Persistence at one year of age of antigen-induced cellular immune responses in preterm infants vaccinated against whooping cough: comparison of three different vaccines and effect of a booster dose.

Due to their high risk of developing severe Bordetella pertussis (Bp) infections, it is recommended to immunize preterm infants at their chronological age. However, little is known about the persistence of their specific immune responses, especially of the cellular responses recognized to play a role in protection. We compared here the cellular immune responses to two major antigens of Bp between three groups of one year-old children born prematurely, who received for their primary vaccination respectively the whole cell vaccine Tetracoq(®) (TC), the acellular vaccine Tetravac(®) (TV), or the acellular vaccine Infanrix-hexa(®) (IR). Whereas most children had still detectable IFN-γ responses at one year of age, they were lower in the IR-vaccinated children compared to the two other groups. In contrast, both the TV- and the IR-vaccinated children displayed higher Th2-type immune responses, resulting in higher antigen-specific IFN-γ/IL-5 ratios in TC- than in TV- or IR-vaccinated children. The IFN-γ/IL-5 ratio of mitogen-induced cytokines was also lower in IR- compared to TC- or TV-vaccinated children. No major differences in the immune responses were noted after the booster compared to the pre-booster responses for each vaccine. The IR-vaccinated children had a persistently low specific Th1-type immune response associated with high specific Th2-type immune responses, resulting in lower antigen-specific IFN-γ/IL-5 ratios compared to the two other groups. We conclude that antigen-specific cellular immune responses persisted in one year-old children born prematurely and vaccinated during infancy at their chronological age, that a booster dose did not significantly boost the cellular immune responses, and that the Th1/Th2 balance of the immune responses is modulated by the different vaccines.

Humoral and B-cell memory responses in children five years after pertussis acellular vaccine priming.

The resurgence of pertussis suggests the need for greater efforts in understanding the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of humoral and B-cell memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac(®) vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa(®) (Infanrix) (GlaxoSmithKline Biologicals). We evaluated the specific immune responses in the two groups of children, 5 years after primary vaccination by measuring the persistence of IgG and antibody secreting cells (ASC) specific for vaccine antigens. Part of the enrolled children received only primary vaccination, while others had the pre-school boost dose. A similar level of antigen-specific IgG and ASC was found in Infanrix and Hexavac vaccinated children. The mean IgG levels were significantly higher in children that received the pre-school boost as compared with children that did not receive the boost dose. A longer persistence after the pre-school boost of IgG-Pertussis Toxin (PT) and IgG-pertactin levels was observed in Infanrix primed children, but it was not statistically significant. More than 80% of children presented a positive ASC B memory response. Around 50% of children still presented protective IgG-PT levels which are reduced to 36% in no-boosted children. The pre-school booster dose restores the percentage of protected children above 50%. In conclusion our data underline the importance of giving a booster dose 5 years after primary vaccination and suggest the need for a new vaccine able to induce a long lasting protective response.

Interactions spatiales et auto-organisation des végétations semi-arides

Les recherches récapitulées dans cette thèse de doctorat ont porté sur les causes de l’organisation spatiale des végétations périodiques. Ces structures paysagères aux motifs réguliers, tachetés, tigrés ou labyrinthiques, d’échelle décamétrique à hectométrique, couvrant des étendues considérables sur au moins trois continents, constituent un cas d’école dans l’étude des processus endogènes présidant à l’hétérogénéité du couvert végétal. Ces structures prennent place sur un substrat homogène, mis à part la rétroaction du couvert lui-même, et sont marquées par des écotones abrupts et la persistance d’une proportion considérable de sol nu. Plusieurs modèles ont mis en avant l’existence possible d’un phénomène d’auto-organisation du couvert, qui verrait une structure d’ensemble émerger des interactions locales entre individus. Ces modèles se basent sur le jeu simultané de la consommation de la ressource (compétition) et de l’amélioration de l’un ou l’autre des éléments du bilan de la même ressource par le couvert (facilitation). La condition à l’existence d’une structure d’ensemble spatialement périodique et stable réside dans une différence entre la portée de la compétition (plus grande) et celle de la facilitation. L’apparition de ces structures est modulée par le taux de croissance biologique, qui est le reflet des contraintes extérieures telles que l’aridité, le pâturage ou la coupe de bois. Le modus operandi des interactions spatiales supposées entre individus reste largement à préciser.

Nos recherches ont été menées au sud-ouest de la République du Niger, à l’intérieur et dans les environs du parc Régional du W. Trois axes ont été explorés :(i) Une étude de la dépendance spatiale entre la structure de la végétation (biovolumes cartographiés) et les paramètres du milieu abiotique (relief, sol), sur base d’analyses spectrales et cross-spectrales par transformée de Fourier (1D et 2D). (ii) Une étude diachronique (1956, 1975 et 1996) à large échelle (3000 km²) de l’influence de l’aridité et des pressions d’origine anthropique sur l’auto-organisation des végétations périodiques, basée sur la caractérisation de la structure spatiale des paysages sur photos aériennes via la transformée de Fourier en 2D. (iii) Trois études portant sur les interactions spatiales entre individus :En premier lieu, via l’excavation des systèmes racinaires (air pulsé) ;Ensuite, par un suivi spatio-temporel du bilan hydrique du sol (blocs de gypse) ;Enfin, via le marquage de la ressource par du deutérium.

Nous avons ainsi pu établir que les végétations périodiques constituent bien un mode d’auto-organisation pouvant survenir sur substrat homogène et modulé par les contraintes climatiques et anthropiques. Un ajustement rapide entre l’organisation des végétations périodiques et le climat a pu être montrée en zone protégée. La superficie et l’organisation des végétations périodiques y ont tour à tour progressé et régressé en fonction d’épisodes secs ou humides. Par contre, en dehors de l’aire protégée, la possibilité d’une restauration du couvert semble fortement liée au taux d’exploitation des ressources végétales. Ces résultats ont d’importantes implications quant à la compréhension des interactions entre climat et écosystèmes et à l’évaluation de leurs capacités de charge. La caractérisation de la structure spatiale des végétations arides, notamment par la transformée de Fourier d’images HR, devrait être généralisée comme outil de monitoring de l’état de ces écosystèmes. Nos études portant sur les modes d’interactions spatiales ont permis de confirmer l’existence d’une facilitation à courte portée du couvert végétal sur la ressource. Cependant, cette facilitation ne semble pas s’exercer sur le terme du bilan hydrique traditionnellement avancé, à savoir l’infiltration, mais plutôt sur le taux d’évaporation (deux fois moindre à l’ombre des canopées). Ce mécanisme exclut l’existence de transferts diffusifs souterrains entre sols nu et fourrés. Des transferts inverses semblent d’ailleurs montrés par le marquage isotopique. L’étude du bilan hydrique et la cartographie du micro-relief, ainsi que la profondeur fortement réduite de la zone d’exploitation racinaire, jettent de sérieux doutes quant au rôle communément admis des transferts d’eau par ruissellement/diffusion de surface en tant que processus clé dans la compétition à distance entre les plantes. L’alternative réside dans l’existence d’une compétition racinaire de portée supérieure aux canopées. Cette hypothèse trouve une confirmation tant par les rhizosphères excavées, superficielles et étendues, que dans le marquage isotopique, montrant des contaminations d’arbustes situés à plus de 15 m de la zone d’apport. De même, l’étude du bilan hydrique met en évidence les influences simultanées et contradictoires (facilitation/compétition) des ligneux sur l’évapotranspiration.

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This PhD thesis gathers results of a research dealing with the causes of the spatial organisation of periodic vegetations. These landscape structures, featuring regular spotted, labyrinthine or banded patterns of decametric to hectometric scale, and extending over considerable areas on at least three continents, constitute a perfect study case to approach endogenous processes leading to vegetation heterogeneities. These patterns occur over homogeneous substratum, except for vegetation’s own feedbacks, and are marked by sharp ecotones and the persistence of a considerable amount of bare soil. A number of models suggested a possible case of self-organized patterning, in which the general structure would emerge from local interactions between individuals. Those models rest on the interplay of competitive and facilitative effects, relating to soil water consumption and to soil water budget enhancement by vegetation. A general necessary condition for pattern formation to occur is that negative interactions (competition) have a larger range than positive interactions (facilitation). Moreover, all models agree with the idea that patterning occurs when vegetation growth decreases, for instance as a result of reduced water availability, domestic grazing or wood cutting, therefore viewing patterns as a self-organised response to environmental constraints. However the modus operandi of the spatial interactions between individual plants remains largely to be specified.

We carried out a field research in South-West Niger, within and around the W Regional Park. Three research lines were explored: (i) The study of the spatial dependency between the vegetation pattern (mapped biovolumes) and the factors of the abiotic environment (soil, relief), on the basis of spectral and cross-spectral analyses with Fourier transform (1D and 2D). (ii) A broad scale diachronic study (1956, 1975, 1996) of the influence of aridity and human induced pressures on the vegetation self-patterning, based on the characterisation of patterns on high resolution remote sensing data via 2D Fourier transform. (iii) Three different approaches of the spatial interactions between individuals: via root systems excavation with pulsed air; via the monitoring in space and time of the soil water budget (gypsum blocks method); and via water resource labelling with deuterated water.

We could establish that periodic vegetations are indeed the result of a self-organisation process, occurring in homogeneous substratum conditions and modulated by climate and human constraints. A rapid adjustment between vegetation patterning and climate could be observed in protected zones. The area and patterning of the periodic vegetations successively progressed and regressed, following drier or wetter climate conditions. On the other hand, outside protected areas, the restoration ability of vegetation appeared to depend on the degree of vegetation resource exploitation. These results have important implications regarding the study of vegetation-climate interactions and the evaluation of ecosystems’ carrying capacities. Spatial pattern characterisation in arid vegetations using Fourier transform of HR remote sensing data should be generalised for the monitoring of those ecosystems. Our studies dealing with spatial interaction mechanisms confirmed the existence of a short range facilitation of the cover on water resource. However, this facilitation does not seem to act through the commonly accepted infiltration component, but rather on the evaporative rate (twice less within thickets). This mechanism excludes underground diffusive transfers between bare ground and vegetation. Inverse transfers were even shown by deuterium labelling. Water budget study and micro-elevation mapping, along with consistent soil shallowness, together cast serious doubts on the traditional mechanism of run-off/diffusion of surface water as a key process of the long range competition between plants. An alternative explanation lies in long range root competition. This hypothesis find support as well in the excavated root systems, shallow and wide, as in isotopic labelling, showing contaminations of shrubs located up to 15 m of the irrigated area. Water budget study also evidenced simultaneous contradictory effects (facilitation/competition) of shrubs on evapotranspiration.