 and its metabolite ITF 1078 in urine after intranasal administration of new heparin salt ITF 1300 to dogs.

Heparin salt ITF 1300 in which low molecular weight heparin is salified with a new counterion, di-[3-(N,N-dibutylamino)]propyl carbonate (ITF 188), was selected for the pharmacological development. A specific, sensitive and reproducible HPLC method for the determination of ITF 188 and its alcoholic metabolite ITF 1078 in urine was developed. The method was employed for the study of urinary excretion of the counterion after intranasal administration of ITF 1300 to dogs. The total amount of ITF 188 and ITF 1078 found in urine within 72 hours after the nasal instillation of ITF 1300 accounts for about 5% of the administered dose.

Administration, Intranasal↗

PubMed1998

Intranasal administration of human immunodeficiency virus type-1 (HIV-1) DNA vaccine with interleukin-2 expression plasmid enhances cell-mediated immunity against HIV-1.

DNA vaccine against human immunodeficiency virus type-1 (HIV-1) can induce substantial levels of HIV-1-specific humoral and cell-mediated immunity. To develop more potent HIV-1 DNA vaccine formulations, we used a murine model to explore the immunomodulatory effects of an interleukin-2 (IL-2) expression plasmid on an HIV-1 DNA vaccine following intranasal administration of the combination. When the vaccine and expression plasmid were incorporated into cationic liposomes and administered to mice, the HIV-1-specific delayed-type hypersensitivity response and cytotoxic T lymphocyte activity were significantly increased. Restimulated immune lymphoid cells showed enhanced production of both IL-2 and interferon-gamma and reduced secretion of IL-4. The level of total antibody to HIV-1 antigen was not greatly changed by coadministration of the DNA vaccine and IL-2 expression plasmid. An analysis of serum HIV-1-specific IgG subclasses showed a significant drop in the IgG1/IgG2a ratio in the group that received the plasmid-vaccine combination. These results demonstrate that the IL-2 expression plasmid strongly enhances the HIV-1-specific immune response via activation of T helper type-1 cells.

Adjuvants, Immunologic↗

PubMed2005

Elicitation of neutralizing antibodies by intranasal administration of recombinant vesicular stomatitis virus expressing human immunodeficiency virus type 1 gp120.

Recombinant viral vectors are useful tools for AIDS vaccine development. However, expression of HIV-1 envelope genes using viral vectors has not been successful in the induction of potent neutralizing antibodies in vivo. We took advantage of the strong immunogenicity of vesicular stomatitis virus (VSV)-based vector and expressed HIV-1 HXB2 gp120 gene in the recombinant VSV. Our results showed that HIV-1 gp120 protein expressed by the recombinant VSV retained the native conformation of the protein to some degree and was recognized by two well-characterized broad anti-HIV-1 neutralizing monoclonal antibodies b12, 2G12. We further showed that only one time intranasal immunization with the recombinant VSV led to production of anti-HIV-1 anti-sera in mice. In addition, we found that the anti-sera had the ability to neutralize not only HXB2 envelope-pseudotyped HIV-1 viruses but also HIV-1 pseudotyped viruses with JRFL envelopes. These results suggest that HIV-1 gp120 expressed by the recombinant VSV, in combination with the route of intranasal administration, is an effective strategy to evaluate the immunogenicity of HIV-1 envelope protein and its variants in mice.

Administration, Intranasal↗

PubMed1991

Intranasal administration of His-D-Trp-Ala-Trp-D-Phe-LysNH2 (growth hormone releasing peptide) increased plasma growth hormone and insulin-like growth factor-I levels in normal men.

The effects of intranasal and iv administration of His-D-Trp-Ala-Trp-D-Phe-LysNH2 (GHRP) on plasma GH, PRL, LH, FSH, TSH, cortisol, insulin, IGF-I as well as GHRH-like immunoreactivity (LI) levels were examined in 6 healthy male subjects. An iv bolus injection of GHRP(1 micrograms/kg BW) caused a remarkable increase in plasma GH levels with a mean (+/- SE) peak of 54.9 +/- 4.2-micrograms/L. In addition an intranasal administration of GHRP resulted in a significant, dose-related increase in plasma GH with peaks of 39.6 +/- 15.3 micrograms/L at a dose of 30 micrograms/kg BW, 14.1 +/- 5.0 micrograms/L at 15 micrograms/kg BW and 7.5 +/- 5.7 micrograms/L at 5 microgram/kg BW. Plasma PRL and cortisol levels were slightly but significantly increased after iv administration of GHRP, whereas GHRP totally failed to affect plasma TSH, LH, FSH, insulin, blood sugar and GHRH-LI levels. Seven consecutive, intranasal administrations of 15 micrograms/kg BW GHRP every 8h were well tolerated in all subjects examined. During this treatment, GH responsiveness to GHRP was not attenuated by desensitization and plasma IGF-I was increased from 94.5 +/- 5.8 micrograms/L before GHRP to 125.8 +/- 6.0 micrograms/L after repeated GHRP administration. These findings indicate that intranasal administration of GHRP stimulates GH secretion and consequently enhances IGF-I production in normal subjects. If GHRP is demonstrated to be beneficial in the treatment of some patients with GH deficiency, the intranasal route of administration may be more useful than the painful injection because a prolonged period is required for the treatment.

Administration, Intranasal↗

PubMed2000

Event-related brain potentials and working memory function in healthy humans after single-dose and prolonged intranasal administration of adrenocorticotropin 4-10 and desacetyl-alpha-melanocyte stimulating hormone.

Neuropeptides of the adrenocorticotropin/melanocorticotropin (ACTH/MSH) family are most potent modulators of cognitive function. Their neurobehavioral activity is principally encoded in the 4-10 fragment of the ACTH/MSH molecule; in humans, it has been shown to pertain primarily to functions of attentive stimulus/response processing. The aims of this study were (1) to examine the effects of ACTH 4-10 on event-related brain potentials (ERPs) and behavioral indicators of stimulus encoding within the working memory; (2) to compare the effects after a single dose and after prolonged treatment with ACTH 4-10; and (3) to compare the effects of ACTH 4-10 with those of desacetyl-alpha-MSH (i.e., ACTH 1-13 amide), which, like ACTH 4-10, binds to the known brain melanocortin receptors (MC-Rs) but with distinctly higher affinity. Double-blind, placebo-controlled experiments were performed in 60 healthy control subjects. The authors monitored ERPs and reaction times while these subjects performed an auditory vigilance task ("oddball"). Recall was tested on a verbal short-term memory task including different word categories (neutral, rare, food, sex). After a single (1 mg) as well as prolonged intranasal administration (1 mg/day over a period of 6 weeks), ACTH 4-10 enhanced the positive slow wave in ERPs to target stimuli of the vigilance task (p < 0.05), but left classic P3 unaffected. Moreover, single-dose and prolonged administration of ACTH 4-10 increased the rate of false responses during vigilance (p < 0.01). In the short term, ACTH 4-10 also impaired recall of neutral words (p < 0.05). Equimolar doses of desacetyl-alpha-MSH did not influence ERPs, neither after a single dose nor after prolonged treatment. Similar to ACTH 4-10, desacetyl-alpha-MSH increased the error rate during vigilance and acutely impaired the recall of neutral words. The increase in ERP slow-wave positivity, in conjunction with behavioral impairments after treatment with ACTH 4-10, complemented previous results of inferior focusing of attention and a less concise structure of thought after administration of ACTH 4-10. The changes indicated an impairment in differential processing of relevant versus irrelevant contents within the working memory, and, in this regard, might mimic aspects of psychopathologic disturbances of attention and thought processes. Their persistence after prolonged treatment with ACTH 4-10 suggests an activation of mechanisms subserving the consolidation of the peptide's effects. The poor efficacy of desacetyl-alpha-MSH suggests that the known MC-Rs may be irrelevant for mediating cognitive effects of this neuropeptide family.

Administration, Intranasal↗

PubMed1991

Effects of intranasal administration of norethisterone on folliculogenesis, cervical mucus, vaginal cytology, endometrial morphology and reproductive-endocrine profile in women.

The effects of intranasal administration of norethisterone (NET) on menstrual cycle length, folliculogenesis, serum levels of estradiol, FSH, LH and progesterone, vaginal cytology, cervical mucus and endometrial morphology were studied in 8 volunteers (age 28 to 39 years, weighing between 46 and 54 kg). The study period comprised 4 consecutive menstrual cycles. In the first cycle (pretreatment cycle), only the vehicle (alcohol, propylene glycol, water; 3:3:4) was sprayed intranasally (100 microliters in each nostril), using a metered nebulizer, once daily from day 3 to the last day of menstrual cycle. In the next two cycles (treatment cycles), NET (300 micrograms/day) was administered once daily, starting from day one of menstrual cycle, between 9 and 10 a.m. The fourth cycle was a post-treatment cycle in which the volunteers were monitored for recovery. Blood samples (about 5 ml each) were collected once daily from day 8 to 24 and thereafter on alternate days until the last day of cycle during all the 4 cycles. Levels of estradiol, FSH, LH and progesterone were measured in the serum samples by radioimmunoassay methods. Cervical mucus samples and vaginal smears were collected once daily starting from day 7 or 8 of each cycle until the mucus was very scanty. Serial pelvic ultrasonography was performed starting from day 7 or 8 until the growing follicle disappeared or throughout the cycle in case a growing follicular cyst was observed. Endometrial aspirates were collected once around day 22 in each cycle and processed for routine histological examination.

Administration, Intranasal↗

PubMed2006

Intranasal administration of IGF-I improves behavior and Purkinje cell pathology in SCA1 mice.

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expansion of polyglutamine repeat within ataxin-1 protein. Cerebellar Purkinje cells are the primary targets of SCA1 pathology. These cells synthesize insulin-like growth factor-I (IGF-I) and express its receptors during their entire life. The aim of present study was to determine if intranasally administered IGF-I to SCA1 transgenic mice suppresses toxic effects of ataxin-1. Two-week old SCA1 heterozygous animals were randomly divided into two treatment groups of IGF-I (30 and 60 microg IGF-I/animal) and a vehicle-treated control group. The wildtype animals served as normal controls. IGF-I or vehicle was administered at 48 h intervals for the total of 10 doses. Animals were then subjected to rotarod test, sacrificed, brains removed and processed for immunohistochemical and Western blot analysis. Radiolabeled IGF-I and bioactive TAT peptide accumulated in the brains of SCA1 mice following intranasal administration validating the use of intranasal route. SCA1 mice showed SCA1 pathology with impaired motor function and downregulation of calcium binding proteins as compared to wildtype mice. However, 30 and 60 microg IGF-I-treated animals showed improved performance on the rotarod as compared to vehicle-treated SCA1 mice with significant improvement (p < 0.05) on day 3 in 60 microg IGF-I group. The immunohistochemical data further showed partial recovery in the expression of calbindin D28k and protein kinase C-gamma in Purkinje cells in IGF-I-treated SCA1 animals. Our results indicate that suppression of ataxin-1-mediated adverse effects by intranasal IGF-I treatment may be of a therapeutic value to treat SCA1.

Administration, Intranasal↗

PubMed1994

Immunogenicity of recombinant adenovirus-human immunodeficiency virus vaccines in chimpanzees following intranasal administration.

Recombinant adenovirus (Ad)-human immunodeficiency virus (HIV) vaccines expressing HIVIIIB Env and Gag proteins were evaluated for immunogenicity in chimpanzees following intranasal administration. When Ad7-, Ad4-, and Ad5-vectored vaccines were administered sequentially at 0, 24, and 52 weeks, respectively, to three chimpanzees, the inoculations resulted in limited virus replication in the nasopharynx, but extensive Ad-HIV replication occurred in the intestine. High-titered IgG serum antibody responses to Env and Gag that were nonneutralizing were induced following booster administration of Ad4-HIV recombinant viruses. Following the Ad5-HIV booster, low levels of neutralizing antibodies as well as V3 loop antibodies were induced in all three chimpanzees that persisted for several months. Administration of a gp160 subunit vaccine (baculovirus derived) in SAF-m 24 weeks later boosted broadly neutralizing serum antibodies that peaked within 1 month of the injection. Two additional subunit boosters 19 and 37 weeks later were progressively less effective at stimulating serum neutralizing antibody responses. Substantial local immune responses were induced in nasal, vaginal, and salivary secretions following the third Ad-HIV intranasal immunization. These responses were further boosted with the gp160 subunit vaccine, which also stimulated production of rectal antibodies. The predominant responses in all secretions tested were of the IgG isotype, although some IgA responses were also detected. Strong blastogenic responses to HIV recombinant Env and Gag proteins were induced after each immunization.

AIDS Vaccines↗

PubMed2006

Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection.

Attenuated recombinant H5N1 influenza virus was constructed to develop a safe H5N1 influenza vaccine. The immunogenicity and protective effect of the vaccine prepared from haemagglutinin-modified recombinant H5N1 influenza virus was evaluated in mice intranasally co-administered with cholera toxin B subunit containing a trace amount of holotoxin (CTB*), synthetic double-stranded RNA, poly (I:C) or chitin microparticles (CMP) as adjuvants. Intranasal administration of recombinant H5 HA split vaccine with CTB* or poly(I:C) and/or CMP elicited an immunological response with both anti-H5 HA IgA in the nasal wash and anti-H5 HA IgG antibody in the serum, and showed a protective against lethal H5N1 A/Hong Kong/483/97 (HK483) infection. We also demonstrated that intranasal co-administration of antigen with both poly (I:C) and CMP enhanced the expression of Toll-like receptor (TLR) 3, TLR7 in the spleen. These results indicate that poly (I:C) and CMP are highly effective as mucosal adjuvants for use with the nasal H5N1 vaccine.

Adjuvants, Immunologic↗

PubMedDate not supplied

Intranasal administration of midazolam: pharmacokinetic and pharmacodynamic properties and sedative potential.

This study investigated the pharmacodynamic effects and sedative potential of midazolam administered by the intranasal route to adult volunteers. A double-blind, randomized, controlled study was carried out on seventeen healthy, male volunteers to study plasma level changes, sedative effects and variations in vital signs following intranasal administration of 0.2 mg/kg and 0.3 mg/kg doses of midazolam. Eight subjects received 0.2 mg/kg midazolam, seven received 0.3 mg/kg. Each subject rested for 15-20 minutes after placement of vital sign monitors and venipuncture needles before administration of midazolam. Behavior during the rest period was designated as the control so that each subject acted as his own control. Each subject's behavior was assessed on a scale of 1 (asleep) to 8 (excited). Plasma concentrations of midazolam were analyzed using venous blood samples from each of three randomly selected subjects for each of the two doses. Vital signs, monitored continuously, included electrocardiogram, heart rate, blood pressure, respiratory rate and oxygen saturation (SPO2). Plasma concentration of midazolam in both groups maintained adequate sedation levels with each group sustaining favorable sedation conditions from 15-20 minutes to 55-60 minutes. Individual variations of midazolam plasma concentration within the 0.3 mg/kg group were greater than those of the 0.2 mg/kg group. Normal vital sign variations due to the nasal instillation of midazolam were observed in both groups. Some minor respiratory depression was observed in the 0.2 mg/kg group. One instance of severe respiratory depression was observed in the higher dose group. Although both doses of midazolam were effective, no benefit was observed using a dose of 0.3 mg/kg. Indeed, a 0.3 mg/kg intranasal dose of midazolam may actually produce severe respiratory depression.

Administration, Intranasal↗

PubMed1990

Dose-effect study of intranasal administration of growth hormone-releasing hormone-44-NH2 in healthy subjects.

Intranasal (in) administration of GH-releasing hormone-40- (GHRH-40) has been demonstrated to be efficient in stimulating GH secretion at doses equal to or higher than 30 micrograms/kg in man. We performed a dose-response study with GHRH-44-NH2 (GHRH) given by nasal spray and closely monitored local tolerance. Twelve normal young men were given 5 GNRH doses (125, 250, 500, 750, and 1000 micrograms) and placebo in random order according to a latin square design. Mild symptoms of local intolerance, subjective, objective, or both, were noted in the first 20 min after spray in 30 of 72 tests, and a significant difference (P = 0.003) was obtained in their frequency between the group placebo plus the lowest dose and the group of the other doses. The areas under the GH curves were significantly different between the subjects and the doses (by analysis of variance, P = 0.001 and P = 0.025, respectively). Multiple comparison tests showed a significant difference between the 3 highest doses and the placebo (P = 0.005, P = 0.05, and P = 0.02, respectively) and a significant difference between the highest dose and the 2 lowest doses (P = 0.005). By weighted linear regression between GH areas under the curve and GHRH doses the dose-response relationship was established as: y = 1.226x + 457. The magnitude of the GH peaks induced by in GHRH was significantly lower than that induced by iv GHRH. We conclude that in the normal young men tested, who were high responders to GHRH (as demonstrated by iv test), a 500-micrograms dose is sufficient to elicit GH secretion. Local tolerance, although imperfect, appears satisfactory to permit a clinical trial in children.

Administration, Intranasal↗

PubMed2005

Intranasal administration of nerve growth factor (NGF) rescues recognition memory deficits in AD11 anti-NGF transgenic mice.

Nerve growth factor (NGF) delivery to the brain of patients appears to be an emerging potential therapeutic approach to neurodegenerative disease, such as Alzheimer's disease (AD). The intranasal route of administration could provide an alternative to intracere-broventricular infusion and gene therapy. We previously showed that intranasal administration of NGF determined an amelioration of cholinergic deficit and a decrease in the number of phosphotau-positive neurons and of beta-amyloid accumulation in AD11 mice, which express transgenic antibodies neutralizing NGF action and exhibit a progressive Alzheimer-like neurodegeneration. In this study, we report that the Alzheimer-like neurodegeneration in AD11 mice is linked to progressive behavioral deficits in visual recognition memory and spatial memory starting from 4 months of age. To establish whether intranasal administration of NGF, started after the appearance of the first memory deficits, could revert the cognitive deficits in AD11 mice, we assessed the performance of NGF-treated or control AD11 mice in the object recognition test and in a test of memory for place and context. Deficits exhibited by untreated AD11 mice could be rescued by the intranasal administration of NGF. Thus, this route of administration provides a promising way to deliver NGF to the brain in a therapeutic perspective.

Administration, Intranasal↗

PubMed1993

[Intranasal administration of nitroglycerin solution and nitroglycerin spray during general anesthesia].

Nitroglycerin spray is a newly developed nitroglycerin (TNG) form, which delivers 0.3 mg of TNG with each spray emission. We compared the efficacy of intranasal administration of TNG spray and that of TNG solution during general anesthesia. Nineteen patients were randomly assigned to receive either 0.3 mg TNG solution (Solution group) or 0.3 mg TNG spray (Spray group) intranasally. Peak elevation of plasma TNG occurred 2 min after drug administration in both groups, and the plasma level decreased to an ineffective level after 10 min. The plasma TNG of the spray group was significantly higher than that of the solution group for 3 min. Two min after drug administration, systolic blood pressure decreased significantly in both groups, and this level persisted for 10 min. Diastolic blood pressure also decreased in the spray group, but not in the solution group. Heart rate increased significantly in both groups 2 min after drug administration. Oxygen index (PaO2/FIO2) decreased significantly in both groups, and the level persisted 10 min after administration. Although no significant differences were found between two nitroglycerin forms in any of these hemodynamic and respiratory parameters, nitroglycerin spray may have clinical advantages because of reliability in its effect, ready availability, ease of application and high stability.

Administration, Intranasal↗

PubMed1999

Bioavailability of apomorphine following intranasal administration of mucoadhesive drug delivery systems in rabbits.

PURPOSE: The purpose of this study was to investigate both the in vitro and in vivo release of apomorphine from mucoadhesive powder formulations of Carbopol 971P and polycarbophil. METHODS: The in vitro drug release from the mucoadhesive formulations was studied using a modified USP XXII rotating basket. The pharmacokinetics of apomorphine given as a solution was determined after subcutaneous and intranasal administrations to rabbits. The animals also received intranasally the mucoadhesive dosage forms and immediate release lactose powder mixture. Comparisons were made between the salient pharmacokinetic parameters of the different dosage forms. RESULTS: Sustained in vitro drug release was obtained from the mucoadhesive formulations. Apomorphine was absorbed more rapidly in rabbits when administered intranasally than as a subcutaneous injection. The mucoadhesive formulations both gave sustained plasma drug concentrations and bioavailabilities comparable to subcutaneous injections. The times taken to achieve peak plasma drug concentrations from these mucoadhesive formulations were more than three-fold that of lactose. With these mucoadhesive formulations apomorphine lasted longer in the blood. It could be detected for up to 6-8 h compared to approximately 3 h for the other forms of administration. CONCLUSIONS: The nasal bioavailability of powders is higher than that of solutions. Drug release from the mucoadhesive powders was sustained and there was no significant difference between Carbopol 971P and polycarbophil.

Acrylic Resins↗

PubMed1982

Sensitivity of pituitary and corpus luteum responses to single intranasal administration of (D-ser[TBU]6-des-gly-NH2(10)) luteinizing hormone-releasing hormone ethylamide (Buserelin) in normal women.

We have previously shown that intranasal administration of Buserelin (Hoechst AG, Frankfurt, Germany) at mid-luteal phase inhibits progesterone secretion and shortens the luteal phase. In order to determine the best possible use of this medication, we studied the effect of increasing doses (50 to 1500 microgram) of the luteinizing hormone-releasing hormone (LH-RH) agonist administered between days 6 and 12 after the luteinizing hormone (LH) peak on the pituitary response and corpus luteum function. A near-maximal gonadotropin response was obtained at a dose of 200 microgram. Maximal LH stimulation was observed at 4 hours, and serum levels of the hormone remained elevated for at least 14 hours at the two highest doses. Maximal serum follicle-stimulating hormone (FSH) levels were usually observed 2 hours later than for LH, and the response was longer lasting. A 2- to 2.5-fold stimulating of serum progesterone levels was observed at 8 hours for all doses studied. There was a tendency for a dose effect on serum estradiol levels, a 2-fold stimulation being obtained at 14 hours at the highest dose of LH-RH analog. Up to 200 microgram, there was no apparent change in the luteal phase. At the 500-microgram dose, there was a clear tendency for decreased estradiol and progesterone concentrations during the treatment cycle, while at 1000 and 1500-microgram doses steroid levels were clearly inhibited and the luteal phase was shortened by 2.5 days. Posttreatment cycles were normal. Thus the corpus luteum is sensitive to a single high intranasal dose of Buserelin, the luteolytic effect being related to the prolonged gonadotropin response.

Administration, Intranasal↗

PubMed1987

Subcutaneous and intranasal administration of 1-deamino-8-d-arginine vasopressin in the assessment of renal concentration capacity.

Maximum urine concentration capacity was studied in healthy adults using different routes and doses of administration of 1-deamino-8-d-arginine vasopressin (DDAVP)-desmopressin. Plasma levels of DDAVP showed a dose-dependent increase after the subcutaneous but not after the intranasal administration. The effect on urine osmolality was similar but more prolonged after the subcutaneous as compared to the intranasal route. We conclude that subcutaneous injection is a simple and reliable way of administering DDAVP. A dose of 4 micrograms in adults is optimum diagnostically and it corresponds to 20-40 micrograms administered intranasally.

Administration, Intranasal↗

PubMed2002

Induction of protective immunity to bovine herpesvirus type 1 in cattle by intranasal administration of replication-defective human adenovirus type 5 expressing glycoprotein gC or gD.

Replication-defective human adenoviruses type 5 (HAd5) expressing the bovine herpesvirus type 1 (BHV-1) glycoprotein gC or gD under the control of the human cytomegalovirus immediate-early promoter/enhancer (AdCMVgC or AdCMVgD) or the 5' regulatory region of the human desmin gene (AdDESMgC or AdDESMgD) were generated. A preliminary experiment performed on rabbits showed that the intranasal administration of AdCMV elicited higher levels of BHV-1 neutralizing antibodies than the intramuscular administration of AdDESM. The obtained results allowed to select the replication-defective AdCMVgC and AdCMVgD for further assessment of their potential as a recombinant vaccine in cattle. Calves were injected intranasally twice 3 weeks apart with either AdCMVgC or AdCMVgD or a combination of these two recombinants or a commercially available live vaccine for comparison. The highest BHV-1 neutralizing antibody titres were obtained with AdCMVgD followed by the live vaccine and to a lower extent with the combination of the two recombinants (AdCMVgC+AdCMVgD). Calves were protected against intranasal BHV-1 challenge performed 3 weeks after the second immunization. In view of the obtained results, recombinant HAd5 may be developed as an intranasal vaccine vector in cattle administrated either alone or sequentially with non-human adenovirus-based vectors.

Adenoviruses, Human↗