Biomedical subjects

Daniel Schmitt

Publications and source records attributed to Daniel Schmitt.

At least 19 recordsLinked to original sources

PubMed2006

Adaptive value of ambling gaits in primates and other mammals.

At speeds between the walk and the gallop, most mammals trot. Primates almost never trot, and it has been claimed that they transition directly from a walk to a gallop without any distinctive mid-speed running gait. If true, this would be another characteristic difference between the locomotion of primates and that of most other quadrupedal mammals. Presently, however, few data exist concerning the actual presence or absence of intermediate-speed gaits (i.e. gaits that are used between a walk and a gallop) in primates. Video records of running in twelve primate species reveal that, unlike most other mammals, all the primates studied almost exclusively adopt an 'amble'--an intermediate-speed running gait with no whole-body aerial phase--rather than trot. Ambling is also common in elephants and some horses, raising the question of why ambling is preferred over trotting in these diverse groups of animals. Mathematical analyses presented here show that ambling ensures continuous contact of the body with the substrate while dramatically reducing vertical oscillations of the center of mass. This may explain why ambling appears to be preferable to trotting for extremely large terrestrial mammals such as elephants and for arboreal mammals like primates that move on unstable branches. These findings allow us to better understand the mechanics of these unusual running gaits and shed new light on primate locomotor evolution.

Adaptation, Physiological↗

PubMed2005

Force plate for measuring the ground reaction forces in small animal locomotion.

The importance of kinetic force plate studies of locomotion in small animals has grown recently with the increasing use of rodent models for studies of musculoskeletal diseases. However, the force plates for use with animals much smaller than a cat are difficult to design and use. Here we present data on a commercially available small force plate that accurately collects whole-body and, in a modified form, single-limb ground reaction forces in mice. The method used here is convenient, inexpensive, and readily adaptable for use with a variety of small species.

Animals↗

PubMed2005

TNF-alpha enhances phenotypic and functional maturation of human epidermal Langerhans cells and induces IL-12 p40 and IP-10/CXCL-10 production.

Dendritic cells (DC) play a central role in immunity/tolerance decision, depending on their activation/maturation state. TNF-alpha is largely produced in the skin under inflammatory conditions. However, it still remains to be defined how TNF-alpha modulates the activation status of human LC, the most specialized DC controlling skin immunity. Here, we reported that fresh immature LC, highly purified from healthy human skin and exposed for two days to TNF-alpha under serum-free conditions, expressed up-regulated level of co-stimulatory molecules (CD40, CD54, CD86), maturation markers (CD83, DC-LAMP), CCR7 lymph node homing receptor, and down-regulated Langerin level, in a dose-dependent manner. This mature phenotype is closely associated with enhanced LC allostimulatory capacity. Furthermore, TNF-alpha significantly increased the number of viable LC and decreased their spontaneous apoptosis. More importantly, TNF-alpha induced LC to produce both IFN-gamma-inducible-protein IP-10/CXCL10, a Th1-attracting chemokine and IL-12 p40. Bioactive IL-12 p70 was never detected, even after additional CD40 stimulus. The results implicate LC as an effective target through which TNF-alpha may up- or down-regulate the inflammatory skin reactions.

Antigens, CD↗

PubMed2005

Role of the prehensile tail during ateline locomotion: experimental and osteological evidence.

The dynamic role of the prehensile tail of atelines during locomotion is poorly understood. While some have viewed the tail of Ateles simply as a safety mechanism, others have suggested that the prehensile tail plays an active role by adjusting pendulum length or controlling lateral sway during bimanual suspensory locomotion. This study examines the bony and muscular anatomy of the prehensile tail as well as the kinematics of tail use during tail-assisted brachiation in two primates, Ateles and Lagothrix. These two platyrrhines differ in anatomy and in the frequency and kinematics of suspensory locomotion. Lagothrix is stockier, has shorter forelimbs, and spends more time traveling quadrupedally and less time using bimanual suspensory locomotion than does Ateles. In addition, previous studies showed that Ateles exhibits greater hyperextension of the tail, uses its tail to grip only on alternate handholds, and has a larger abductor caudae medialis muscle compared to Lagothrix. In order to investigate the relationship between anatomy and behavior concerning the prehensile tail, osteological data and kinematic data were collected for Ateles fusciceps and Lagothrix lagothricha. The results demonstrate that Ateles has more numerous and smaller caudal elements, particularly in the proximal tail region. In addition, transverse processes are relatively wider, and sacro-caudal articulation is more acute in Ateles compared to Lagothrix. These differences reflect the larger abductor muscle mass and greater hyperextension in Ateles. In addition, Ateles shows fewer side-to-side movements during tail-assisted brachiation than does Lagothrix. These data support the notion that the prehensile tail represents a critical dynamic element in the tail-assisted brachiation of Ateles, and may be useful in developing inferences concerning behavior in fossil primates.

Animals↗

PubMed2005

UVA radiation impairs phenotypic and functional maturation of human dermal dendritic cells.

There is now strong evidence that the ultraviolet A (UVA) part of the solar spectrum contributes to the development of skin cancers. Its effect on the skin immune system, however, has not been fully investigated. Here, we analyzed the effects of UVA radiation on dermal dendritic cells (DDC), which, in addition, provided further characterization of these cells. Dermal sheets were obtained from normal human skin and irradiated, or not, with UVA at 2 or 12 J per cm2. After a 2 d incubation, the phenotype of emigrant cells was analyzed by double immunostaining and flow cytometry. Results showed that migratory DDC were best characterized by CD1c expression and that only few cells co-expressed the Langerhans cell marker Langerin. Whereas the DC extracted from the dermis displayed an immature phenotype, emigrant DDC showed increased expression of HLA-DR and acquired co-stimulation and maturation markers. We showed here that UVA significantly decreased the number of viable emigrant DDC, a process related to increased apoptosis. Furthermore, UVA irradiation impaired the phenotypic and functional maturation of migrating DDC into potent antigen-presenting cells, in a concentration-dependent manner. The results provide further evidence that UVA are immunosuppressive and suggest an additional mechanism by which solar radiation impairs immune response.

Apoptosis↗

PubMed2004

Mechanical energy and effective foot mass during impact loading of walking and running.

The human heel pad is considered an important structure for attenuation of the transient force caused by heel-strike. Although the mechanical properties of heel pads are relatively well understood, the mechanical energy (Etot) absorbed by the heel pad during the impact phase has never been documented directly because data on the effective foot mass (Meff) was previously unavailable during normal forward locomotion. In this study, we use the impulse-momentum method (IMM) for calculating Meff from moving subjects. Mass-spring-damper models were developed to evaluate errors and to examine the effects of pad property, upper body mass, and effective leg spring on Meff. We simultaneously collected ground reaction forces, pad deformation, and lower limb kinematics during impact phase of barefoot walking, running, and crouched walking. The latter was included to examine the effect of knee angle on Meff. The magnitude of Meff as a percentage of body mass (M(B)) varies with knee angle at impact and significantly differs among gaits: 6.3%M(B) in walking, 5.3%M(B) in running, and 3.7%M(B) in crouched walking. Our modeling results suggested that Meff is insensitive to heel pad resilience and effective leg stiffness. At the instant prior to heel strike, Etot ranges from 0.24 to 3.99 J. The combination of video and forceplate data used in this study allows analyses of Etot and Etot as a function of heel-strike kinematics during normal locomotion. Relationship between Meff and knee angle provides insights into how changes in posture moderate impact transients at different gaits.

Computer Simulation↗

PubMed2004

Migration and maturation of human dendritic cells infected with Toxoplasma gondii depend on parasite strain type.

Migration and maturation of human dendritic cells derived from CD34+ progenitor cells (DC) infected by Toxoplasma gondii were studied in an in vitro model. We demonstrated that infection with virulent type I strains RH and ENT or type II low virulent strains PRU and CAL induced DC migration towards MIP-3beta. However, type II strains induced a higher percentage of migrating cells than that induced by type I strains or positive controls (chemical allergen or lipopolysaccharides). Type II strains produced soluble factors responsible of the high migration whereas heat killed tachyzoites did not induced a migration higher than positive controls. We also demonstrated that infection by virulent strains and not by type II stains or heat killed tachyzoites triggers DC maturation. A soluble factor released by type II strains was responsible of the absence of DC maturation. Taken together, these results demonstrated that the interference of T. gondii in the behaviour of DC functions is related to the strain types and can be supported by secretion of soluble factors by the parasite.

Animals↗

PubMed2004

Subcellular compartmentalization of ceramide metabolism: MAM (mitochondria-associated membrane) and/or mitochondria?

Recent studies by our group and others have disclosed the presence of ceramides in mitochondria, and the activities of ceramide synthase and reverse ceramidase in mitochondria have also been reported. Since a possible contamination with the ER (endoplasmic reticulum)-related compartment MAM (mitochondria-associated membrane) could not be ruled out in previous studies, we have re-investigated the presence of the enzymes of ceramide metabolism in mitochondria and MAM highly purified from rat liver. In the present paper, we show that purified mitochondria as well as MAM are indeed able to generate ceramide in vitro through both ceramide synthase or reverse ceramidase, whereas the latter enzyme activity is barely detectable in microsomes. Moreover, ceramide synthase activities were recovered in outer mitochondrial membranes as well as in inner mitochondrial membranes. Using radiolabelled sphingosine as a substrate, mitochondria could generate ceramide and phytoceramide. However, the in vitro sensitivity of ceramide synthase toward FB1 (fumonisin B1) in mitochondria as well as in MAM was found to depend upon the sphingoid base: whereas dihydrosphingosine N-acyltransferase was inhibited by FB1 in a concentration-dependent manner, FB1 actually activated the ceramide synthase when using sphingosine as a substrate. Acylation of sphingosine 1-phosphate and dihydrosphingosine 1-phosphate, generating ceramide 1-phosphate, was also shown with both subcellular fractions. Moreover, the same difference in sensitivity towards FB1 for the ceramide synthase activities was seen between the two phosphorylated sphingoid bases, raising the possibility that distinct base-specific enzymes may be involved as ceramide synthases. Collectively, these results demonstrate the involvement of mitochondria in the metabolism of ceramides through different pathways, thereby supporting the hypothesis that topology of ceramide formation could determine its function.

Animals↗

PubMed2004

New technique for studying reaction forces during primate behaviors on vertical substrates.

Recording reaction forces from primates during behaviors on vertical substrates, such as leaping, climbing, or biting trees, typically requires the design and construction of customized recording devices or mounting commercially available force platforms in a vertical position. The technical difficulties imposed by either option have hindered in vivo research on the kinetics of primate behaviors on vertical substrates. We describe a simple, inexpensive apparatus for recording forces from primate behaviors on vertical substrates. The apparatus includes an instrumented beam fastened directly to a horizontal force platform and a surrounding vertical substrate that does not contact the instrumented beam or platform. The contact piece at the end of the instrumented beam is positioned flush with the noninstrumented vertical substrate, and reaction forces elicited on this instrumented section are directed to the force platform. Because most of the vertical substrate is not instrumented, we can isolate and record forces from a single limb or jaw during a behavior. Biewener and Full ([1992] Biomechanics Structures and Positions: A Practical Approach; New York: Oxford University press, p. 45-73) gave seven criteria to consider when designing a customized force-recording device. Where appropriate, we tested if our apparatus met their criteria. The apparatus accurately records forces in three orthogonal directions, has low cross-talk, maintains a high frequency response, exhibits a linear response up to at least 200 Newtons, and displays a uniform response to a given force across the instrumented contact piece. Our design does not easily facilitate the identification of the point of force application. Therefore, joint moments cannot be easily calculated. This limitation, however, does not affect the apparatus's ability to accurately record the magnitude and direction of a force (as shown by other tests). We developed this apparatus to measure jaw forces during tree gouging in common marmosets (Callithrix jacchus), but the general design can be readily modified to study a variety of primate behaviors on vertical substrates.

Animals↗

PubMed2004

Seasonal variation in body mass and locomotor kinetics of the fat-tailed dwarf lemur (Cheirogaleus medius).

The fat-tailed dwarf lemur (Cheirogaleus medius) is unusual among primates in storing large amounts of fat subcutaneously prior to hibernating during the winter months. In doing so, it increases its body mass by more than 50%, with a substantial weight gain in the tail. This seasonal increase in mass provides a unique natural experiment to examine how changes in body mass affect substrate reaction forces during locomotion. As body mass increases, it is expected that the limbs of the fat-tailed dwarf lemur will be subjected to greater peak vertical substrate reaction forces during quadrupedal walking. However, whether or not these peak substrate reaction forces will increase proportionally across forelimbs and hindlimbs as body mass increases is unknown. Substrate reaction forces were collected on four adult C. medius walking quadrupedally on a 28-mm pole attached to a force platform. Peak vertical substrate reaction forces (Vpk) (N) were analyzed and compared for a cross-sectional sample of different body masses (180-300 g). Forelimb and hindlimb Vpk were positively correlated with body mass, with hindlimb Vpk always higher than forelimb Vpk. However, the rate at which Vpk increased relative to body mass was higher for the hindlimb than the forelimb. This disproportion in weight distribution between the forelimbs and hindlimbs as body mass increases appears to be linked to the accumulation of fat in the tail. It is likely that storing fat in the tail region may shift the center of mass more caudally, from a more cranial position when the tail is thinner. Such a caudal shift of the center of mass-either morphological or dynamic-is believed to have played an important role in the functional differentiation of the limbs and the evolution of locomotor modes of several tetrapod groups, including dinosaurs and primates.

Adipose Tissue↗

PubMed2004

The paleobiology of Amphipithecidae, South Asian late Eocene primates.

Analysis of the teeth, orbital, and gnathic regions of the skull, and fragmentary postcranial bones provides evidence for reconstructing a behavioral profile of Amphipithecidae: Pondaungia, Amphipithecus, Myanmarpithecus (late middle Eocene, Myanmar) and Siamopithecus (late Eocene, Thailand). At 5-8 kg, Pondaungia, Amphipithecus, and Siamopithecus are perhaps the largest known Eocene primates. The dental and mandibular anatomy suggest that large-bodied amphipithecids were hard-object feeders. The shape of the mandibular corpus and stiffened symphysis suggest an ability to resist large internal loads during chewing and to recruit significant amounts of muscle forces from both the chewing and non-chewing sides of the jaw so as to increase bite force during mastication. The large spatulate upper central incisor of Pondaungia and projecting robust canines of all the larger amphipithecids suggest that incisal food preparation was important. The molars of Siamopithecus, Amphipithecus, and Pondaungia have weak shearing crests. This, and the thick molar enamel found in Pondaungia, suggests a diet of seeds and other hard objects low in fiber. In contrast, Myanmarpithecus was smaller, about 1-2 kg; its cheek teeth suggest a frugivorous diet and do not imply seed eating. Postcranial bones (humerus, ulna, and calcaneus) of a single large amphipithecid individual from Myanmar suggest an arboreal quadrupedal locomotor style like that of howler monkeys or lorises. The humeral head is rounded, proximally oriented, and the tuberosities are low indicating an extremely mobile glenohumeral joint. The great thickness of the midshaft cortical bone of the humerus implies enhanced ability to resist bending and torsion, as seen among slow moving primate quadrupeds. The elbow joint exhibits articular features for enhanced stability in habitually flexed positions, features also commonly found in slow moving arboreal quadrupeds. The short distal load arm of the calcaneus is consistent with, but not exclusive to, slow, arboreal quadrupedalism, and suggests no reliance on habitual leaping.

Animals↗

PubMed2004

Substrate alters forelimb to hindlimb peak force ratios in primates.

It is often claimed that the walking gaits of primates are unusual because, unlike most other mammals, primates appear to have higher vertical peak ground reaction forces on their hindlimbs than on their forelimbs. Many researchers have argued that this pattern of ground reaction force distribution is part of a general adaptation to arboreal locomotion. This argument is frequently used to support models of primate locomotor evolution. Unfortunately, little is known about the force distribution patterns of primates walking on arboreal supports, nor do we completely understand the mechanisms that regulate weight distribution in primates. We collected vertical peak force data for seven species of primates walking quadrupedally on instrumented terrestrial and arboreal supports. Our results show that, when walking on arboreal vs. terrestrial substrates, primates generally have lower vertical peak forces on both limbs but the difference is most extreme for the forelimb. We found that force reduction occurs primarily by decreasing forelimb and, to a lesser extent, hindlimb stiffness. As a result, on arboreal supports, primates experience significantly greater functional differentiation of the forelimb and hindlimb than on the ground. These data support long-standing theories that arboreal locomotion was a critical factor in the differentiation of the forelimbs and hindlimbs in primates. This change in functional role of the forelimb may have played a critical role in the origin of primates and facilitated the evolution of more specialized locomotor behaviors.

Animals↗

PubMed2004

When integrated in a subepithelial mucosal layer equivalent, dendritic cells keep their immature stage and their ability to replicate type R5 HIV type 1 strains in the absence of T cell subsets.

Many potential targets of human immunodeficiency virus type 1 (HIV-1) reside in the human reproductive tract, including dendritic cells (DC). The ability of these cells to replicate HIV-1 is dependent on many factors such as their differentiation/maturation stage. Nevertheless, precise mechanisms underlying the early steps of transmucosal infection are still unknown. Our purpose was to investigate DC/HIV-1 interactions in a subepithelial mucosal layer equivalent (SEMLE) reconstructed in vitro. We used mixed interstitial DC (IntDC)/Langerhans cell (LC)-like cell subpopulations generated in vitro from CD34(+) progenitors. These cells were either integrated in SEMLE or maintained in suspension. Experimental infections were performed with a type X4 strain (HIV-1(LAI)) and a type R5 strain (HIV-1(Ba-L)). Proviral DNA was detected by in situ polymerase chain reaction (PCR) and viral replication was quantified by measuring p24 core protein release in the culture media. Our results showed that SEMLE enable DC to retain immature stage and reproduce the tropic selection that occurs in vivo. Indeed, IntDC/LC were infected by both types of HIV-1 strains, regardless of the infection schedule, whereas only type R5 virus replicated in DC in the absence of T cell subsets. Furthermore, the ability of DC to replicate HIV-1(BaL) was lost after 14 days of culture unless the cells had previously been integrated in SEMLE. These results suggest that this 3D model maintains the ability of DC to replicate type R5 virus by delaying their maturation. In conclusion, this in vitro model mimics human submucosa and can be considered as relevant for studying the preliminary steps of transmucosal HIV-1 infection.

Antigens, CD34↗

PubMed2003

The inhibition of MAPK pathway is correlated with down-regulation of MMP-9 secretion induced by TNF-alpha in human keratinocytes.

MMP-9 (92 kDa) is the major gelatinase able to degrade collagen IV, secreted by keratinocytes that are actively involved in wound-healing or tumorigenesis. Since the invasive phenotype of cancers is dependent on MMP-9 expression, it appeared of interest to precisely characterize which signal transduction pathways activated by TNF-alpha are involved in MMP-9 up-regulation induced by TNF-alpha. In HaCaT cells, activation of MMP-9 occurs at the transcriptional level. Inhibition of the MAPK pathway using specific inhibitors of the Ras, Raf, MEK1/2, and Erk1/2 cascade was correlated with a marked inhibition of MMP-9 activity, as determined by gene and protein expression. MAPK pathway activation via TNF-alpha was confirmed by marked AP-1 activation detected in EMSA. Under our experimental conditions, p38 MAPK and SAPK/JNK pathways were not activated. Gene and protein expression of other MMPs that regulate MMP-9, such as MMP-1 and MMP-13, were also up-regulated by TNF-alpha and inhibited by UO126, providing evidence that the MAPK pathway plays a fundamental role in the regulation of MMP-9 secretion by keratinocytes. As TNF-alpha is known to be a main activator of NF-kappaB pathway, the effects of campthothecin and caffeic acid were investigated, such as, TNF-alpha campthothecin up-regulated MMP-9 activity but caffeic acid only weakly inhibited MMP-9 activation induced by TNF-alpha. However, NF-kappaB is activated as shown from immunostaining data, a nuclear staining and higher Western blotting expression of p50 and p65 NF-kappaB subunits were detected after TNF-alpha treatment. A higher specific signal was also detected in EMSA for TNF-alpha-treated cells.

Caffeic Acids↗

PubMed2003

Comparative effects of polyphenols from green tea (EGCG) and soybean (genistein) on VEGF and IL-8 release from normal human keratinocytes stimulated with the proinflammatory cytokine TNFalpha.

In skin inflammation, vascular endothelial growth factor (VEGF) and IL-8 play an important role and are produced by activated keratinocytes. Recently, some polyphenols have been reported to exhibit antiinflammatory and antiangiogenic properties. We therefore evaluated the effects of green tea, its major component epigallocatechin-3-gallate (EGCG) and an isoflavone derived from soybean (genistein) on the release of VEGF and IL-8 by activated normal human keratinocytes (NHK). NHK cultured in defined medium were stimulated for 48 h with the proinflammatory cytokine TNFalpha with the addition or not of different concentrations of polyphenols. Levels of VEGF and IL-8 were measured in cell supernatants by enzyme-linked immunosorbent assays. The different constituents tested inhibited keratinocyte proliferation without inducing apoptosis. They reduced in a dose-dependent manner the basal release and the upregulation of VEGF in NHK. Green tea and EGCG were also potent inhibitors of IL-8 release by TNFalpha-stimulated NHK, whereas genistein exerted only minor effects. These results underline the divergent pathways involved in the downregulation of VEGF and IL-8 by polyphenols in activated keratinocytes. They also suggest that polyphenols may contribute to moderate inflammatory processes in skin diseases associated with angiogenesis.

Angiogenesis Inhibitors↗

PubMed2003

New three-dimensional echocardiographic system using digital radiofrequency data--visualization and quantitative analysis of aortic valve dynamics with high resolution: methods, feasibility, and initial clinical experience.

BACKGROUND: Common 3D systems have only limited spatial and temporal resolution (frame rate of 25 Hz). Thin structures such as cardiac valves are not imaged exactly; rapid movement patterns cannot be precisely recorded. The objective of the present project was to achieve radiofrequency (RF) data transmission to the 3D workstation to improve image resolution. METHODS AND RESULTS: A commercially available echocardiographic system (5-MHz transesophageal echocardiography probe) with an integrated raw data interface enables transmission of RF data (up to 40 megabytes per second). A 3D data set may contain up to 3 gigabytes, so that all of the high-resolution ultrasound information of the 2D image is available. Frame rates of up to 168 Hz result in temporal resolution 6 times that of standard 3D systems. The applicability of the system and the image quality were tested in 10 patients. The structure of the aortic valve and the dynamic changes were depicted by volume rendering. The changes in the orifice areas were measured in frame-by-frame planimetry. The mean number of frames recorded per cardiac cycle was 122+/-16. The improved structural resolution enabled a detailed imaging of the morphology of the aortic cusps. The rapid systolic movement patterns were recorded with up to 51 frames. The high number of frames enabled creation of precise area-time diagrams. Thus, the individual phases of aortic valve movement (rapid opening, slow valve closing, and rapid valve closing) could be analyzed quantitatively. CONCLUSIONS: A 3D system based on RF data enables high-resolution imaging of cardiac movement patterns. This offers new perspectives for qualitative and quantitative analyses, especially of cardiac valves.

Aortic Valve↗

PubMed2003

The mitochondria-associated endoplasmic-reticulum subcompartment (MAM fraction) of rat liver contains highly active sphingolipid-specific glycosyltransferases.

Although most glycosphingolipids (GSLs) are thought to be located in the outer leaflet of the plasma membrane, recent evidence indicates that GSLs and their precursor, ceramide, are also associated with intracellular organelles and, particularly, mitochondria. GSL biosynthesis starts with the formation of ceramide in the endoplasmic reticulum (ER), which is transported by controversial mechanisms to the Golgi apparatus, where stepwise addition of monosaccharides on to ceramides takes place. We now report the presence of GSL-biosynthetic enzymes in a subcompartment of the ER previously characterized and termed 'mitochondria-associated membrane' (MAM). MAM is a membrane bridge between the ER and mitochondria that is involved in the biosynthesis and trafficking of phospholipids between the two organelles. Using exogenous acceptors coated on silica gel, we demonstrate the presence of ceramide glucosyltransferase (Cer-Glc-T), glucosylceramide galactosyltransferase and sialyltransferase (SAT) activities in the MAM. Estimation of the marker-enzyme activities showed that glycosyltransferase activities could not be ascribed to cross-contamination of MAM by Golgi membranes. Cer-Glc-T was found to have a marked preference for ceramide bearing phytosphingosine as sphingoid base. SAT activities in MAM led to the synthesis of G(M3) ganglioside and small amounts of G(D3). G(M1) was also synthesized along with G(M3) upon incubation of the fraction with exogenous unlabelled G(M3), underlying the presence of other sphingolipid-specific glycosyltransferases in MAM. On the basis of our results, we propose MAM as a privileged compartment in providing GSLs for mitochondria.

Animals↗

PubMed2003

Immunization onto shaved skin with a bacterial enterotoxin adjuvant protects mice against respiratory syncytial virus (RSV).

This study evaluated the potential of the skin as a non invasive route for RSV vaccination using two G protein-derived molecules, G2Na and G5 in mice. G2Na contains T and B-cell epitopes whether G5 is a pure B-cell epitope. In contrast to G5, G2Na coadministered with CT three times at 1 month interval onto 1cm of square area shaved skin, elicited a consistent serum anti-G2Na and anti-CT IgG response. The anti-G2Na IgG response was dominated by IgG1 isotype, an indirect marker of a Th2 type of response. Dramatic reduction and decrease of RSV titers in lung tissues and in the nasal tract, respectively, following intranasal virus challenge revealed biological relevance of the transcutaneous immunization in the context of RSV vaccine. These results suggest that the transcutaneous route may offer a promising potential for novel RSV vaccine strategy, simple, painless and economical.

Adjuvants, Immunologic↗