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Objectives: Older adults are less able to produce a protective antibody response to vaccinations. One factor that contributes to this is immune ageing. Here we examined whether diurnal variations in immune responses might extend to the antibody response to vaccination., Design: We utilised a cluster-randomised trial design., Setting: 24 General Practices (GPs) across the West Midlands, UK who were assigned to morning (9-11am; 15 surgeries) or afternoon (3-5pm; 9 surgeries) vaccination times for the annual UK influenza vaccination programme., Participants: 276 adults (aged 65+ years and without a current infection or immune disorder or taking immunosuppressant medication)., Interventions: Participants were vaccinated in the morning or afternoon between 2011 and 2013., Main Outcome Measures: The primary outcome was the change in antibody titres to the three vaccine influenza strains from pre-vaccination to one month post-vaccination. Secondary outcomes of serum cytokines and steroid hormone concentrations were analysed at baseline to identify relationships with antibody responses., Results: The increase in antibody levels due to vaccination differed between morning and afternoon administration; mean difference (95% CI) for H1N1 A-strain, 293.3 (30.97-555.66) p=.03, B-strain, 15.89 (3.42-28.36) p=.01, but not H3N2 A-strain, 47.0 (-52.43 to 146.46) p=.35; those vaccinated in the morning had a greater antibody response. Cytokines and steroid hormones were not related to antibody responses. No adverse events were reported., Conclusions: This simple manipulation in the timing of vaccine administration to favour morning vaccination may be beneficial for the influenza antibody response in older adults, with potential implications for vaccination strategies generally., Trial Registration: This trial is registered with the ISRCTN (ISRCTN70898162)., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Elevated inflammatory levels are linked to poorer cognition, but experimental confirmation is lacking. This report examined associations between cognitive performance and inflammation induced by exercise and vaccination. Thirty-six (exercise N = 18, vaccination N = 18) healthy males completed a paced auditory serial addition test (PASAT), which is a multifaceted measure of cognitive function. The task was completed in placebo and elevated inflammation states. Improvements in PASAT performance were related to inflammation. In the exercise study, IL-6 during the first PASAT negatively correlated with PASAT improvement (p = .022). In the vaccination study, increases in C-reactive protein between PASATs correlated with reduced PASAT improvement (p < .001). Inflammation was linked to reduced improvements in cognitive performance. Further research should identify the specific cognitive functions affects and the underlying mechanisms., (© 2014 Society for Psychophysiological Research.)

Objective: To assess whether a life-style physical activity intervention improved antibody response to a pneumococcal vaccination in sedentary middle-aged women., Methods: Eighty-nine sedentary women completed a 16-week exercise (physical activity consultation, pedometer, telephone/e-mail prompts; n = 44) or control (advisory leaflet; n = 45) intervention. Pneumococcal vaccination was administered at 12 weeks, and antibody titers (11 of the 23 contained in the pneumococcal vaccine) were determined before vaccination and 4 weeks and 6 months later. Physical activity, aerobic fitness, body composition, and psychological factors were measured before and after the intervention., Results: The intervention group displayed a greater increase in walking behavior (from mean [standard deviation] = 82.16 [90.90] to 251.87 [202.13]) compared with the control condition (111.67 [94.64] to 165.16 [117.22]; time by group interaction: F(1,68) = 11.25, p = .001, η(2) = 0.14). Quality of life also improved in the intervention group (from 19.37 [3.22] to 16.70 [4.29]) compared with the control condition (19.97 [4.22] to 19.48 [5.37]; time by group interaction: F(1,66) = 4.44, p = .039, η(2) = 0.06). However, no significant effects of the intervention on antibody response were found (time by group η(2) for each of the 11 pneumococcal strains ranged from 0.001 to 0.018; p values all >.264)., Conclusions: Participation in a life-style physical activity intervention increased subjective and objective physical activity levels and quality of life but did not affect antibody response to pneumococcal vaccination.

The Salmonella typhi vaccination induces transient increases in inflammatory-responsive cytokines and molecules. For instance, it causes small, mild increases in interleukin-6 (IL-6) within a few hours and C-reactive protein (CRP) within 24h. No study has charted either the time course of the inflammatory response to this vaccine or any associated changes in mood, physical symptoms, and cardiac function. In a blinded crossover experimental design, eight participants received the S. typhi vaccine (vaccination condition) and a saline (control condition) injection on two separate days, at least one week apart. Blood samples and mood ratings were collected at 0, 4, 5, 6, 7, 8 and 24h post-injection, physical symptoms and pain were assessed at 4-8 and 24h post-injection, and cardiovascular function was recorded until 8h post-injection. Repeated measures analyses of variance and polynomial trend analyses compared the timecourse of the response patterns between the two conditions. Whereas there were no temporal changes in the control condition, the vaccination increased granulocytes, IL-6, TNF-α, and CRP (all p's<.05). Specifically, the granulocytes, IL-6 and TNF-α peaked after 6-8h while CRP peaked after 24h. This vaccine-induced mild inflammatory response was not accompanied by any changes in mood or cardiovascular activity. We also found that participants tended to report more pain in the injected limb in the vaccination condition (p<.07). In sum, our study charted the timecourse of key inflammatory-responsive markers following S. typhi vaccination and identified the timing of their modest peaks. It is worth noting that changes in these markers were not accompanied by any notable changes in mood or cardiovascular activity, and thus the S. typhi vaccination is a suitable method to induce increases in inflammatory-responsive markers, without altering mood or cardiovascular parameters., (Copyright © 2013 Elsevier Inc. All rights reserved.)

An acute bout of exercise prior to vaccination can improve the antibody and cell-mediated responses to influenza vaccination. The mechanisms underpinning this adjuvant effect remain unclear, and further investigation to determine the optimal exercise protocol is warranted. The aim of the current study was to determine whether exercise augmented the immune response to vaccination, and whether the timing of exercise relative to vaccination affected the efficacy of the intervention. One hundred and fifty-six (76 men) healthy participants were randomly assigned to a control group or one of three intervention groups who exercised immediately, 6h or 48 h prior to administration of a standard trivalent influenza vaccine. The exercise groups performed 50 repetitions of the eccentric portion of both the bicep curl and lateral raise movements at an intensity eliciting 85% of each participant's pre-determined concentric one repetition maxima. Antigen-specific serum antibody titres were measured at baseline and 28 days post-vaccination as indicators of the humoral response. All three viral strains elicited strong antibody responses; however, eccentric exercise did not further augment any antibody responses compared to the control group. Cell-mediated immunity at 28 days post-vaccination was determined by measuring the IFN-gamma response to in vitro stimulation of the blood with whole vaccine. There were no differences in cell-mediated immunity among the groups. Although these null findings were unexpected, they are consistent with previous research showing that exercise-induced immunoenhancement was only observed when the control group had relatively poor responses. In conclusion, it is likely that the robust immune responses to the vaccine observed in this study may have limited any further immune enhancement by exercise., (Copyright 2009 Elsevier Inc. All rights reserved.)

The importance of salivary SARS-CoV-2 antibodies, following infection and vaccination, has not been fully established. 875 healthcare workers were sampled during the first wave in 2020 and 66 longitudinally in response to Pfizer BioNTech 162b2 vaccination. We measured SARS-CoV-2 total IgGAM and individual IgG, IgA and IgM antibodies. IgGAM seroprevalence was 39.9%; however, only 34.1% of seropositive individuals also had salivary antibodies. Infection generated serum IgG antibodies in 51.4% and IgA antibodies in 34.1% of individuals. In contrast, the salivary antibody responses were dominated by IgA (30.9% and 12% generating IgA and IgG antibodies, respectively). Post 2nd vaccination dose, in serum, 100% of infection naïve individuals had IgG and 82.8% had IgA responses; in saliva, 65.5% exhibited IgG and 55.2% IgA antibodies. Prior infection enhanced the vaccine antibody response in serum but no such difference was observed in saliva. Strong neutralisation responses were seen for serum 6 months post 2nd-vaccination dose (median 87.1%) compared to low neutralisation responses in saliva (median 1%). Intramuscular vaccination induces significant serum antibodies and to a lesser extent, salivary antibodies; however, salivary antibodies are typically non-neutralising. This study provides further evidence for the need of mucosal vaccines to elicit nasopharyngeal/oral protection. Although saliva is an attractive non-invasive sero-surveillance tool, due to distinct differences between systemic and oral antibody responses, it cannot be used as a proxy for serum antibody measurement. • Largest investigation of SARS-CoV-2 serum and salivary antibodies in 875 healthcare workers. • In-depth profiling of combined anti-Spike IgGAM and individual immunoglobulin classes. • Saliva is not equivalent to serum. [ABSTRACT FROM AUTHOR]

Background: Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity. Objectives: To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency. Methods: Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, livevirus neutralisation and ELISPOT assays. Results: Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infectionnaive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%). Conclusion: These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency. [ABSTRACT FROM AUTHOR]

Bacteremia caused by nontyphoidal strains of Salmonella is endemic among African children. Case-fatality rates are high and antibiotic resistance increasing, but no vaccine is currently available. T cells are important for clearance of Salmonella infection within macrophages, but in Africa, invasive Salmonella disease usually manifests in the blood and affects children between 4 months and 2 y of age, when anti-Salmonella antibody is absent. We have previously found a role for complement-fixing bactericidal antibody in protecting these children. Here we show that opsonic activity of antibody and complement is required for oxidative burst and killing of Salmonella by blood cells in Africans. Induction of neutrophil oxidative burst correlated with anti-Salmonella lgG and 1gM titers and C3 deposition on bacteria and was significantly lower in African children younger than 2 y compared with older children. Preopsonizing Salmonella with immune serum overcame this deficit, indicating a requirement for antibody and/or complement. Using different opsonization procedures, both antibody and complement were found to be necessary for optimal oxidative burst, phagocytosis and killing of nontyphoidal Salmonella by peripheral blood cells in Africans. Although most strains of African nontyphoidal Salmonella can be killed with antibody and complement alone, phagocytes in the presence of specific antibody and complement can kill strains resistant to killing by immune serum. These findings increase the likelihood that an antibody-inducing vaccine will protect against invasive nontyphoidal Salmonella disease in African children. [ABSTRACT FROM AUTHOR]

Abstract: Acute exercise at the time of vaccination can enhance subsequent immune responses. However, the potential benefit of this effect will be its efficacy in boosting poor responses, and thus protection in at-risk populations. The current study tested the effect of exercise on the response to either a full- or half-dose Pneumococcal (Pn) vaccination to elicit stronger and weaker responses. Subjects were 133 young healthy adults, randomised to one of four groups: exercise or control task, receiving a full- or half-dose Pn vaccination. Prior to vaccination, exercise groups completed a 15min arm and shoulder exercise task, control groups rested quietly. Antibody levels to 11 Pn strains were evaluated at baseline and 1-month. Across all participants, exercise groups showed significantly greater increase in antibody levels than control groups. When doses were compared, it emerged that those who exercised had significantly larger responses than those who rested in the half-dose group, but in the full-dose groups responses were similar. This data indicates the effectiveness of exercise as a vaccine adjuvant, particularly in weaker responses. Thus, given the potential public health benefits of no-cost behavioural intervention to enhance response to vaccination, testing in at-risk populations should be pursued. [Copyright &y& Elsevier]

Abstract: The measurement of antibody responses to vaccination is useful in the assessment of immune status in suspected immune deficiency. Previous reliance on enzyme-linked immunoabsorbent assays (ELISA) has been cumbersome, time-consuming and expensive. The availability of flow cytometry systems has led to the development of multiplexed assays enabling simultaneous measurement of antibodies to several antigens. We optimized a flow cytometric bead-based assay to measure IgG and IgM concentrations in serum to 19 antigens contained in groups of bacterial subunit vaccines: pneumococcal vaccines, meningococcal vaccines, Haemophilus influenzae b (Hib), and tetanus and diphtheria toxoid vaccines. 89-SF was employed as the standard serum. The assay was used to determine specific antibody levels in serum from 193 healthy adult donors. IgG and pneumococcal IgM antibody concentrations were measurable across 3 log10 ranges encompassing the threshold protective IgG antibody levels for each antigen. There was little interference between antibody measurements by the 19-plexed assay compared with monoplexed assays, and a lack of cross-reactive IgG antibody, but evidence for cross-reacting IgM antibody for 3/19 pneumococcal antigens. 90th centile values for 15/19 IgG concentrations and 12/12 IgM concentrations of the 193 adult sera were within these ranges and percentages of sera containing protective IgG antibody levels varied from 4% to 95% depending on antigen. This multiplexed assay can simultaneously measure antibody levels to 19 bacterial vaccine antigens. It is suitable for use in standard clinical practice to assess the in vivo immune response to test vaccinations and measure absolute antibody levels to these antigens. [Copyright &y& Elsevier]

Abstract: Acute exercise prior to vaccination can improve the antibody response to influenza vaccination. However, both the optimal exercise protocol and the mechanisms underpinning this adjuvant effect remain unclear. The aim of the current study was to determine whether exercise intensity influenced the efficacy of the intervention. One hundred and sixty healthy young adults were randomly assigned to a resting control group or one of three intervention groups, who exercised at an intensity of 60%, 85%, or 110% of their pre-determined concentric one repetition maxima. The exercise groups performed 50 repetitions of the eccentric portion of both bicep curl and lateral raise movements. All participants then immediately received a reduced dose (50% recommended dose) influenza vaccine. Antibody titres to the three viral strains contained in the vaccine were measured at baseline and at 28days post-vaccination. Compared to the control group, exercise enhanced the antibody response to the least immunogenic of the three strains (B/Florida). In addition, the exercise groups showed an augmented response to the A/Uruguay strain compared to control; however, this effect was observed only in men. The intervention had no effect on the antibody responses to the most immunogenic strain, A/Brisbane. Finally, antibody responses were unrelated to the intensity of the exercise bout. In conclusion, our findings provide further evidence of exercise as an adjuvant to enhance vaccination responses. The results further show that responses to the low-immunogenic antigens are particularly responsive to augmentation by acute eccentric exercise. [Copyright &y& Elsevier]

Abstract: The present study examined the association between psychological stress, social support and antibody response to both thymus-dependent and thymus-independent vaccinations. Stressful life events in the previous year and customary social support were measured by standard questionnaires at baseline in 75 (41 females) healthy students. Antibody status was assessed at baseline, 4 and 18 weeks following vaccination with formaldehyde inactivated hepatitis A virus and pneumococcal polysaccharides, which induce thymus-dependent and -independent antibody responses respectively. Controlling for baseline antibody status, life event stress was negatively associated with antibody response to the hepatitis A vaccine at the 18-week follow-up; participants reporting a greater number of stressful life events had a poorer antibody response. There was no relationship between psychological stress and antibody response to pneumococcal vaccination. Social support was not associated with the antibody response to hepatitis A vaccination. However, there was a significant association between support and the antibody response to the thymus-independent pneumococcal vaccine at 4-week follow-up; participants with larger social networks mounted a better response. These relationships could not be accounted for by age and sex, or by variations in health behaviours. Psychosocial factors would appear to influence the response to both thymus-dependent and thymus-independent vaccines, but not in the same manner. [Copyright &y& Elsevier]