Influence of microbial antigen formulation and delivery route on the immune response

Recent technological advances have resulted in the production of safe subunit and synthetic small peptide vaccines. Unfortunately, these vaccines are weakly or non-immunogenic in the absence of an immunological adjuvant (agents that can induce strong immunity to antigens). In addition, in order to prevent and/or control infection at the mucosal surface, stimulation of the mucosal immune system is essential. This may be achieved via the common mucosal immune system by exposure to antigen at a mucosal surface remote from the area of infection. Initial studies investigated the potential of multiple emulsions in effecting oral absorption and the subsequent immune responses to a lipopolysaccharide vaccine (LPS) after immunisation. Nasal delivery of LPS was carried out in parallel work using either aqueous solution or gel formulations. Tetanus toxoid vaccine in simple solution was delivered to guinea pigs as free antigen or entrapped in DSPC liposomes. In addition, adsorbed tetanus toxoid vaccine was delivered nasally free or in an aerosil gel formulation. This work was extended to investigate guinea pigs immunised by various mucosal routes with a herpes simplex virus subunit vaccine prepared from virus infected cells and delivered in gels, multiple emulsions and liposomes. Comparable serum antibody responses resulted but failed to produce enhanced protection against vaginal challenge when compared to subcutaneous immunisation with alhydrogel adjuvanted vaccine. Thus, immunisation of the mucosal surface by these methods may have been inadequate. These studies were extended in an attempt to protect against HSV genital challenge by construction of an attenuated Salmonella typhimurium HWSH aroA mutant expressing a cloned glycoprotein D-l gene fused to the Es-cherichia coli lac z promoter. Preliminary work on the colonisation of guinea pigs with S. typhimurium HWSH aroA mutants were carried out, with the aim of using the guinea pig HSV vaginal model to investigate protection

New Pathways for Alimentary Mucositis

Alimentary mucositis is a major dose-limiting toxicity associated with anticancer treatment. It is responsible for reducing patient quality of life and represents a significant economic burden in oncology. The pathobiology of alimentary mucositis is extremely complex, and an increased understanding of mechanisms and pathway interactions is required to rationally design improved therapies. This review describes the latest advances in defining mechanisms of alimentary mucositis pathobiology in the context of pathway activation. It focuses particularly on the recent genome-wide analyses of regimen-related mucosal injury and the identification of specific regulatory pathways implicated in mucositis development. This review also discusses the currently known alimentary mucositis risk factors and the development of novel treatments. Suggestions for future research directions have been raised

Systematic Review of Laser and Other Light Therapy for the Management of Oral Mucositis in Cancer Patients

Background The aim of this study was to review the available literature and define clinical practice guidelines for the use of laser and other light therapies for the prevention and treatment of oral mucositis. Methods A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based onthe evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible. Results A new recommendation was made for low-level laser (wavelength at 650 nm, power of 40 mW, and each square centimeter treated with the required time to a tissue energy dose of 2 J/cm2 (2 s/point)) for the prevention of oral mucositis in adult patients receiving hematopoietic stem cell transplantation conditioned with high-dose chemotherapy, with or without total body irradiation. A new suggestion was made for low-level laser (wavelength around 632.8 nm) for the prevention of oral mucositis in patients undergoing radiotherapy, without concomitant chemotherapy, for head and neck cancer. No guideline was possible in other populations and for other light sources due to insufficient evidence. Conclusions The increasing evidence in favor of low-level laser therapy allowed for the development of two new guidelines supporting this modality in the populations listed above. Evidence for other populations was also generally encouraging over a range of wavelengths and intensities. However, additional well-designed research is needed to evaluate the efficacy of laser and other light therapies in various cancer treatment settings

Allergen-specific T cell quantity in blood is higher in allergic compared to nonallergic individuals

Article deposited according to agreement with BMC, December 6, 2010.YesFunding provided by the Open Access Authors Fund

The microbiota-gut-brain axis:An emerging therapeutic target in chemotherapy-induced cognitive impairment

Chemotherapy-induced cognitive impairment (CICI) is an ill-defined complication of chemotherapy treatment that places a significant psychosocial burden on survivors of cancer and has a considerable impact on the activities of daily living. CICI pathophysiology has not been clearly defined, with candidate mechanisms relating to both the direct cytotoxicity of chemotherapy drugs on the central nervous system (CNS) and more global, indirect mechanisms such as neuroinflammation and blood brain barrier (BBB) damage. A growing body of research demonstrates that changes to the composition of the gastrointestinal microbiota is an initiating factor in numerous neurocognitive conditions, profoundly influencing both CNS immunity and BBB integrity. Importantly, chemotherapy causes significant disruption to the gastrointestinal microbiota. While microbial disruption is a well-established factor in the development of chemotherapy-induced gastrointestinal toxicities (largely diarrhoea), its role in CICI remains unknown, limiting microbial-based therapeutics or risk prediction strategies. Therefore, this review aims to synthesise and critically evaluate the evidence addressing the microbiota-gut-brain axis as a critical factor influencing the development of CICI

NNAWG Meeting Minutes

Items discussed: Tribal School/UNO future educational partnerships; joint research and grant writing opportunities; scholarship opportunities and funding mechanisms; curriculum development for improving K - 12 mathematics, science, and technology education through the use of aeronautics; faculty enhancement workshops; development of a Nebraska Model of Best Practice; and future interstate, regional, and national Native American/NASA Space Grant initiatives. Asa result of this meeting, a number of annual scholarships and organizational enhancements were provided to the 2 tribal colleges and the 4 reservations schools. The working group met several times within the next few years and continues to maintain close contact with other members. In fact, it was not until this first UNO meeting that many of the administrators had ever met jointly to discuss pressing problems and possible partnerships

Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

Background: Mucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity. Methods: Thirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry. Results: Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy. Conclusions: Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.Zhi Yi Ong, Rachel J. Gibson, Joanne M. Bowen, Andrea M. Stringer, Jocelyn M. Darby, Richard M. Logan, Ann S.J. Yeoh, Dorothy M. Keef