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Biomedical subjects

D C Johnson

Publications and source records attributed to D C Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Comparison of the sensitivity of the caudal fold skin test and a commercial gamma-interferon assay for diagnosis of bovine tuberculosis.

A study to determine and compare the sensitivity of the caudal fold tuberculin test (CFT) and a commercial gamma-interferon (gamma-IFN) assay for diagnosis of bovine tuberculosis was conducted. A dairy herd with approximately a third of the cattle infected with Mycobacterium bovis was chosen for this study. All cattle from this herd were slaughtered, and tissue specimens for bacteriologic culturing and histologic examination were collected. Results of the CFT and gamma-IFN assay were compared with results of bacteriologic culturing and histologic examination to determine test sensitivity. Results were analyzed, using each of the following 4 standards to classify cattle as infected: positive test result by bacteriologic culturing only; histologic examination only; bacteriologic culturing and histologic examination; and bacteriologic culturing or histologic examination. Sensitivity of the CFT ranged from 80.4 to 84.4%, depending on the standard of comparison. Sensitivity of the gamma-IFN assay ranged from 55.4 to 97.1%, depending on the standard of comparison and on the method of interpretation. The CFT was significantly (P < 0.001) more sensitive than the gamma-IFN assay for diagnosis of bovine tuberculosis when the gamma-IFN assay was conducted and interpreted as instructed by the manufacturer. Maximum overall sensitivity was achieved when results of the CFT and gamma-IFN assay were interpreted in parallel.

Animals↗
PubMed1994

Herpes simplex virus glycoprotein D acquires mannose 6-phosphate residues and binds to mannose 6-phosphate receptors.

Herpes simplex viruses (HSV) use multiple and sequential receptors to enter host cells. HSV glycoprotein D (gD) has been implicated in binding to cellular receptors that facilitate virus penetration into cells. We used soluble forms of gD that were expressed in Chinese hamster ovary cells to characterize and identify a putative cellular receptor for HSV as the 275-kDa mannose 6-phosphate/insulin-like growth factor II receptor. Soluble gD also bound to the 46-kDa cation-dependent mannose 6-phosphate (Man-6-P) receptor and was extensively modified with Man-6-P residues on its Asn-linked oligosaccharides. Additionally, soluble gD was a high affinity substrate for N-acetylglucosamine-1-phosphotransferase, the first enzyme in the biosynthetic pathway for the addition of Man-6-P residues to lysosomal enzymes. The membrane form of gD immunoprecipitated from HSV-infected cells also bound to the 275-kDa mannose 6-phosphate/insulin-like growth factor II receptor, albeit poorly, and only a small fraction of the membrane gD was modified with Man-6-P. Notwithstanding this low level of mannose phosphorylation, the interaction between gD and Man-6-P receptors may play a role in some aspect of virus entry or egress.

Amino Acid Sequence↗
PubMed1994

A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes.

Herpes simplex virus (HSV) infection of human fibroblasts rapidly renders the cells resistant to lysis by HSV-specific CD8+ cytotoxic T lymphocytes (CTLs), which normally recognize cell surface major histocompatibility complex (MHC) class I proteins presenting viral peptides. Within 3 hr of infection with HSV, MHC class I protein complexes are retained in the endoplasmic reticulum (ER)/cis Golgi and show properties of complexes lacking antigenic peptide. The HSV immediate-early protein ICP47 is both necessary and sufficient to block transport of class I proteins and to inhibit lysis by CD8+ CTLs. The target for ICP47 is not known, but since ICP47 does not associate with membranes, it appears that ICP47 inhibits the production or stabilization of antigenic peptides or their translocation into the ER/cis Golgi. Thus, by expressing ICP47, HSV can evade detection by CD8+ T lymphocytes, perhaps explaining the predominance of CD4+ rather than CD8+ HSV-specific CTLs in vivo.

Amino Acid Sequence↗
PubMed1994

Viability of the neonatal rat isolated brainstem preparation by 31P MRS.

The isolated brainstem-spinal axis from the neonatal rat is an established model for studying neuronal responses of the ventilatory control system, however, its viability has not been clearly established. We studied the brainstem-spinal axis from newborn rats at 8.5 T with 31P NMR spectroscopy. The relative pattern of high energy phosphates (HEPs) was similar to that reported for the in vivo neonatal brain. The average pHi was 0.2 to 0.4 units less than the pHi for the in vivo neonatal brain. The HEPs and pHi were stable for 6 h, suggesting extended in vitro viability.

Adenosine Triphosphate↗
PubMed1994

Electrophysiologic and histologic effects of dissection of the connections between the atrium and posterior part of the atrioventricular node.

OBJECTIVES: This study was designed to examine the effects of destroying the posterior approaches to the atrioventricular (AV) node. BACKGROUND: Surgical and catheter ablation procedures have been developed for the cure of AV junctional reentrant tachycardia. Some of these destroy the posterior approaches to the AV node. METHODS: Atrioventricular node function and electrical excitation of Koch's triangle and the proximal coronary sinus were examined in 18 dogs. Dissection of the posterior atrionodal connections was performed in 10 dogs and a sham procedure in 8. After 28 to 35 days, repeat electrophysiologic and mapping studies were performed to assess changes in AV node function and the routes of AV and ventriculoatrial (VA) conduction. The AV junction was then examined with light microscopy. RESULTS: The compact AV node was undamaged in eight cases (80%). In two cases minor fibrosis occurred at the posterior limit of the compact node. The right-sided posterior atrionodal connections lying between the coronary sinus orifice and the tricuspid annulus were replaced by scar tissue in all cases, but the left-sided posterior connections and the anterior connections remained intact. Atrioventricular and VA conduction intervals and refractory periods were not altered. Atrioventricular junctional echoes were present in 10 dogs before and in 7 dogs after dissection (p = 0.06). Posterior (slow pathway) retrograde exists from the AV node were present in seven dogs before and in seven dogs after dissection. However, retrograde atrial excitation was altered in four of these seven dogs, so that the site of exit from the AV node was more leftward than it had been preoperatively. The node remained responsive to autonomic blocking drugs postoperatively. Double atrial electrograms similar to slow pathway potentials were found in all dogs. CONCLUSIONS: This procedure ablates the posterior atrionodal connections but rarely damages the compact AV node. Atrioventricular node function is not impaired and the node is not denervated. The mechanism of cure of AV junctional reentrant tachycardia is probably damage to the perinodal atrium. This suggests that part of the slow AV node pathway may lie outside the compact AV node. Dual AV node exits and double atrial electrograms are present in the normal canine heart.

Animals↗
PubMed1994

Simultaneous 60-electrode mapping of ventricular tachycardia using percutaneous catheters.

OBJECTIVES: We developed a new approach for mapping ventricular tachycardia at electrophysiologic study using simultaneous recordings from up to 60 catheter electrodes. BACKGROUND: Good results for surgical or catheter ablation of ventricular tachycardia are limited by the ability to detect and completely map all of the underlying arrhythmogenic areas. Currently, catheter mapping of all configurations of ventricular tachycardia is impossible or unsatisfactory in at least 60% of patients because of poorly tolerated rapid rates, nonsustained ventricular tachycardia or multiple configurations. METHODS: Twenty-four patients with recurrent ventricular tachycardia refractory to antiarrhythmic drugs were studied using up to six percutaneous decapolar catheters introduced into the ventricles. Left ventricular maps of ventricular tachycardia were achieved by two to three transseptal catheters, two to three transaortic catheters, a coronary sinus catheter and right ventricular catheters. Simultaneous endocardial maps of either right or left ventricles were possible with a resolution of approximately 1 to 2 cm. Up to 60 electrograms were digitized and recorded simultaneously using a custom-computerized mapping system. RESULTS: Successful maps of 73 ventricular tachycardia configurations were obtained in 22 patients. The mapping procedure failed in two patients because of inability to catheterize the left ventricle in one and inability to induce monomorphic ventricular tachycardia in the other. The mean (+/- SD) ventricular tachycardia cycle length was 285 +/- 53 ms (range 215 to 470). A total of 39 separate arrhythmogenic areas (median 1, interquartile [25% to 75%] range 1 to 3/patient) were detected, of which 21 (54%) were in the left ventricular free wall, 17 (44%) were in the ventricular septum, and 1 (2%) was in the right ventricular outflow tract. Ten patients (45%) had at least two arrhythmogenic areas. Thirteen patients subsequently underwent operation. All but one of the arrhythmogenic areas found at surgical mapping had been identified at preoperative catheter mapping. Complications of the preoperative mapping procedure occurred in four patients, with complete resolution in three and minor long-term sequelae in the other. CONCLUSIONS: This technique permits detailed catheter mapping of all types of monomorphic ventricular tachycardias, including those leading to hemodynamic collapse, and should enable better choice and direction of surgical or catheter ablation.

Adult↗
PubMed1994

Surgical procedure for the cure of atrioventricular junctional ("AV node") reentrant tachycardia: anatomic and electrophysiologic effects of dissection of the anterior atrionodal connections in a canine model.

OBJECTIVES: This study was undertaken to examine the electrophysiologic and anatomic effects of a surgical procedure that cures the anterior (common) type of atrioventricular (AV) junctional reentrant tachycardia. BACKGROUND: The procedure was designed to interrupt the reentrant circuit at the point of earliest atrial activation during AV junctional reentrant tachycardia, the anterior atrionodal connections. METHODS: Atrioventricular node function and the sequence of electrical excitation of Koch's triangle were examined in 18 dogs. Excitation of Koch's triangle was mapped using a 60-channel mapping system. Surgical dissection was performed in 10 dogs and a sham procedure in 8. After 28 to 35 days, AV node function and the atrial excitation pattern were reassessed. The AV junction was examined using light microscopy. RESULTS: Some degree of AV node damage was visible in all dogs in the dissection group, but it was minor in 40% of cases. The anterior part of the AV node was disconnected from the anterior atrionodal connections in all cases. Anterograde AV node function was mildly impaired. The median AH interval was increased (62 vs. 76 ms [interquartile ranges 48 to 72 and 64 to 104, respectively], p = 0.05), and the AV Wenckebach cycle length was increased (210 vs. 245 ms [interquartile ranges 200 to 230 and 210 to 260, respectively], p = 0.02). The degree of impairment of conduction was directly proportional to the length of dissection (p < 0.05) but not to the degree of damage to the AV node. Ventriculoatrial (VA) conduction was destroyed in 50% of dogs undergoing dissection but in none of those with a sham operation (p < 0.04). The AV node remained responsive to autonomic blocking drugs, and atrial mapping during ventricular pacing revealed that the site of exit from the AV node had been altered. CONCLUSIONS: The atrionodal connections closest to the His bundle are the preferred route of conduction through the AV node during normal AV or VA conduction. Destruction of these connections modifies AV node conduction. The surgical procedure selectively interrupts these connections, and this interruption is likely to be the mechanism of cure.

Animals↗
PubMed1994

Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells.

Herpes simplex virus (HSV) glycoproteins E and I (gE and gI) can act as a receptor for the Fc domain of immunoglobulin G (IgG). To examine the role of HSV IgG Fc receptor in viral pathogenesis, rabbits and mice were infected by the corneal route with HSV gE- or gI- mutants. Wild-type HSV-1 produced large dendritic lesions in the corneal epithelium and subsequent stromal disease leading to viral encephalitis, whereas gE- and gI- mutant viruses produced microscopic punctate or small dendritic lesions in the epithelium and no corneal disease or encephalitis. These differences were not related to the ability of the gE-gI oligomer to bind IgG because the differences were observed before the appearance of anti-HSV IgG and in mice, in which IgG binds to the Fc receptor poorly or not at all. Mutant viruses produced small plaques on monolayers of normal human fibroblasts and epithelial cells. Replication of gE- and gI- mutant viruses in human fibroblasts were normal, and the rates of entry of mutant and wild-type viruses into fibroblasts were similar; however, spread of gE- and gI- mutant viruses from cell to cell was significantly slower than that of wild-type HSV-1. In experiments in which fibroblast monolayers were infected with low multiplicities of virus and multiple rounds of infection occurred, the presence of neutralizing antibodies in the culture medium caused the yields of mutant viruses to drop dramatically, whereas there was a lesser effect on the production of wild-type HSV. It appears that cell-to-cell transmission of wild-type HSV-1 occurs by at least two mechanisms: (i) release of virus from cells and entry of extracellular virus into a neighboring cell and (ii) transfer of virus across cell junctions in a manner resistant to neutralizing antibodies. Our results suggest that gE- and gI- mutants are defective in the latter mechanism of spread, suggesting the possibility that the gE-gI complex facilitates virus transfer across cell junctions, a mode of spread which may predominate in some tissues. It is ironic that the gE-gI complex, usually considered an IgG Fc receptor, may, through its ability to mediate cell-to-cell spread, actually protect HSV from IgG in a manner different than previously thought.

Animals↗
PubMed1994

1H-NMR measurement of fractional dissociation of imidazole in intact animals.

The alphastat hypothesis states that intracellular acid-base status is regulated to maintain constancy of the fractional dissociation of intracellular protein and enzyme imidazole-histidine (alpha-imidazole). A major drawback of this theory has been the lack of a means to directly measure alpha-imidazole in intact animals. We developed a method for directly measuring alpha-imidazole in intact unanesthetized animals using 1H-nuclear magnetic resonance spectroscopy (NMR). We measured carnosine alpha-imidazole of white skeletal muscle from intact unanesthetized newts at three body temperatures (10, 20, and 30 degrees C). alpha-Imidazole remained constant, approximately 0.56, with alterations in body temperature, whereas intracellular pH (pHi) changed significantly (-0.015 U/degrees C), affirming the validity of the imidazole alphastat hypothesis for this tissue. This method was also used to determine the pK values of the imidazole moiety of carnosine and the imidazole moiety alone over a temperature (T) range 4-40 degrees C. The pK values of carnosine differed from those of imidazole, but the delta pK/delta T was the same. pHi was also determined using 31P-NMR and found to be the same as that calculated from carnosine alpha-imidazole values. Therefore Pi and carnosine share a similar pHi environment. We describe a novel technique to directly measure alpha-imidazole in intact tissue.

Animals↗
PubMed1994

Central control of ventilation in neuromuscular disease.

Neuromuscular diseases cause many changes that affect ventilation and ventilatory control. The pattern of ventilation may become abnormal because of muscle disease. Muscle fatigue and discordant breathing can lead to hypoventilation and CO2 retention. Motoneuron destructive and demyelinating disorders inevitably lead to hypoventilation and hypercapnia. Changes in chest wall mechanics can lead to changes in level of ventilation and ventilatory drive. In many neuromuscular disorders, ventilatory response to CO2 is depressed, but this does not imply an abnormal central control mechanism in all instances. Many patients with neuromuscular diseases have a normal ventilatory drive as manifested by a normal P0.1 but have low ventilation because of abnormalities in muscle function and neuromuscular transmission. Central drive is diminished in some patients with neuromuscular disease but not in the majority of cases. Hypoventilation during sleep is a common problem in neuromuscular diseases. Thus, a combination of factors can lead to abnormal patterns of breathing and hypoventilation in these disorders; no single pathophysiologic mechanism can explain all the abnormalities. Clinically, it is important to appreciate the prevalence of ventilatory control disorders and include appropriate evaluations when assessing patients with neuromuscular diseases and offering therapeutic options.

Chemoreceptor Cells↗
PubMed1994

Contribution of tumor necrosis factor-alpha and glucocorticoid in hydrazine sulfate-mediated protection against endotoxin lethality.

Hydrazine sulfate pretreatment has previously been shown in our laboratory to protect normal mice against endotoxin and D-galactosamine-sensitized mice against both exogenous tumor necrosis factor (TNF) and endotoxin. An intact pituitary is required for manifestation of the protective effects. Further, we have demonstrated that hydrazine sulfate pretreatment specifically modulates the TNF response to lipopolysaccharide (LPS) in mouse macrophages in vitro. This in vivo study was performed to test whether a reduced TNF response and/or increased glucocorticoid response may contribute to hydrazine sulfate protection against LPS-induced lethality in vivo. The results presented here establish that hydrazine sulfate pretreatment selectively attenuates circulating TNF levels following LPS challenge. Moreover, adrenalectomy abrogates hydrazine sulfate protection but does not prevent hydrazine sulfate attenuation of circulating TNF levels in response to LPS. Hydrazine sulfate-mediated protection is, however, restored permissively by corticosterone. Thus, the mechanism by which hydrazine sulfate protects against LPS lethality in adrenalectomized mice includes TNF modulation in response to endotoxin, as well as a pivotal requirement for glucocorticoid.

Adrenalectomy↗
PubMed1993

Epitope specificity of H-2Kb-restricted, HSV-1-, and HSV-2-cross-reactive cytotoxic T lymphocyte clones.

HSV-1-specific and HSV-1/HSV-2-cross-reactive H-2Kb-restricted cytotoxic T lymphocyte (CTL) clones were derived from a pool of splenic memory CTL (CTLm) obtained from HSV-1-infected C57BL/6 mice. Two of the HSV-1/HSV-2-cross-reactive CTL clones recognized HSV gB since H-2b cells infected with a recombinant adenovirus vector expressing HSV glycoprotein B (gB) provided a target for these CTL clones. The CTL recognition epitope was precisely defined as HSV-1 gB residues 498-505 using synthetic peptides and conforms to a predicted H-2Kb-binding motif. Immunization of C57BL/6 mice with the free synthetic peptide corresponding to this predicted minimal epitope (HSV-1 gB498-505) resulted in the generation of HSV-gB epitope-specific CD8+ CTL in the popliteal lymph nodes. The peptide-induced CTL recognize and lyse HSV-1 infected H-2b cells or cells pulsed with the synthetic peptide, gB498-505. The availability of CTL clones directed to this predicted minimal HSV CTL epitope should be helpful in understanding processing of HSV glycoprotein B and presentation of this CTL recognition epitope.

Amino Acid Sequence↗
PubMed1993

Herpes simplex virus (HSV) glycoproteins B and K inhibit cell fusion induced by HSV syncytial mutants.

Herpes simplex virus type 1 (HSV-1) glycoproteins K and B (gK and gB) are intimately involved in virus-induced fusion of cells. Certain mutations in the UL27 (gB) and UL53 (gK) genes confer a syncytial (syn) phenotype characterized by extensive fusion of infected cells and giving rise to multinucleated cells. We have used HSV-1 syn mutants in conjunction with transfected cells or adenovirus vectors to overexpress wild-type gK or gB, in order to study the role of these proteins in virus-induced membrane fusion. Transient expression of wild-type gK inhibited fusion induced by HSV-1 encoding a mutant form of gK (syn gK) but not by viruses encoding a mutant form of gB (syn gB). Stably transformed cells expressing relatively high levels of gK suppressed cell fusion induced by HSV-1 mutants with lesions in the gK gene but not an HSV-1 with a syn mutation in the gB gene. In addition, there were marked reductions in the plaquing efficiencies and yields of HSV-1 on these cell lines. Cell fusion caused by HSV-1 syn20, a mutant encoding syn gK, was suppressed when cells were coinfected with an Ad vector, AdgK, which expresses wild-type gK. AdgK did not suppress fusion induced by HSV-1 KTTS.1, which expresses syn gB. Conversely, cells coinfected with AdgB, an Ad vector expressing a wild-type form of gB and HSV-1 KTTS.1 (syn gB) were not fused, whereas cells coinfected with AdgB and HSV-1 syn20 (syn gK) were fused. Expression of a number of other HSV-1 glycoproteins using Ad vectors did not reduce membrane fusion induced by syn gK or syn gB. Together, these results support models in which gK and gB participate directly in the fusion of HSV-infected cells. Mutant forms of gB and gK apparently disregulate the fusion process, whereas wild-type forms of gB and gK can act to suppress membrane fusion induced by their mutant counterparts.

Adenoviridae↗
PubMed1993

Contrasting action of antiestrogen (ICI-182780) for preventing initiation of embryo implantation by estradiol or epidermal growth factor (EGF).

The pure estrogen antagonist ICI-182780, at doses above 50 micrograms/kg, effectively inhibited the initiation of embryo implantation in rats when administered on day 4 of pregnancy (day 1 = sperm positive). The same dose inhibited the implantation initiating effect of intravenous 25 ng of estradiol-17 beta in delayed implanting progesterone-primed hypophysectomized rats. In contrast, the anti-estrogen at a dose of 1 mg/kg was ineffective at inhibiting the initiation of implantation induced by intrauterine plus intravenous administration of murine epidermal growth factor to delayed implanting rats. The growth factor also initiated implantation of blastocysts transferred from donor animals injected with the anti-estrogen to progesterone-primed hypophysectomized recipients. The results clearly demonstrate that the implantation initiating effect of the growth factor is not inhibited by a pure estrogen antagonist, and therefore this estrogenic function does not appear to require action initiated by the classical estrogen receptor.

Animals↗
PubMed1993

Monitoring foreign gene expression by a human adenovirus-based vector using the firefly luciferase gene as a reporter.

We have constructed a helper-independent adenovirus type 5-luciferase recombinant (Ad5-Luc 3) containing the firefly luciferase gene flanked by simian virus 40 (SV40) regulatory sequences inserted in the early region 3 (E3) of the Ad5 genome. Expression of luciferase in cells infected with Ad5-Luc3 was relatively efficient. In HeLa cells approximately 20 micrograms luciferase per 10(6) cells was made by 36 h post-infection and a 62 kilo-Dalton (kDa) luciferase band was clearly visible in a [35S]methionine-labeled Ad5-Luc 3-infected cell extract analyzed directly by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The results of experiments in which cultured cells were infected with Ad5-Luc 3 in the presence or absence of 1-beta-D-arabinofuranosyl cytosine (AraC) showed that the majority of luciferase expression was dependent on viral DNA replication. This suggested that the enzyme was probably translated primarily from mRNA derived from transcripts expressed from the major late promoter of Ad5. An anti-luciferase antibody was raised in a rabbit and used to further characterize the luciferase expressed in HeLa cells infected with Ad5-Luc 3 by immunoprecipitations and Western blot analyses. The half-life of luciferase expressed in HeLa cells infected with Ad5-Luc 3 was calculated to be approximately 6-8 h by pulse chase analysis. Luciferase is likely to be a useful marker for monitoring virus dissemination and gene expression in experimental animals because assays for enzymatic activity are extremely sensitive and backgrounds are low in all tissues. In mice inoculated intraperitoneally (i.p.) with Ad5-Luc 3, luciferase activity was detected in the liver, spleen, kidney, and lung. A single i.p. inoculation of mice with Ad5-Luc 3 was sufficient to raise anti-luciferase antibody and Ad5 neutralizing antibody which persisted for at least 8 weeks. Even in the presence of circulating anti-luciferase and Ad5 neutralizing antibodies, luciferase activity could be detected in the livers, spleens, and kidneys of mice inoculated i.p. a second time with Ad5-Luc 3.

Adenoviridae Infections↗
PubMed1993

Immunogenicity in mice of tandem repeats of an epitope from herpes simplex gD protein when expressed by recombinant adenovirus vectors.

The antigenic and immunogenic potential was examined of human adenovirus type 5 (Ad) recombinants carrying and expressing from one to four tandem repeats of a linear neutralizing epitope from the gD protein of herpes simplex virus type 1 (HSV-1) as a fusion with the beta-galactosidase protein. The fusion proteins produced by these Ad vectors in infected cell culture reacted with a herpes simplex virus (HSV) epitope-specific monoclonal antibody to a degree dependent on the number of epitope repeats in the protein. Mice immunized by intraperitoneal injection of the Ad vectors developed an anti-HSV immune response as measured by ELISA and by HSV-1 neutralization assays. The mean antibody titre induced by a single injection of the Ad vector increased with the number of epitope repeats expressed by the recombinant. Any animal that had developed a serum-neutralizing titre of at least 1:80 survived challenge with a normally lethal dose of HSV-2 administered by the intraperitoneal route. Recombinant vectors expressing four repeats of the HSV epitope were as effective in antibody induction and protection as an adenovirus vector carrying and expressing the entire HSV gD protein. These results suggest that the expression of tandem repeats of appropriate epitopic sequences by adenovirus vectors may provide a safe and effective method of immunizing against HSV infection.

Adenoviruses, Human↗
PubMed1993

Mucosal immunity and protection after intranasal immunization with recombinant adenovirus expressing herpes simplex virus glycoprotein B.

A recombinant adenovirus (Ad) expressing glycoprotein B (gB) of herpes simplex virus (HSV) type 1 (AdgB8) was evaluated as a mucosal vaccine candidate. When administered intranasally (inl) to C57B1/6 mice, AdgB8 induced levels of serum anti-HSV gB IgG antibodies similar to those of mice immunized intraperitoneally (ip), which neutralized both HSV-1 and -2. Mice immunized inl with AdgB8 produced secretory IgA specific for HSV gB, but mice immunized ip did not. Splenic anti-HSV cytotoxic T lymphocytes (CTL) were observed after inl and ip immunization; however, there was a time-dependent decrease in the anti-HSV CTL activity from spleens of inl immunized mice. Anti-HSV CTL were also present in the mediastinal lymph nodes after inl but not ip AdgB8 immunization. Furthermore, mice immunized inl with AdgB8 were protected against heterologous inl challenge with HSV-2, and this protection lasted longer than in ip-immunized mice. These results indicate that mucosal immunization with a recombinant adenovirus can induce mucosal and systemic immune responses and provide long-term protection from mucosally or sexually transmitted viruses.

Administration, Intranasal↗