Impact of diabetes status on immunogenicity of trivalent inactivated influenza vaccine in older adults.

Individuals with type 2 diabetes mellitus experience high rates of influenza virus infection and complications. We compared the magnitude and duration of serologic response to trivalent influenza vaccine in adults aged 50-80 with and without type 2 diabetes mellitus. Serologic response to influenza vaccination was similar in both groups: greater fold-increases in antibody titer occurred among participants with lower pre-vaccination antibody titers. Waning of antibody titers was not influenced by diabetes status.

Personal Network Inference Unveils Heterogeneous Immune Response Patterns to Viral Infection in Children with Acute Wheezing.

Human rhinovirus (RV)-induced exacerbations of asthma and wheeze are a major cause of emergency room presentations and hospital admissions among children. Previous studies have shown that immune response patterns during these exacerbations are heterogeneous and are characterized by the presence or absence of robust interferon responses. Molecular phenotypes of asthma are usually identified by cluster analysis of gene expression levels. This approach however is limited, since genes do not exist in isolation, but rather work together in networks. Here, we employed personal network inference to characterize exacerbation response patterns and unveil molecular phenotypes based on variations in network structure. We found that personal gene network patterns were dominated by two major network structures, consisting of interferon-response versus FCER1G-associated networks. Cluster analysis of these structures divided children into subgroups, differing in the prevalence of atopy but not RV species. These network structures were also observed in an independent cohort of children with virus-induced asthma exacerbations sampled over a time course, where we showed that the FCER1G-associated networks were mainly observed at late time points (days four-six) during the acute illness. The ratio of interferon- and FCER1G-associated gene network responses was able to predict recurrence, with low interferon being associated with increased risk of readmission. These findings demonstrate the applicability of personal network inference for biomarker discovery and therapeutic target identification in the context of acute asthma which focuses on variations in network structure.

Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial.

Importance: Antibody blockade of activin type II receptor (ActRII) signaling stimulates skeletal muscle growth. Previous clinical studies suggest that ActRII inhibition with the monoclonal antibody bimagrumab also promotes excess adipose tissue loss and improves insulin resistance. Objective: To evaluate the efficacy and safety of bimagrumab on body composition and glycemic control in adults with type 2 diabetes and overweight and obesity. Design, Setting, and Participants: This double-masked, placebo-controlled, 48-week, phase 2 randomized clinical trial was conducted among adults with type 2 diabetes, body mass index between 28 and 40, and glycated hemoglobin (HbA1c) levels between 6.5% and 10.0% at 9 US and UK sites. The trial was conducted from February 2017 to May 2019. Only participants who completed a full treatment regimen were included in analysis. Interventions: Patients were randomized to intravenous infusion of bimagrumab (10 mg/kg up to 1200 mg in 5% dextrose solution) or placebo (5% dextrose solution) treatment every 4 weeks for 48 weeks; both groups received diet and exercise counseling. Main Outcomes and Measures: The primary end point was least square mean change from baseline to week 48 in total body fat mass (FM); secondary and exploratory end points were lean mass (LM), waist circumference (WC), HbA1c level, and body weight (BW) changes from baseline to week 48. Results: A total of 75 patients were randomized to bimagrumab (n = 37; 23 [62.2%] women) or placebo (n = 38; 12 [31.6%] women); 58 (77.3%) completed the 48-week study. Patients at baseline had a mean (SD) age of 60.4 (7.7) years; mean (SD) BMI of 32.9 (3.4); mean (SD) BW of 93.6 (14.9) kg; mean (SD) FM of 35.4 (7.5) kg; and mean (SD) HbA1c level of 7.8% (1.0%). Changes at week 48 for bimagrumab vs placebo were as follows: FM, -20.5% (-7.5 kg [80% CI, -8.3 to -6.6 kg]) vs -0.5% (-0.18 kg [80% CI, -0.99 to 0.63 kg]) (P < .001); LM, 3.6% (1.70 kg [80% CI, 1.1 to 2.3 kg]) vs -0.8% (-0.4 kg [80% CI, -1.0 to 0.1 kg]) (P < .001); WC, -9.0 cm (80% CI, -10.3 to -7.7 cm) vs 0.5 cm (80% CI, -0.8 to 1.7 cm) (P < .001); HbA1c level, -0.76 percentage points (80% CI, -1.05 to -0.48 percentage points) vs -0.04 percentage points (80% CI, -0.23 to 0.31 percentage points) (P = .005); and BW, -6.5% (-5.9 kg [80% CI, -7.1 to -4.7 kg]) vs -0.8% (-0.8 kg [80% CI, -1.9 to 0.3 kg]) (P < .001). Bimagrumab's safety and tolerability profile was consistent with prior studies. Conclusions and Relevance: In this phase 2 randomized clinical trial, ActRII blockade with bimagrumab led to significant loss of FM, gain in LM, and metabolic improvements during 48 weeks in patients with overweight or obesity who had type 2 diabetes. ActRII pathway inhibition may provide a novel approach for the pharmacologic management of excess adiposity and accompanying metabolic disturbances. Trial Registration: ClinicalTrials.gov number: NCT03005288.

Adverse Events Among Young Adults Following a Third Dose of Measles-Mumps-Rubella Vaccine.

BACKGROUND: A third measles-mumps-rubella vaccine (MMR) dose (MMR3) is recommended in the United States for persons at increased risk for mumps during outbreaks. MMR3 is also likely given to persons who might have received 2 doses of MMR but lack documentation. Since MMR3 safety data are limited, we describe adverse events in persons receiving MMR3 in a nonoutbreak setting. METHODS: Young adults with 2 documented MMR doses were administered MMR3. From 2 weeks before until 4 weeks after MMR3 receipt, participants reported daily on 11 solicited, common symptoms potentially associated with MMR. Weekly rate differences in post- vs prevaccination (baseline) were evaluated by Poisson regression. Baseline rates were subtracted from postvaccination rates of significantly different symptoms to estimate the number and percentage of participants with excess risk for symptoms post-MMR3. Descriptive analyses were performed for 3 postvaccination injection-site symptoms. RESULTS: The 662 participants were aged 18-28 years (median = 20 years); 56% were women. Headache, joint problems, diarrhea, and lymphadenopathy rates were significantly higher postvaccination vs baseline. We estimate that 119 participants (18%) reported more symptoms after MMR3 than prevaccination. By symptom, 13%, 10%, 8%, and 6% experienced increased symptoms of headache, joint problems, diarrhea, and lymphadenopathy, respectively, after MMR3. The median onset was Days 3-6 postvaccination; the median duration was 1-2 days. One healthcare visit for a potential vaccination-related symptom (urticaria) was reported. Injection-site symptoms were reported by 163 participants (25%); the median duration was 1-2 days. CONCLUSIONS: Reported systemic and local events were mild and transient. MMR3 is safe and tolerable among young adults.

Bimagrumab vs Optimized Standard of Care for Treatment of Sarcopenia in Community-Dwelling Older Adults: A Randomized Clinical Trial.

Importance: The potential benefit of novel skeletal muscle anabolic agents to improve physical function in people with sarcopenia and other muscle wasting diseases is unknown. Objective: To confirm the safety and efficacy of bimagrumab plus the new standard of care on skeletal muscle mass, strength, and physical function compared with standard of care alone in community-dwelling older adults with sarcopenia. Design, Setting, and Participants: This double-blind, placebo-controlled, randomized clinical trial was conducted at 38 sites in 13 countries among community-dwelling men and women aged 70 years and older meeting gait speed and skeletal muscle criteria for sarcopenia. The study was conducted from December 2014 to June 2018, and analyses were conducted from August to November 2018. Interventions: Bimagrumab 700 mg or placebo monthly for 6 months with adequate diet and home-based exercise. Main Outcomes and Measures: The primary outcome was the change in Short Physical Performance Battery (SPPB) score after 24 weeks of treatment. Secondary outcomes included 6-minute walk distance, usual gait speed, handgrip strength, lean body mass, fat body mass, and standard safety parameters. Results: A total of 180 participants were recruited, with 113 randomized to bimagrumab and 67 randomized to placebo. Among these, 159 participants (88.3%; mean [SD] age, 79.1 [5.3] years; 109 [60.6%] women) completed the study. The mean SPPB score increased by a mean of 1.34 (95% CI, 0.90 to 1.77) with bimagrumab vs 1.03 (95% CI, 0.53 to 1.52) with placebo (P = .13); 6-minute walk distance increased by a mean of 24.60 (95% CI, 7.65 to 41.56) m with bimagrumab vs 14.30 (95% CI, -4.64 to 33.23) m with placebo (P = .16); and gait speed increased by a mean of 0.14 (95% CI, 0.09 to 0.18) m/s with bimagrumab vs 0.11 (95% CI, 0.05 to 0.16) m/s with placebo (P = .16). Bimagrumab was safe and well-tolerated and increased lean body mass by 7% (95% CI, 6% to 8%) vs 1% (95% CI, 0% to 2%) with placebo, resulting in difference of 6% (95% CI, 4% to 7%) (P < .001). Conclusions and Relevance: This randomized clinical trial found no significant difference between participants treated with bimagrumab vs placebo among older adults with sarcopenia who had 6 months of adequate nutrition and light exercise, with physical function improving in both groups. Bimagrumab treatment was safe, well-tolerated, increased lean body mass, and decreased fat body mass. The effects of sarcopenia, an increasing cause of disability in older adults, can be reduced with proper diet and exercise. Trial Registration: ClinicalTrials.gov Identifier: NCT02333331; EudraCT number: 2014-003482-25.

Rubella virus neutralizing antibody response after a third dose of measles-mumps-rubella vaccine in young adults.

BACKGROUND: Third doses of measles-mumps-rubella (MMR) vaccine have been administered during mumps outbreaks and in various non-outbreak settings. The immunogenicity of the rubella component has not been evaluated following receipt of a third dose of MMR vaccine. METHODS: Young adults aged 18-31 years with documented two doses of MMR vaccine received a third dose of MMR vaccine between July 2009 and October 2010. Rubella neutralizing antibody titers were assessed before, 1 month, and 1 year after receipt of a third dose of MMR vaccine. RESULTS: Among 679 participants, 1.8% had rubella antibody titers less than 10 U/ml, immediately before vaccination, approximately 15 years after receipt of a second dose of MMR vaccine. One month after receipt of a third dose of MMR vaccine, average titers were 4.5 times higher and >50% of participants had a 4-fold boost. Response was highest among those with titers less than 10 U/ml prior to vaccination (geometric mean titer ratio = 18.8; 92% seroconversion) and decreased with increasing pre-vaccination titers. Average titers declined 1 year postvaccination but remained significantly higher than pre-vaccination levels. The proportion classified as low-positive antibody levels increased from 3% 1 month postvaccination to 24% 1 year postvaccination. CONCLUSIONS: Vaccination with a third dose of MMR vaccine resulted in a robust boosting of rubella neutralizing antibody response that remained elevated 1 year later. Young adults with low rubella titers are more likely to benefit from a third dose of MMR vaccine.

Comparing Reported Dietary Supplement Intakes between Two 24-Hour Recall Methods: The Automated Self-Administered 24-Hour Dietary Assessment Tool and the Interview-Administered Automated Multiple Pass Method.

BACKGROUND: The Automated Self-Administered 24-hour Dietary Assessment Tool (ASA24) includes a highly standardized multipass web-based recall that, like the Automated Multiple Pass Method (AMPM), captures detailed information about dietary intake using multiple probes and reminders to enhance recall of intakes. The primary distinction between ASA24 and AMPM is that the ASA24 user interface guides participants, thus removing the need for interviewers. OBJECTIVE: The objective of this study was to compare dietary supplement use reported on self-administered (ASA24-2011) vs interviewer-administered (AMPM) 24-hour recalls. DESIGN: The Food Reporting Comparison Study was an evaluation study designed to compare self-reported intakes captured using the self-administered ASA24 vs data collected via interviewer-administered AMPM recalls. Between 2010 and 2011, 1081 women and men were enrolled from three integrated health care systems that belong to the National Cancer Institute-funded Cancer Research Network: Security Health Plan Marshfield Clinic, Wisconsin; Henry Ford Health System, Michigan; and Kaiser Permanente Northern California, California. Quota sampling was used to ensure a balance of age, sex, and race/ethnicity. Participants were randomly assigned to four groups, and each group was asked to complete two dietary recalls: group 1, two ASA24s; group 2, two AMPMs; group 3, ASA24 first and AMPM second; and group 4, AMPM first and ASA24 second. Dietary supplements were coded using the 2007-2008 National Health and Nutrition Examination Survey Dietary Supplement Database. Analyses used the two one-sided tests, known as TOST, to assess equivalence of reported supplement use between methods. RESULTS: Complete 24-hour dietary recalls that included both dietary and supplement intake data were available for 1076 participants (507 men and 569 women). The proportions reporting supplement use via ASA24 and AMPM were 46% and 43%, respectively. These proportions were equivalent, with a small effect size of less than 20%. There were two exceptions in subgroup analyses: reported use among those 40 to 59 years of age and reported use by non-Hispanic black subjects were higher for ASA24 than AMPM. CONCLUSIONS: This study provides evidence that there is little difference in reported supplement use by mode of administration (ie, interview-administered vs self-administered recall).

Comparison of recruitment and retention among demographic subgroups in a large diverse population study of diet.

OBJECTIVE: We examined the feasibility of conducting a longitudinal study of diet among diverse populations by comparing rates of response throughout recruitment and retention phases by demographic and other characteristics. METHODS: Using quota sampling, participants were recruited from 3 geographically and demographically diverse integrated health systems in the United States. Overall, 12,860 adults, ages 20-70, were invited to participate via mail. Participation first required accessing the study's website and later meeting eligibility criteria via telephone interview. Enrollees were asked to provide two 24-hour dietary recalls, either interviewer-administered or self-administered on the web, over 6 weeks. Stepped monetary incentives were provided. RESULTS: Rates for accessing the study website ranged from 6% to 23% (9% overall) across sites. Site differences may reflect differences in recruitment strategy or target samples. Of those accessing the website, enrollment was high (≥ 87%). Of the 1185 enrollees, 42% were non-Hispanic white, 34% were non-Hispanic black, and 24% were Hispanic. Men and minorities had lower enrollment rates than women and non-Hispanic whites, partially due to less successful telephone contact for eligibility screening. Once enrolled, 90% provided 1 recall and 80% provided both. Women had higher retention rates than men, as did older compared to younger participants. Retention rates were similar across race/ethnicity groups. CONCLUSIONS: While study recruitment remains challenging, once recruited most participants, regardless of race/ethnicity, completed two 24-hour dietary recalls, both interviewer-administered and self-administered on the web. This study demonstrates the feasibility of collecting multiple 24-hour recalls including less expensive automated self-administered recalls among diverse populations.

Mumps Virus Nucleoprotein and Hemagglutinin-Specific Antibody Response Following a Third Dose of Measles Mumps Rubella Vaccine.

BACKGROUND: Recent mumps outbreaks among 2-dose measles mumps rubella (MMR) vaccine recipients have raised questions regarding the potential benefits of a third dose of vaccine (MMR3). If MMR3 provides a sustained elevation in mumps antibody, it may be beneficial for certain at-risk groups or as an outbreak control measure. METHODS: Sera were collected immediately prior to MMR3 and at 1 month and 1 year post-MMR3 from 656 healthy adults aged 18-28 years in a nonoutbreak setting. Immunoglobulin G (IgG) was measured by enzyme-linked immunosorbent assay (ELISA) using whole mumps virus (commercial ELISA), hemagglutinin (HN; major neutralizing target), and nucleoprotein (NP; immunodominant) antigens. ELISA measurements were compared with in vitro plaque reduction neutralization (PRN) titers, and baseline antibody was compared with post-MMR3 levels. RESULTS: There were modest but statistically significant (P < .05) increases in mumps antibody at 1 month post-MMR3 by all 3 ELISA methods and by PRN titer. At 1 year post-MMR3, mumps antibody declined toward baseline but remained elevated (P < .05). The correlation between PRN titers and ELISA measurements was poor (r2 = .49), although sera with the highest amount of HN IgG also had the highest PRN titers. CONCLUSIONS: Individuals with the lowest baseline PRN titers had the largest increase in frequency of samples that became positive for HN and NP by ELISA. A third dose of MMR may benefit certain individuals with a low level of mumps virus-neutralizing antibody, especially in the context of an outbreak or other high-risk setting. Additionally, poor correlation among serologic tests does not allow effective prediction of PRN titer by ELISA.

Seasonal Influenza Vaccination of Children Induces Humoral and Cell-Mediated Immunity Beyond the Current Season: Cross-reactivity With Past and Future Strains.

BACKGROUND: Influenza viruses gradually accumulate point mutations, reducing the effectiveness of prior immune protection. METHODS: Children aged 9-14 years received 2010-2011 trivalent inactivated influenza vaccine (TIV). Vaccination history, hemagglutination-inhibition (HI) titers, and cell-mediated immune responses were assessed to investigate the cross-reactivity with past and future influenza virus strains. RESULTS: 2010-2011 TIV induced significant T-cell responses and HI titers of ≥160, with a fold-rise of ≥4 and titers of ≥100 maintained for >7 months in the majority of children. Pre-existing memory B cells in these children differentiated quickly to antibody-secreting cells to the new vaccine antigens. Children vaccinated in the previous year maintained high HI titers well into 2010, demonstrating elevated HI titers against A/Perth/16/2009, the future (in 2010-2011) H3N2 component. Prior vaccination enhanced CD8+ T-cell responses to A/Perth/16/2009. Children vaccinated with the prior 2009-2010 seasonal vaccine also demonstrated higher preexisting levels of interferon γ-secreting CD4+CD69+ T cells to 2009 pandemic influenza A(H1N1). Children previously vaccinated with 2009-2010 seasonal influenza vaccine also showed greater expansion of tumor necrosis factor α-secreting CD8+CD69+ T cells to 2009 pandemic influenza A(H1N1) upon vaccination in the 2010-2011 season than those who were not previously vaccinated. CONCLUSIONS: Seasonal influenza viruses continuously drift, which allows them to circumvent protective immunity, but conserved epitopes provide immunological cross-reactivity in children through either vaccination directly or through prime/boost in the prior influenza season.

Age, serum 25-hydroxyvitamin D and vitamin D receptor (VDR) expression and function in peripheral blood mononuclear cells.

The relationship between age, vitamin D status, expression and functionality of the vitamin D receptor (VDR), and key genes in the vitamin D pathway in immune cells is unclear. We enrolled adults 50 to 69 years old (20 subjects) and 70+ (20 subjects) and measured: 1) 25(OH)D levels by liquid chromatography/mass spectrometry; and 2) mRNA expression of VDR, 1α-OHase, 1,25D3-MARRS, TREM-1, cathelicidin, RIG-I, and interferon-ß by qRT-PCR. Mean serum 25(OH)D was 30 ± 4 ng/mL and was not associated with age. Baseline expression of VDR, 1α-OHase, 1,25D3-MARRS, TREM-1, and RIG-I also did not differ by age; IFN-ß expression, however, was higher in the 70+ year old group. 25(OH)D3- and 1,25(OH)2D3-induced VDR, TREM-1 and cathelicidin expression were similar between age groups, as was LPS-induced expression of VDR and of 1α-OHase. Ligand-induced 1,25D3-MARRS expression was higher in subjects ≥ 70 years. Serum 25(OH)D was inversely associated with LPS-stimulated VDR expression and with baseline or vitamin D-induced TREM-1 expression, adjusting for age, self-rated health, and functional status. In healthy adults ≥ 50 years, the expression and functionality of the VDR, 1α-OHase and key vitamin D pathway genes were not consistently associated with age.

Measles Virus Neutralizing Antibody Response, Cell-Mediated Immunity, and Immunoglobulin G Antibody Avidity Before and After Receipt of a Third Dose of Measles, Mumps, and Rubella Vaccine in Young Adults.

BACKGROUND: Two doses of measles, mumps, and rubella (MMR) vaccine are 97% effective against measles, but waning antibody immunity to measles and failure of the 2-dose vaccine occur. We administered a third MMR dose (MMR3) to young adults and assessed immunogenicity over 1 year. METHODS: Measles virus (MeV) neutralizing antibody concentrations, cell-mediated immunity (CMI), and immunoglobulin G (IgG) antibody avidity were assessed at baseline and 1 month and 1 year after MMR3 receipt. RESULTS: Of 662 subjects at baseline, 1 (0.2%) was seronegative for MeV-neutralizing antibodies (level, <8 mIU/mL), and 23 (3.5%) had low antibody levels (8-120 mIU/mL). One month after MMR3 receipt, 1 subject (0.2%) was seronegative, and 6 (0.9%) had low neutralizing antibodies, with only 21 of 662 (3.2%) showing a ≥ 4-fold rise in neutralizing antibodies. One year after MMR3 receipt, no subject was seronegative, and 10 of 617 (1.6%) had low neutralizing antibody levels. CMI analyses showed low levels of spot-forming cells after stimulation, suggesting the presence of T-cell memory, but the response was minimal after MMR3 receipt. MeV IgG avidity did not correlate with findings of neutralization analyses. CONCLUSIONS: Most subjects were seropositive before MMR3 receipt, and very few had a secondary immune response after MMR3 receipt. Similarly, CMI and avidity analyses showed minimal qualitative improvements in immune response after MMR3 receipt. We did not find compelling data to support a routine third dose of MMR vaccine.

Preexisting Immunity, More Than Aging, Influences Influenza Vaccine Responses.

Background. Influenza disproportionately impacts older adults while current vaccines have reduced effectiveness in the older population. Methods. We conducted a comprehensive evaluation of cellular and humoral immune responses of adults aged 50 years and older to the 2008-2009 seasonal trivalent inactivated influenza vaccine and assessed factors influencing vaccine response. Results. Vaccination increased hemagglutination inhibition and neutralizing antibody; however, 66.3% of subjects did not reach hemagglutination inhibition titers ≥ 40 for H1N1, compared with 22.5% for H3N2. Increasing age had a minor negative impact on antibody responses, whereas prevaccination titers were the best predictors of postvaccination antibody levels. Preexisting memory B cells declined with age, especially for H3N2. However, older adults still demonstrated a significant increase in antigen-specific IgG(+) and IgA(+) memory B cells postvaccination. Despite reduced frequency of preexisting memory B cells associated with advanced age, fold-rise in memory B cell frequency in subjects 60+ was comparable to subjects age 50-59. Conclusions. Older adults mounted statistically significant humoral and cell-mediated immune responses, but many failed to reach hemagglutination inhibition titers ≥40, especially for H1N1. Although age had a modest negative effect on vaccine responses, prevaccination titers were the best predictor of postvaccination antibody levels, irrespective of age.

Comparison of Interviewer-Administered and Automated Self-Administered 24-Hour Dietary Recalls in 3 Diverse Integrated Health Systems.

Twenty-four-hour dietary recalls provide high-quality intake data but have been prohibitively expensive for large epidemiologic studies. This study's goal was to assess whether the web-based Automated Self-Administered 24-Hour Recall (ASA24) performs similarly enough to the standard interviewer-administered, Automated Multiple-Pass Method (AMPM) 24-hour dietary recall to be considered a viable alternative. In 2010-2011, 1,081 adults from 3 integrated health systems in Detroit, Michigan; Marshfield, Wisconsin; and Kaiser-Permanente Northern California participated in a field trial. A quota design ensured a diverse sample by sex, age, and race/ethnicity. Each participant was asked to complete 2 recalls and was randomly assigned to 1 of 4 protocols differing by type of recall and administration order. For energy, the mean intakes were 2,425 versus 2,374 kcal for men and 1,876 versus 1,906 kcal for women by AMPM and ASA24, respectively. Of 20 nutrients/food groups analyzed and controlling for false discovery rate, 87% were judged equivalent at the 20% bound. ASA24 was preferred over AMPM by 70% of the respondents. Attrition was lower in the ASA24/AMPM study group than in the AMPM/ASA24 group, and it was lower in the ASA24/ASA24 group than in the AMPM/AMPM group. ASA24 offers the potential to collect high-quality dietary intake information at low cost with less attrition.

Factors associated with maintenance of antibody responses to influenza vaccine in older, community-dwelling adults.

BACKGROUND: Little is known about factors associated with maintenance of hemagglutinin inhibition (HAI) antibodies after influenza vaccination in older adults. METHODS: Adults ≥50 years of age were vaccinated prior to the 2009-10 influenza season. Serum was drawn pre-vaccination (S1), 21-28 days post-vaccination (S2), and after the influenza season (S3) for HAI assays. Seroconversion was defined as ≥ 4-fold increase S1 to S2 (or if S1 < 10, by an S2 ≥ 40) and seroprotection was defined as S2 ≥ 40. Maintenance of antibody response was measured in participants with an S2 ≥ 40, and defined as an S3 ≥ 40. RESULTS: We enrolled 510 participants during Fall 2009 at Vanderbilt University Medical Center and Marshfield Clinic Research Foundation. Participants' mean age was 64 years with 62% female and 96% white. Seroconversion and seroprotection rates were lowest for influenza A H1N1 (12% and 26%, respectively), highest for influenza A H3N2 (45% and 82%), and intermediate for influenza B (28% and 72%). Of the participants with an S2 ≥ 40, 36% (46/126), 71% (289/407), and 74% (263/354) maintained an S3 ≥ 40 for H1N1, H3N2, and B influenza vaccine strains, respectively. S1 HAI titer was strongly associated with both post-vaccination seroprotection and maintaining seroprotection at S3 for all three influenza antigens. Age, sex, body mass index, self-reported stress, and vaccination site were not consistently associated with vaccine response or maintenance of response. CONCLUSIONS: Pre-vaccination antibody titer was the only study variable consistently and positively associated with both serologic response to vaccination and maintenance of response. Antibody responses were lowest for the H1N1 vaccine strain. CLINICALTRIALS: gov Identifier: NCT02401893.

Vitamin E, vitamin A, and zinc status are not related to serologic response to influenza vaccine in older adults: an observational prospective cohort study.

It has been hypothesized that micronutrient levels play a role in the immune response to vaccination; however, population-level research on the association between micronutrient levels and immune response to influenza vaccination is needed. In this study, we hypothesized that decreasing levels of nutrients would be associated with decreased hemagglutination inhibition (HAI) responses to influenza vaccination. Therefore, the purpose of this study was to determine whether serum vitamin A, vitamin E, or zinc levels are associated with influenza vaccine response determined by HAI titer in adults 65 years or older. Participants in this study included 205 community-dwelling adults 65 years or older who resided in Marshfield, WI, USA, from fall 2008 through spring 2009. Participants received trivalent influenza vaccine and donated blood samples before and 21 to 28 days after vaccination. Prevaccination levels of serum retinol, α-tocopherol, and zinc as well as prevaccination and postvaccination HAI titer levels were measured. No participants were vitamin A or vitamin E deficient; 20% had low serum zinc levels (<70 µg/dL). Continuous variables and categorical quartiles coding for vitamin A, vitamin E, and zinc levels were not related to prevaccination or postvaccination seroprotection or seroconversion for any of the vaccine components (influenza A [H1N1], A [H3N2], or B), after adjusting for age, sex, body mass index, and prevaccination HAI geometric mean titer. In conclusion, our study population showed no association between variations in levels of serum vitamin A, vitamin E, or zinc and influenza vaccine response as measured by HAI in adults older than 65 years. Thus, associations between micronutrients and other measures of vaccine response, such as cell-mediated immune parameters, should also be explored.

Mumps antibody response in young adults after a third dose of measles-mumps-rubella vaccine.

BACKGROUND: Mumps outbreaks in populations with high 2-dose measles-mumps-rubella (MMR) vaccine coverage raise the question whether a third dose of MMR vaccine (MMR3) is needed. However, data on the immunogenicity of MMR3 are limited. We assessed mumps virus neutralizing antibody levels pre- and post-MMR3 in a nonoutbreak setting. METHODS: Mumps antibody titers were assessed at baseline, 1 month, and 1 year after MMR3 in subjects aged 18-28 years. RESULTS: At baseline, 5 of 656 (0.8%) subjects had seronegative mumps neutralizing antibody titers and 38 (5.8%) had low titers. One year post-MMR3, these numbers declined to 3 (0.5%) and 16 (2.4%), respectively. Subjects with low baseline titers were more likely to have low 1-month and 1-year titers (R (2) = 0.81-0.87, P < .0001). Compared to baseline, geometric mean titers were significantly higher at 1 month (P < .0001) and 1 year (P < .01) post-MMR3; however, reverse cumulative distribution curves showed only minimal shifts in mumps titers from baseline to 1 month and 1 year. CONCLUSIONS: Very few subjects had negative or low baseline mumps titers. Nonetheless, mumps titers had modest but significant increases when measured 1 month and 1 year post-MMR3. This temporary increase in titers could decrease susceptibility to disease during outbreaks, but may have limited value for routine use in vaccinated populations.

Vitamin D is not associated with serologic response to influenza vaccine in adults over 50 years old.

Vitamin D deficiency has been implicated in risk of respiratory illness. We determined whether serum vitamin D levels are related to influenza vaccine response measured by hemagglutination antibody inhibition (HAI) titer in adults aged ≥50 years old. The study was a prospective cohort study conducted over two influenza seasons (fall 2008-spring 2009 and fall 2009-spring 2010) in Marshfield, WI and Nashville, TN including 1103 community-dwelling adult volunteers ≥50 years of age. Pre-vaccination levels of serum vitamin D and HAI titer levels pre- and 21-28 days post-influenza vaccination were measured. Seroprotection was defined as HAI ≥40; seroconversion was defined as ≥4-fold rise in HAI titers from pre- to post-vaccination. More than 25% of participants were vitamin D deficient (<25ng/mL). Vitamin D measured as a continuous variable was not related to pre- or post-vaccination seroprotection or seroconversion for any vaccine strain in any year. Vitamin D deficiency was associated with a greater frequency of post-vaccination seroprotection for seasonal H1N1 in the first year of the study, but was not related to seroprotection or seroconversion for any other strain in either year. No consistent association was found between vitamin D levels or vitamin D deficiency and serologic response to influenza vaccination in older adults. Cell-mediated immune parameters should also be explored in order to further investigate possible relationships between micronutrient status and influenza vaccine response.

Evaluation of obesity as an independent risk factor for medically attended laboratory-confirmed influenza.

BACKGROUND: The relationship between obesity and susceptibility to influenza infection in humans is unclear. Morbidly obese people were at an increased risk of complications from 2009 pandemic H1N1 influenza [A(H1N1)pdm09]. OBJECTIVE: The goal of this study was to determine whether medically attended, laboratory-confirmed influenza is independently associated with obesity in adults with acute respiratory illness. PATIENTS/METHODS: Adults ≥20 years with a medical encounter for acute respiratory illness were recruited from a population cohort during the 2007-2008 (n = 903), 2008-2009 (n = 869), and 2009 pandemic (n = 851) season. Nasopharyngeal swabs were tested for influenza by real-time reverse-transcription polymerase chain reaction. Body mass index (BMI) was calculated using data from the electronic medical record. Logistic regression evaluated the association between influenza and obesity, adjusting for gender, vaccination, age, and high-risk medical condition. RESULTS: Influenza was detected in 50% of patients in 2007-2008, 15% in 2008-2009, and 14% during the 2009 pandemic. Predominant seasonal viruses in this population were A/H3N2 in 2007-2008, and A/H1N1 and B in 2008-2009. Mean (±SD) BMI was 30·58 (±7·31) in patients with influenza and 30·93 (±7·55) in test-negative controls during all seasons. Mean BMI of patients with influenza did not vary by season. After adjusting for confounders, neither obesity nor extreme obesity were associated with influenza by season or for all years combined (OR 0·95: 95% CI 0·75, 1·20 and 1·10: 0·80, 1·52, respectively, for obesity and extreme obesity, all years). CONCLUSIONS: Obesity was not associated with medically attended influenza among adults with acute respiratory illness in this population.

Vitamin D and influenza.

Vitamin D has become increasingly recognized in the literature for its extra-skeletal roles, including an effect on inflammation and the immune response to infection. Our goal was to describe the role of vitamin D in the immune response and implications for the risk of influenza infection in humans. In this review, we first consider literature that provides molecular and genetic support to the idea that vitamin D is related to the adaptive and innate immune responses to influenza infection in vitro and in animal models. We then discuss observational studies and randomized controlled trials of vitamin D supplementation in humans. Finally, we consider some of the knowledge gaps surrounding vitamin D and immune response that must be filled.