Greater Breadth of Vaccine-Induced Immunity in Females than Males Is Mediated by Increased Antibody Diversity in Germinal Center B Cells.

Inactivated influenza vaccines induce greater antibody responses in females than males among both humans and mice. To test the breadth of protection, we used recombinant mouse-adapted A/California/2009 (maA/Cal/09) H1N1 viruses containing mutations at one (1M), two (2M), or three (3M) antigenic sites, in addition to a virus containing the 1M mutation and a substitution of the Ca2 antigenic site (Sub) with one derived from an H5 hemagglutinin (HA) to challenge mice of both sexes. Following maA/Cal/09 vaccination, females produced greater virus-specific, class-switched total IgG and IgG2c antibodies against the vaccine and all mutant viruses, and antibodies from females recognized a greater number of unique, linear HA epitopes than did antibodies from males. While females had greater neutralizing antibody titers against the vaccine virus, both sexes showed a lower neutralization capacity against mutant viruses. After virus challenge, vaccinated females had lower pulmonary virus titers and reduced morbidity than males for the 1M and 2M viruses, but not the Sub virus. Females generated greater numbers of germinal center (GC) B cells containing superior somatic hypermutation (SHM) frequencies than vaccinated males. Deletion of activation-induced cytidine deaminase (Aicda) eliminated female-biased immunity and protection against the 2M virus. Harnessing methods to improve GC B cell responses and frequencies of SHM, especially in males, should be considered in the development of universal influenza vaccines. IMPORTANCE Adult females develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection would be dependent on the extent of virus diversity as well as molecular mechanisms in B cells which constrain the breadth of epitope recognition. We developed a panel of mouse-adapted (ma) A/Cal/09 viruses that had mutations in the immunodominant hemagglutinin. Following vaccination against maA/Cal/09, females were better able to neutralize maA/Cal/09 than males, but neutralization of mutant maA/Cal/09 viruses was equally poor in both sexes, despite vaccinated females being better protected against these viruses. Vaccinated females benefited from the greater production of class-switched, somatically hypermutated antibodies generated in germinal center B cells, which increased recognition of more diverse maA/Cal/09 hemagglutinin antigen epitopes. Female-biased protection against influenza infection and disease after vaccination is driven by differential mechanisms in males versus females and should be considered in the design of novel vaccine platforms.

Providing Quality of Care in Fragile and Vulnerable Settings: Lessons from South Sudan.

BACKGROUND: In 2020, the World Health Organization (WHO) released a report concerning planning and actions to provide quality of care in fragile, conflict-affected, and vulnerable areas. South Sudan, the world's newest country, has encountered both natural and man-made disasters in recent years that have posed marked challenges to delivery of care. The Southern Sudan Healthcare Organization (SSHCO) operates as a non-governmental organization (NGO) in this setting, delivering and improving healthcare through war, flooding, and infectious outbreaks. OBJECTIVE: The goal of this paper is to highlight the challenges faced in providing care in South Sudan from an NGO perspective and apply the recent WHO guidelines on quality of care to optimize practical implementation. METHOD: Each of the WHO's eight elements for quality of care in South Sudan were examined in relation to the experience of SSHCO from 2013-2021. Analysis included: 1. summary of the WHO element; 2. examples of successful implementation; 3. barriers to implementation; and 4. recommendations to improve implementation. FINDINGS: The team found that communication and coordination were the most important aspects of improving quality of care in South Sudan. These should be prioritized and include intergovernmental partners, the local and national Ministry of Health (MOH), NGOs, and community stakeholders. Communication and coordination should foster community engagement, improved data collecting and reporting, and sharing of publicly accessible information. Better clinical staff training and governance are also required to ensure the most effective use of limited resources. CONCLUSION: South Sudan faces many barriers to quality of care with communication and coordination identified among the foremost issues. Practical application of the WHO elements of quality of care can assist NGOs in effectively identifying areas for improvement to deliver better quality essential health services.

Fire at the Oakland Ghost Ship Warehouse: A disaster life cycle-based analysis.

OBJECTIVE: Structural fires remain a prominent threat to public health and safety even in several regions of the developed world, where rising housing costs force many to reside in unsafe environments. This case report of the Ghost Ship Warehouse fire in Oakland, California, highlights deficiencies in the emergency management system in the context of similar nightclub incidents to inform recommendations that might prevent such events from occurring in the future. DESIGN: The characteristics of the Ghost Ship warehouse and circumstances surrounding the fire, as described in government documents and news media sources, were examined using the disaster life cycle framework. The Ghost Ship fire was also compared with two prior fire disasters at the Happy Land nightclub in New York City and Station nightclub in West Warwick, Rhode Island. RESULTS: The following risk factors were identified as common features of deadly nightclub fires: large crowd size, limited access to exits, multiple code violations, lack of required permits, inadequate fire suppression systems, and poor building maintenance. CONCLUSIONS: To prevent the recurrence of such disasters, Oakland and other cities should adopt measures to improve interdepartmental communication; streamline reporting of fire and safety hazards, and allocate sufficient resources and staff capable of identifying hazardous buildings, performing inspections, and enforcing building and fire codes. Equally importantly, the urban affordable housing crisis needs to be adequately addressed to mitigate vulnerable populations living in unsafe dwellings that place them at risk of deadly fires.

Using mind mapping technology for personal preparedness planning.

OBJECTIVE: Organizing key information for personal disaster preparedness in an efficient and accessible format is critical to ensure practical utility. The authors examine the use of mind mapping technology to organize personal disaster preparedness information and explore the potential of mind mapping software as a tool to create individual and family preparedness resources. DESIGN: The general features of mind maps are considered and a sample family preparedness plan was created using TheBrain, a mind mapping software. RESULTS: Mind maps are a promising tool to organize personal preparedness plans with the ability to include significant amounts of varied information in a structure that emphasizes relationships between topics and enables collaborative sharing.