The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies, but immune responses conferring this protection are not yet ...elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 5 months after 2 doses, S IgG, S IgG Fc receptor-binding, and neutralising antibody responses waned significantly, yet neutralising antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ
and IL-2
CD8
T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ
and IL-2
CD4
and CD8
T cell responses in adolescents and adults were comparable or non-inferior. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, against Omicron BA.2, as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1, BA.2 and BA.5. Sera from 100 and 96% of adolescents tested at 1 and 5 months after two doses could also neutralise BA.1. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after three doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.
Structures (context of care delivery) and processes (actions aimed at delivery care) are posited to drive patient outcomes. Despite decades of primary care research, there remains a lack of evidence ...connecting specific structures/processes to patient outcomes to determine which of the numerous recommended structures/processes to prioritize for implementation. The objective of this study was to identify structures/processes most commonly present in high-performing primary care practices for chronic care management and prevention. We conducted key informant interviews with a national sample of 22 high-performing primary care practices. We identified the 10 most commonly present structures/processes in these practices, which largely enable 2 core functions: mobilizing staff to conduct patient outreach and helping practices avoid gaps in care. Given the costs of implementing and maintaining numerous structures/processes, our study provides a starting list for providers to prioritize and for researchers to investigate further for specific effects on patient outcomes.
Objectives
Enhanced inactivated influenza vaccines (eIIV) aim to increase immunogenicity and protection compared with the widely used standard IIV (S‐IIV).
Methods
We tested four vaccines in ...parallel, FluZone high dose, FluBlok and FluAd versus S‐IIV in a randomised controlled trial of older adults and in a mouse infection model to assess immunogenicity, protection from lethal challenge and mechanisms of action.
Results
In older adults, FluAd vaccination stimulated a superior antibody profile, including H3‐HA antibodies that were elevated for up to 1 year after vaccination, higher avidity H3HA IgG and larger HA stem IgG responses. In a mouse model, FluAd also elicited an earlier and larger induction of HA stem antibodies with increased germinal centre responses and upregulation and long‐term expression of B‐cell switch transcription factors. Long‐term cross‐reactive memory responses were sustained by FluAd following lethal heterosubtypic influenza challenge, with reduced lung damage and viral loads, coinciding with increased T‐ and B‐cell recall. Advantages were also noted for the high‐dose FluZone vaccine in both humans and mice.
Conclusion
The early, broadly reactive and long‐lived antibody response of FluAd indicates a potential advantage of this vaccine, particularly in years when there is a mismatch between the vaccine strain and the circulating strain of influenza viruses.
In this randomised clinical trial, we showed that enhanced influenza vaccines boost antibody quality in older adults, and showed a particular advantage of adjuvanted vaccines for long‐term high‐avidity and haemagglutinin‐stalk antibodies. This action translated to an increased protection by the same adjuvanted vaccines in mice for reduced viral loads and inflammation as a result of early and enhanced B‐cell recruitment and activation for antibody production.
Healthcare-associated infections, while preventable, result in increased morbidity and mortality in nursing home (NH) residents. Frontline personnel, such as certified nursing assistants (CNAs), are ...crucial to successful implementation of infection prevention and control (IPC) practices. The purpose of this study was to explore barriers to implementing and maintaining IPC practices for NH CNAs as well as to describe strategies used to overcome these barriers. We conducted a multi-site qualitative study of NH personnel important to infection control. Audio-recorded interviews were transcribed verbatim and transcripts were analyzed using conventional content analysis. Five key themes emerged as perceived barriers to effective IPC for CNAs: 1) language/culture; 2) knowledge/training; 3) per-diem/part-time staff; 4) workload; and 5) accountability. Strategies used to overcome these barriers included: translating in-services, hands on training, on-the-spot training for per-diem/part-time staff, increased staffing ratios, and inclusion/empowerment of CNAs. Understanding IPC barriers and strategies to overcome these barriers may better enable NHs to achieve infection reduction goals.
The Defense Coastal/Estuarine Research Program (DCERP) was a 10-year multi-investigator project funded by the Department of Defense to improve understanding of ecosystem processes and their ...interactions with natural and anthropogenic stressors at the Marine Corps Base Camp Lejeune (MCBCL) located in coastal North Carolina. The project was aimed at facilitating ecosystem-based management (EBM) at the MCBCL and other coastal military installations. Because of its scope, interdisciplinary character, and duration, DCERP embodied many of the opportunities and challenges associated with EBM, including the need for explicit goals, system models, long-term perspectives, systems complexity, change inevitability, consideration of humans as ecosystem components, and program adaptability and accountability. We describe key elements of this program, its contributions to coastal EBM, and its relevance as an exemplar of EBM.
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•Ecosystem based management (EBM) at coastal military installations requires cross-jurisdiction problem solving, long-term thinking, decision support tools, and adaptive management.•Interdisciplinary research programs like DCERP aiming to support EBM embody many of these same opportunities and challenges.•DCERP developed models to help sustain species diversity, assess impacts of current and future climate conditions on management strategies, and visualize sea level scenarios that could threaten military training land assets.•Program success was facilitated by the duration and intensity of this ecological program, close collaboration among all DCERP team scientists across ecological modules, and the input of MCBCL managers and local stakeholders.
Infections have been identified as a priority issue in nursing homes (NHs). We conducted a qualitative study purposively sampling 10 NHs across the country where 6–8 employees were recruited ...(N = 73). Semi-structured, open-ended guides were used to conduct in-depth interviews. Data were audiotaped, transcribed and a content analysis was performed. Five themes emerged: ‘Residents' Needs’, ‘Roles and Training’ ‘Using Infection Data,’ ‘External Resources’ and ‘Focus on Hand Hygiene.’ Infection prevention was a priority in the NHs visited. While all sites had hand hygiene programs, other recommended areas were not a focus and many sites were not aware of available resources. Developing ways to ensure effective, efficient and standardized infection prevention and control in NHs continues to be a national priority.
Background
Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be ...equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents.
Methods
Participants aged 11–17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13–42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively.
Results
Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool-specific interleukin-2 (IL-2)
+
CD4
+
, SNM-specific IL-2
+
CD8
+
, S-specific IL-2
+
CD8
+
, N-specific IL-2
+
CD4
+
, N-specific IL-2
+
CD8
+
and M-specific IL-2
+
CD4
+
responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2
+
CD4
+
, interferon-γ
+
CD8
+
and IL-2
+
CD8
+
responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions.
Conclusion
This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.
Graphical abstract
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