10 research outputs found

    Behavior of respiratory syncytial virus in piglet tracheal organ culture

    No full text
    Piglet tracheal organ cultures were infected with respiratory syncytial virus (RSV) and observed for 21 days. Light and immunofluorescence microscopy demonstrated destruction of the ciliated epithelial cells and the presence of viral antigens in the epithelium. Virus was shed in high titer for 12-19 days. Ciliostasis could be quanti-tated, and it was shown that several strains of RSV grew and damaged tracheal organ cultures in a similar fashion. A temperature-sensitive mutant of RSV, Is-I, was exam-ined at permissive (33 C) and restrictive (37 C) temperatures. This mutant, al-though somewhat attenuated at 37 C, was still found to cause damage to the ciliated epithelium and to replicate at both temperatures. This behavior is similar to that af-ter inoculation of Is-I into volunteers. This in vitro model may prove useful in the study of RSV disease and in the evaluation of candidate live virus vaccines. Respiratory syncytial virus (RSV) is the most important etiologic agent of lower respiratory tract disease in infancy [1]. Studies of human RSV using animal models have been of limite

    Interleukin 7 from maternal milk crosses the intestinal barrier and modulates T-cell development in offspring

    No full text
    Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue.PLoS ON

    The development of recombinant Adenoviral vaccines to target pneumovirus infection

    No full text
    Respiratory Syncytial Virus (RSV) is a member of the pneumovirus genus (family Paramyxoviridae, subfamily Pneumovirinae). RSV is an important respiratory virus of both infants and the elderly, representing an underappreciated burden on health care systems. In addition, re-infections can occur despite the presence of pre-existing immunity, suggesting that immunological memory to RSV is incomplete. To date, treatment of RSV infection is limited to the provision of supportive care and no effective vaccine is available. Although several are currently under investigation, these candidates focus upon the delivery of the F and G antigens of RSV to stimulate the immune system, rather than the internal antigens, which may provide cross protection between different subtypes of RSV. Vaccine development has been greatly hindered by the lack of an appropriate animal model in which to study vaccine efficacy and pneumovirus pathogenesis. Pneumonia virus of mice (PVM) is also a member of the Pneumovirus genus and, like RSV infection of humans, causes a bronchiolitis and fatal pneumonia in its natural host, the mouse. PVM has been proposed as an appropriate model system in which to both study pneumovirus pathogenesis and vaccine efficacy. The PVM model system was adapted to investigate a potential vaccination strategy to address the lack of an available RSV vaccine. Replication deficient recombinant adenovirus serotype 5 (rAd5) vectors were constructed which expressed the F, M and N genes of PVM J3666, in addition to a control construct, which expressed the LacZ gene of E. coli. The constructs were administered via the intranasal route to BALB/c mice and were able to elicit complete protection against a lethal dose of pathogenic PVM J3666, in both short-term experiments and in a long-term experiment, up to 20 weeks post immunisation. The protection effect elicited by the constructs was observed when administered in a single dose, and in alternative mouse strains, C3H/He-mg and C57BL/6, which had differing immunity haplotypes. The rAd5 vectors generated a PVM specific IgG humoral response to PVM and Ad5 antigen which did not correlate as the primary mediator of protection. The rAd5 candidate expressing the N gene of PVM was shown to induce IFNγ secreting T-cells. The use of a peptide library of PVM N protein determined that a specific response could be identified towards the amino acids N41-90, N81-130, N161-210 and N281-330. Thus, the PVM infection model of BALB/c mice provides an immunological platform to facilitate the study of RSV and PVM pathogenesis, immunology and vaccine development
    corecore