Obesity Is Associated with an Impaired Baseline Repertoire of Anti-Influenza Virus Antibodies.

Obesity is a risk factor for severe disease and mortality for both influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While previous studies show that individuals with obesity generate antibody responses following influenza vaccination, infection rates within the obese group were twice as high as those in the healthy-weight group. The repertoire of antibodies raised against influenza viruses following previous vaccinations and/or natural exposures is referred to here as baseline immune history (BIH). To investigate the hypothesis that obesity impacts immune memory to infections and vaccines, we profiled the BIH of obese and healthy-weight adults vaccinated with the 2010-2011 seasonal influenza vaccine in response to conformational and linear antigens. Despite the extensive heterogeneity of the BIH profiles in both groups, there were striking differences between obese and healthy subjects, especially with regard to A/H1N1 strains and the 2009 pandemic virus (Cal09). Individuals with obesity had lower IgG and IgA magnitude and breadth for a panel of A/H1N1 whole viruses and hemagglutinin proteins from 1933 to 2009 but increased IgG magnitude and breadth for linear peptides from the Cal09 H1 and N1 proteins. Age was also associated with A/H1N1 BIH, with young individuals with obesity being more likely to have reduced A/H1N1 BIH. We found that individuals with low IgG BIH had significantly lower neutralizing antibody titers than individuals with high IgG BIH. Taken together, our findings suggest that increased susceptibility of obese participants to influenza infection may be mediated in part by obesity-associated differences in the memory B-cell repertoire, which cannot be ameliorated by current seasonal vaccination regimens. Overall, these data have vital implications for the next generation of influenza virus and SARS-CoV-2 vaccines. IMPORTANCE Obesity is associated with increased morbidity and mortality from influenza and SARS-CoV-2 infection. While vaccination is the most effective strategy for preventing influenza virus infection, our previous studies showed that influenza vaccines fail to provide optimal protection in obese individuals despite reaching canonical correlates of protection. Here, we show that obesity may impair immune history in humans and cannot be overcome by seasonal vaccination, especially in younger individuals with decreased lifetime exposure to infections and seasonal vaccines. Low baseline immune history is associated with decreased protective antibody responses. Obesity potentially handicaps overall responses to vaccination, biasing it toward responses to linear epitopes, which may reduce protective capacity. Taken together, our data suggest that young obese individuals are at an increased risk of reduced protection by vaccination, likely due to altered immune history biased toward nonprotective antibody responses. Given the worldwide obesity epidemic coupled with seasonal respiratory virus infections and the inevitable next pandemic, it is imperative that we understand and improve vaccine efficacy in this high-risk population. The design, development, and usage of vaccines for and in obese individuals may need critical evaluation, and immune history should be considered an alternate correlate of protection in future vaccine clinical trials.

Obesity is associated with an altered baseline and post-vaccination influenza antibody repertoire.

As highlighted by the ongoing COVID-19 pandemic, vaccination is critical for infectious disease prevention and control. Obesity is associated with increased morbidity and mortality from respiratory virus infections. While obese individuals respond to influenza vaccination, what is considered a seroprotective response may not fully protect the global obese population. In a cohort vaccinated with the 2010-2011 trivalent inactivated influenza vaccine, baseline immune history and vaccination responses were found to significantly differ in obese individuals compared to healthy controls, especially towards the 2009 pandemic strain of A/H1N1 influenza virus. Young, obese individuals displayed responses skewed towards linear peptides versus conformational antigens, suggesting aberrant obese immune response. Overall, these data have vital implications for the next generation of influenza vaccines, and towards the current SARS-CoV-2 vaccination campaign.

Continuity and Access in an Academic Family Medicine Center.

BACKGROUND AND OBJECTIVES: A personal physician and enhanced access to care are principles of the patient-centered medical home. Despite the importance of these concepts, measuring and improving interpersonal continuity of care and access to care in academic family medicine centers has received little attention. The authors describe their program's methods and results to maximize continuity of care and minimize delays for care using proven principles from improvement science. METHODS: In 2004, a diverse quality improvement team from our family medicine center joined a breakthrough collaborative with other primary care practices focused on improving appointment access and continuity of care. We followed the model for improvement with a specific aim, explicit measures, and ambitious goals. The team adapted and applied principles from a change package presented in the collaborative to improve access and continuity. We planned and performed small tests of change that were subsequently optimized and spread to the entire practice. RESULTS: Average time to third available appointment for a routine physical improved from 22 days to 8 days. Average usual provider continuity (UPC) across all primary care physicians in the practice improved from 54% to 68%. Among resident physicians, UPC improved from 55% to 68%. These results have been sustained over 5 years. CONCLUSIONS: Despite multiple challenges in academic teaching practices, the continuous use of improvement methods to apply proven change concepts minimizes delay for care and maximizes continuity of care. The residency continuity practice can and should be a cornerstone of residency curriculum.

Overweight and obese adult humans have a defective cellular immune response to pandemic H1N1 influenza A virus.

OBJECTIVE: Obese adults have a greater risk of morbidity and mortality from infection with pandemic H1N1 influenza A virus (pH1N1). The objective of the present study was to elucidate the specific mechanisms by which obesity and overweight impact the cellular immune response to pH1N1. DESIGN AND METHODS: Peripheral blood mononuclear cells from healthy weight, overweight, and obese individuals were stimulated ex vivo with live pH1N1 and then markers of activation and function were measured using flow cytometry and cytokine secretion was measured using cytometric bead array assays. RESULTS: CD4(+) and CD8(+) T cells from overweight and obese individuals expressed lower levels of CD69, CD28, CD40 ligand, and interleukin-12 receptor, as well as, produced lower levels of interferon-γ and granzyme B, compared with healthy weight individuals, suggesting deficiencies in activation and function are indicated. Dendritic cells from the three groups expressed similar levels of major histocompatibility complex-II, CD40, CD80, and CD86, as well as, produced similar levels of interleukin-12. CONCLUSIONS: The defects in CD4(+) and CD8(+) T cells may contribute to the increased morbidity and mortality from pH1N1 in obese individuals. These data also provide evidence that both overweight and obesity cause impairments in immune function.