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BACKGROUND: The growing field of commercial human spaceflight includes novel considerations for the aerospace medicine specialist. These include the aeromedical evaluation of individuals from diverse backgrounds and with a wide array of medical conditions, as well as understanding key stakeholders and operational goals of the commercial spaceflight company. With this in mind, aerospace medicine resident education through commercial space companies provide broad benefit to future flight surgeons and aerospace medicine specialists. OVERVIEW: University of Texas Medical Branch aerospace medicine residents have opportunities to rotate at Axiom Space and complete projects under the guidance of an Axiom flight surgeon. One particular experience involved leveraging preventive medicine principles in the evaluation and analysis of current infectious disease and public health threats as part of a developing pre-launch health stabilization program. The experience involved data-gathering and stakeholder analysis including considerations for participation of commercial spaceflight to the International Space Station, as well as considering future implications for end-to-end commercial missions. DISCUSSION: This learning opportunity highlighted some of the unique considerations of the conduct of human spaceflight and aerospace medicine as part of a commercial space company. By contributing directly to discussion and development of a knowledge base and program at the commercial company, this experience not only provided real-time benefit to the company but also gave essential exposure to the duties of commercial space flight surgeons and thus increased future competence. Learning Objectives 1. The participant will understand the expanded and specific learning opportunities possible for aerospace medicine residents at commercial space companies. 2. The participant will understand the importance of integrated aerospace medicine resident education at commercial space companies for future employee competence. 3. The participant will understand the mutual benefits for aerospace medicine resident and commercial space companies when commercial space companies integrate supervised and mentored aerospace medicine education. [ABSTRACT FROM AUTHOR]

INTRODUCTION: This case report describes a 40-60 year-old astronaut seeking a waiver after a small bowel obstruction status post-lysis of adhesions. The individual had a past medical history of appendicitis status post open appendectomy as a young child complicated by a small bowel obstruction (SBO) approximately 20 years later treated with laparotomy and adhesion release. They were previously granted a waiver for long duration spaceflight. They developed another SBO and underwent laparoscopic adhesiolysis without complication. After recovery, they were evaluated for certification for long-duration spaceflight. BACKGROUND: SBOs are a common complication of intra-abdominal surgery due to the formation of adhesions. SBOs can be treated conservatively with oral intake restriction, rehydration, and symptom management but may be treated with surgical intervention. Recurrence of an SBO is common but less frequent with operative intervention. Screening for adhesions predisposing an individual to recurrence are not commonly performed. Case Presentation: After recovery, this individual underwent evaluation for long-duration spaceflight. Outside of prior abdominal surgeries they had no other complicating medical conditions. Due to the concern for recurrence of SBO, the individual underwent additional screening evaluation for adhesions via abdominal ultrasound evaluation which showed "visceral slide" and did not find evidence of bowel adhesions. The astronaut was presented to the Multilateral Space Medical Board and granted certification for long-duration spaceflight. DISCUSSION: This case presentation describes a common complication of intra-abdominal surgery, SBO, and one process for evaluation for qualification for spaceflight. Intra-abdominal surgery is a common operation that an individual may undergo for a variety of conditions, including childhood surgery for appendicitis. Any individual with a history of prior intra-abdominal surgery is at risk for a small bowel obstruction and prior SBO puts an individual at risk for recurrence. An SBO in spaceflight would put the individual at risk of uncontrollable nausea and vomiting, dehydration, and be potentially mission ending. Possible adhesions and SBOs can be diagnosed with ultrasound. Risk reduction and prediction of recurrence is important for safety of the individual and the mission. Learning Objectives 1. The participant will understand the potential risks of a prior small bowel obstruction during medical evaluation for spaceflight. 2. The participant will understand one possible method of evaluation of a crewmember with a history of a small bowel obstruction for certification for spaceflight. [ABSTRACT FROM AUTHOR]

Influenza remains a worldwide public health threat. Although seasonal influenza vaccines are currently the best means of preventing severe disease, the standard-of-care vaccines require frequent updating due to antigenic drift and can have low efficacy, particularly in vulnerable populations. Here, we demonstrate that a single administration of a recombinant adenovirus-associated virus (rAAV) vector expressing a computationally optimized broadly reactive antigen (COBRA)-derived influenza H1 hemagglutinin (HA) induces strongly neutralizing and broadly protective antibodies in naïve mice and ferrets with pre-existing influenza immunity. Following a lethal viral challenge, the rAAV-COBRA vaccine allowed for significantly reduced viral loads in the upper and lower respiratory tracts and complete protection from morbidity and mortality that lasted for at least 5 months post-vaccination. We observed no signs of antibody waning during this study. CpG motif enrichment of the antigen can act as an internal adjuvant to further enhance the immune responses to allow for lower vaccine dosages with the induction of unique interferon-producing CD4+ and CD8+ T cells specific to HA head and stem peptide sequences. Our studies highlight the utility of rAAV as an effective platform to improve seasonal influenza vaccines. IMPORTANCE Developing an improved seasonal influenza vaccine remains an ambitious goal of researchers and clinicians alike. With influenza routinely causing severe epidemics with the potential to rise to pandemic levels, it is critical to create an effective, broadly protective, and durable vaccine to improve public health worldwide. As a potential solution, we created a rAAV viral vector expressing a COBRA-optimized influenza hemagglutinin antigen with modestly enriched CpG motifs to evoke a robust and long-lasting immune response after a single intramuscular dose without needing boosts or adjuvants. Importantly, the rAAV vaccine boosted antibody breadth to future strains in ferrets with pre-existing influenza immunity. Together, our data support further investigation into the utility of viral vectors as a potential avenue to improve our seasonal influenza vaccines. [ABSTRACT FROM AUTHOR]

Recombinant adeno-associated virus (rAAV) vectors are increasingly being used for clinical gene transfer and have shown great potential for the treatment of several monogenic disorders. However, contaminant DNA from producer plasmids can be packaged into rAAV alongside the intended expression cassette-containing vector genome. The consequences of this are unknown. Our analysis of rAAV preps revealed abundant contaminant sequences upstream of the AAV replication (Rep) protein driving promoter, P5, on the Rep-Cap producer plasmid. Characterization of P5-associated contaminants after infection showed transfer, persistence, and transcriptional activity in AAV-transduced murine hepatocytes, in addition to in vitro evidence suggestive of integration. These contaminants can also be efficiently translated and immunogenic, revealing previously unrecognized side effects of rAAV-mediated gene transfer. P5-associated contaminant packaging and activity were independent of an inverted terminal repeat (ITR)-flanked vector genome. To prevent incorporation of these potentially harmful sequences, we constructed a modified P5-promoter (P5-HS), inserting a DNA spacer between an Rep binding site and an Rep nicking site in P5. This prevented upstream DNA contamination regardless of transgene or AAV serotype, while maintaining vector yield. Thus, we have constructed an rAAV production plasmid that improves vector purity and can be implemented across clinical rAAV applications. These findings represent new vector safety and production considerations for rAAV gene therapy., Competing Interests: M.A.B., P.-H.C., C.L.M., and A.M.D. are listed inventors on a provisional patent that includes the P5-HS design described in this article. A.M.D. and A.C.N. are listed inventors on patents relating to FVIII and FIX construct designs for AAV gene therapy and are entitled to royalty income from their licensing. A.C.N. acts as an advisor for Freeline Therapeutics, BioMarin Pharmaceutical, and Generation Bio; is a founder of, has a sponsored research agreement with, and owns equity in Freeline Therapeutics; and is a consultant to several biopharmaceutical companies. J.T.G. possesses equity in Vertex Pharmaceuticals and is entitled to royalty income from patents related to gene therapy technology., (© 2022 The Authors.)