Functional Immune Alterations, Latent Herpesvirus Reactivation, Physiological Stress and Clinical Incidence Onboard the International Space Station

Functional Immune Alterations, Latent Herpesvirus Reactivation, Physiological Stress and Clinical Incidence Onboard the International Space Station

Kaposi’s sarcoma and multicentric Castleman Disease are HIV-related disease processes that are associated with human herpesvirus 8 (HHV-8) infection. Of particular concern is the growing incidence of drug resistance in immunocompromised patients, which stresses the urgency to develop new effective treatment alternatives. The collaboration will explore the potential of various combinations of agents, including Immune Design’s GLAASTM platform, with the goal to select the best potential immune therapy for patients. Though the extent of protection intrinsic immunity affords is still unknown, it is possible that intrinsic immunity may eventually be considered a third branch of the traditionally bipartite immune system. The Functional Immune Alterations, Latent Herpes Virus Reactivation, Physiological Stress and Clinical Incidence Onboard the International Space Station (Functional Immune) investigation builds on previous research completed during the Integrated Immune Study. This study analyzes ambient, live blood samples, frozen blood samples, saliva, and urine samples. Immunohistochemical studies revealed no significant cross-reactivity of the antibody toward human tissues.

GLA selectively binds to the TLR4 receptor and causes potent activation of dendritic cells (DCs) leading to the production of cytokines and chemokines that drive a Th1-type immune response. Also, like adaptive immunity, intrinsic immunity is specifically tailored to a single type or class of pathogens, notably retroviruses. Information obtained from this investigation can be used to assess the need for immune countermeasures to maintain and protect crew health on deep space missions. The Functional Immune Alterations, Latent Herpes Virus Reactivation, Physiological Stress and Clinical Incidence Onboard the International Space Station (Functional Immune) experiment is a comprehensive immunity flight investigation that uses longitudinally repeated measures to assess several aspects of immunity during long-duration spaceflight. However, infections may become chronic and result in physical disabilities, social exclusion, and psychological distress over time (1). Because of these attributes, the candidate is capable of eliciting a broad immune response, both a B-cell and T-cell response that is directed against the majority of the antigenic components of the virus. “Intrinsic immunity: a front-line defense against viral attack”.

Specialized preservatives may be utilized to assess comprehensive immunophenotype, gene expression, or proteomics. Measures of inflammation, stress, antimicrobial activity, etc. Not surprisingly, a particularly high prevalence of ACV resistance has been reported in immunocompromised patients being prophylactically treated with ACV for extended periods. Forward Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. PMID 15496950. Space Applications Previous research has shown crew members experience alterations in their immune systems during spaceflight, but this investigation is the first to examine unique immune-related changes, such as the distribution of white blood cells, particular aspects of innate immunity and reactivation of latent viruses. Biological changes are also compared with crew members’ self-reported information on stress, sleep disruption and other factors that are known to impact the immune system.
Functional Immune Alterations, Latent Herpesvirus Reactivation, Physiological Stress and Clinical Incidence Onboard the International Space Station

Although in nucleoside analog-resistant cases TK-independent drugs such as the viral DNA polymerase inhibitors foscarnet and cidofovir can be administered, these compounds frequently mediate severe toxic side effects, particularly in patients with high comorbidities. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the absence of guarantee that the product candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives, the Group’s ability to benefit from external growth opportunities, trends in exchange rates and prevailing interest rates, the impact of cost containment policies and subsequent changes thereto, the average number of shares outstanding as well as those discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2013. PMID 14985764. Understanding these subtle changes may help scientists pinpoint the onset of illness, and suggest monitoring strategies, or treatments, that can boost the immune system and prevent full-blown infections and diseases. Functional Immune requires 10 inflight subjects. Cell-to-cell spread enables HSV to bypass biophysical barriers and to circumvent classic neutralization by antibodies. Also a health questionnaire is completed.

PMID 12167863. In-flight at approximately mid-mission and Return (R)-1 day, blood samples are collected and are kept ambient and then returned to ground. Additionally urine and saliva samples are collected. Therefore, mutations in this epitope may render the virus noninfectious. Frozen blood, urine, and saliva samples are stored in the Minus Eighty-Degree Laboratory Freezer for ISS (MELFI) for return on the next available flight. 80 (8): 3863–71. Samples must be delivered to the Principal Investigator within 72 hours to avoid data loss, so blood should be drawn as close to hatch closure as possible, but no later than the end of crew day R-1.

Post-flight at R+1, R+30, R+90: blood, urine, and saliva samples are collected. To exploit this unique epitope for therapeutic interventions in humans, we generated a humanized derivative of mAb 2c as well as a chimeric version as control. Note: the R+90 session is conducted only if the R+30 results reveal active viral shedding. This study collects blood, urine, saliva samples, and data regarding general well-being via a Health Questionnaire. Blood samples are of the frozen and ambient type. Saliva samples are of two types: a rolled saliva sample and dry saliva samples. Hence, CDR coding gene segments of the murine donor-antibody 2c (i.e., 2c VL-CDR1/2/3 and 2c VH-CDR1/2/3) were grafted into acceptor frameworks coding for IGHV2-70 and IGKV2-40, respectively.

This occurs 4 times across 7 days and is associated with the blood collections. The dry saliva samples are collected using the Dry Saliva Booklet at prescribed intervals throughout the day for a total of 5 times. Each sample is collected on a separate page of the booklet corresponding to the prescribed time interval (Wake, Wake +30 min, Wake +6 hours, Wake +10 hours, Retire). The Dry Saliva Sample Booklet is allowed to air dry before stowing for return to ground. Because in a previous study we demonstrated that cross-linking of a type-common discontinuous epitope within the extracellular domain I of gB through mAb 2c plays a decisive role for its antiviral activity (20), we compared the chimeric and humanized antibody with the murine mAb 2c for binding specificity toward the conformation-dependent epitope within this unique functional region of HSV gB and applied a cell-based competition assay. The crewmember draws one additional 7.5 ml tube of urine per void for the Functional Immune experiment in addition to urine already being collected for the other experiment(s). The Health Questionnaire is completed on FD 15, and at mid-mission.

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