No abstract

Compassion Fatigue (CF) is commonly observed in professions associated with human and animal care. The COVID-19 pandemic compelled laboratory animal research institutions to implement new work practices in order to maintain essential animal care operations. These modifications ranged from shift changes to last-resort measures, such as culling animal colonies, to accommodate reduced staffing. Such changes could cause personnel to experience increased stress, isolation, and helplessness—all of which can increase CF risk. In the current study, 200 persons involved with animal research completed an online survey to gauge whether CF among laboratory animal personnel had increased during the pandemic. The survey examined professional quality of life, self-assessed levels of CF, institutional changes, perceived changes in animal welfare, and institutional measures intended to alleviate CF. A total of 86% of participants had experienced CF at some point in their career, with 41% experiencing a CF event (new or worsening symptoms of CF) during the pandemic. In addition, 90% of participants who reported a CF event also reported subsequent effects on their personal or professional lives. Health, employment, and animal-related stress that arose due to the pandemic were all found to influence CF scores significantly. Although 96% of respondents were considered essential workers, 67% did not feel as valued for their work as other essential personnel. Furthermore, 88% of personnel responsible for the euthanasia of healthy animals who experienced a CF event reported that CF also affected their personal life, professional life, or both, and 78% responded that interventions from internal CF programs or leadership did not help to alleviate symptoms of CF. The COVID-19 pandemic and resultant institutional changes will likely have lasting effects on persons and organizations. By determining and subsequently mitigating sources of CF, we can better assist the laboratory animal community during future crises.

Induction of mucosal IgA capable of providing a first line of defense against bacterial and viral pathogens remains a major goal of needle-free vaccines given via mucosal routes. Innate immune cells are known to play a central role in induction of IgA responses by mucosal vaccines, but the relative contribution of myeloid cell subsets to these responses has not firmly been established. Using an in vivo model of sublingual vaccination with Bacillus anthracis edema toxin (EdTx) as adjuvant, we examined the role of myeloid cell subsets for mucosal secretory IgA responses. Sublingual immunization of wild-type mice resulted in a transient increase of neutrophils in sublingual tissues and cervical lymph nodes. These mice later developed Ag-specific serum IgG responses, but not serum or mucosal IgA. Interestingly, EdTx failed to increase neutrophils in sublingual tissues of IKKβΔMye mice, and these mice developed IgA responses. Partial depletion of neutrophils before immunization of wild-type mice allowed the development of both mucosal and serum IgA responses. Finally, co-culture of B cells with neutrophils from either wild-type or IKKβΔMye mice suppressed production of IgA, but not IgM or IgG. These results identify a new role for neutrophils as negative regulators of IgA responses.

Anthrax is caused by Bacillus anthracis, a zoonotic bacterial pathogen affecting humans and livestock worldwide. The current human anthrax vaccine, anthrax vaccine adsorbed (AVA), is an injected vaccine with a cumbersome administration schedule and fails to promote mucosal immunity. Bacterial enterotoxins, which stimulate production of the cyclic nucleotide cAMP are effective experimental mucosal vaccine adjuvants, but their inherent toxicity has precluded their use in humans. We investigated whether cyclic dinucleotides that target Stimulator of Interferon Gamma Genes (STING) in mammalian cells could represent an alternative to bacterial enterotoxins as adjuvant for sublingual immunization and promotion of mucosal immunity and secretory IgA responses in addition to systemic immunity. We found that sublingual immunization of mice with Bacillus anthracis protective antigen (PA) and the STING ligand 3′3′-cGAMP promotes PA-specific serum IgG Ab responses of the same magnitude as those induced after immunization with PA and the experimental adjuvants cholera toxin (CT). Interestingly, this STING ligand also promoted serum anti-PA IgA and IgA-producing cells in the bone marrow. Furthermore, the saliva of mice immunized with the STING ligand exhibited similar levels of PA-specific IgA Abs as groups immunized with CT as adjuvant. The adjuvant activity of 3′3′-cGAMP was associated with mixed Th1, Th2, and Th17 responses. This STING ligand also induced rapid IFN-β and IL-10 responses in sublingual tissues and cervical lymph nodes, and TGF-β responses in the cervical lymph nodes, which could contribute to promoting IgA responses after sublingual immunization.