Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation – A single center retrospective efficacy analysis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6–70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients’ characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p < 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.     

Determinants of Bacillus Calmette–Guérin (BCG) vaccination among Québec children

ObjectivesTo identify determinants of Bacillus Calmette–Guérin (BCG) vaccination among children born in Québec, Canada, in 1974, the last year of the systematic vaccination campaign.MethodA retrospective birth cohort was assembled in 2011 through probabilistic linkage of administrative databases (n = 81,496). Potential determinants were documented from administrative databases and by interviewing a subset of subjects (n = 1643) in 2012. Analyses were conducted among subjects with complete data, 71,658 (88%) birth cohort subjects and 1154 (70%) interviewed subjects, then redone using multiple imputation. Determinants of BCG vaccination during the organized vaccination program (in 1974), and after the program (1975 onwards) were assessed separately. Logistic regression with backward elimination was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsOverall, 46% of subjects were BCG vaccinated, 43% during the program and 4% after it ended. BCG vaccination during the program was associated with parents' birthplace and urban or rural residence. BCG vaccination after the organized program was only related to ethnocultural origin of the child's grandparents.ConclusionDifferent factors were related to vaccination within and after the organized program. Determinants of BCG vaccination in Québec, Canada, have never been studied and will be useful for future research and vaccination campaigns.     

Neonatal Bacille Calmette-Guérin vaccination and tuberculin skin test reactions at 2- and 6-months: Effects on mortality up to 1 year of age

BackgroundIn randomized trials, Bacille Calmette-Guérin (BCG) vaccine has been associated with reduced all-cause mortality. BCG-induced Tuberculin Skin Test (TST) reactions have also been associated with reduced all-cause mortality. We aimed to assess the association between TST responses and subsequent mortality in three birth cohorts and conducted a meta-analysis of existing studies.MethodsObservational study within three Guinea-Bissau BCG trial birth cohorts (conducted 2002–04, 2009–2013 and 2014–18) that encompassed children who were BCG-vaccinated within 28 days with TSTs performed at 2- (n = 1389) and 6-months (n = 2635) of age. We evaluated TST reaction determinants by binomial regression and assessed the association between TSTs > 1 mm (reactors) vs. ≤ 1 mm (non-reactors) and subsequent mortality risk up to age 12 months in Cox-models providing Mortality Rate Ratios (MRRs). We searched PubMed for studies to calculate meta-estimates of the association between TST reactivity by age 2- and 6-months and all-cause mortality.ResultsLarge post-vaccination wheal size was associated with 6-month TST positivity and so was receiving BCG-Denmark or BCG-Japan, compared with BCG-Russia. By age 2 months, 22% (302/1389) of infants were TST reactors with a 2–12-month mortality risk of 1.7% (5/302) vs. 3.3% (36/1087) for non-reactors, the corresponding reactor/non-reactor MRR = 0.49 (0.19–1.26). By age 6 months, 44% (1149/2635) of infants were reactors and the 6–12-month mortality risk was 0.4% (4/1149) vs. 0.6% (9/1486) for non-reactors, the MRR = 0.87 (0.27–2.86). The literature search provided 3 studies. The meta-analysis revealed a uniform pattern of reduced mortality associated with TST reactivity, a TST response by 2 months being associated with an MRR of 0.59 (0.39–0.90); for 6-month TST responses the MRR was 0.65 (0.43–1.00).ConclusionAmong BCG-vaccinated infants, TST reactions were associated with markedly reduced mortality. Improved vaccination technique and using certain BCG strains could lead to a higher TST reaction prevalence, which would enhance BCG’s beneficial non-specific effects.     

Bacille Calmette-Guérin vaccination at birth and differential white blood cell count in infancy. A randomised clinical trial

BackgroundThe Bacille Calmette-Guérin (BCG) vaccine against tuberculosis (TB) may have beneficial non-specific effects (NSEs) beyond the protection against TB. This may be related to modifications of the innate immune system. We investigated the effect of BCG at birth on differential white blood cell (WBC) count in healthy, Danish infants.MethodThe Danish Calmette Study randomised newborns to BCG at birth (Danish strain 1331, Statens Serum Institut) or no intervention. A sub-group of infants had blood samples collected 4 days after randomisation (n = 161), and at age 3 months (n = 152) and 13 months (n = 300). We evaluated the effect of BCG on WBC differential count (total leucocytes, lymphocytes, monocytes, eosinophil, neutrophil and basophil granulocytes (10⁹ cells/L)) measured in peripheral blood.ResultsOverall, we found no effect of BCG on differential WBC counts at any time point.ConclusionBCG at birth did not affect WBC count in our cohort of healthy, Danish infants.     

Delayed BCG vaccination results in minimal alterations in T cell immunogenicity of acellular pertussis and tetanus immunizations in HIV-exposed infants

BackgroundBacille Calmette–Guerin (BCG) is effective in preventing disseminated tuberculosis (TB) in children but may also have non-specific benefits, and is thought to improve immunity to unrelated antigens through trained innate immunity. In HIV-infected infants, there is a risk of BCG-associated adverse events. We aimed to explore whether delaying BCG vaccination by 8 weeks, in utero or perinatal HIV infection is excluded, affected T-cell responses to B. pertussis (BP) and tetanus toxoid (TT), in HIV-exposed, uninfected infants.MethodsInfants were randomized to receive BCG vaccination at birth or 8 weeks of age. At 8 and 14 weeks, T cell proliferation and intracellular cytokine (IL-2, IL-13, IL-17, and IFN-γ) expression was analyzed in response to BP, TT and Staphylococcal enterotoxin B (SEB) antigens.ResultsDelaying BCG vaccination did not alter T-cell proliferation to BP or TT antigens. Infants immunized with BCG at birth had higher CD4+ T cell proliferation to SEB at 14 weeks of age (p = 0.018). Birth-vaccinated infants had increased CD8+ IL-2 expression in response to BP, but not TT or SEB, at 8 weeks. Infants vaccinated with BCG at 8 weeks had significantly lower IL-13 expression by BP-specific CD4+ and CD8+ T cells at 14 weeks (p = 0.032 and p = 0.0035, respectively). There were no observed differences in multifunctional cytokine response to TT, BP or SEB between infants vaccinated with BCG at birth versus 8 weeks of age.ConclusionDelaying BCG vaccination until 8 weeks of age results in robust T-cellular responses to BP and TT in HIV-exposed infants.Clinical Trial Registry: NCT02062580.     

Delaying BCG vaccination from birth to 10 weeks of age may result in an enhanced memory CD4 T cell response

Background

In most tuberculosis (TB) endemic countries, bacillus Calmette–Guérin (BCG) is usually given around birth to prevent severe TB in infants. The neonatal immune system is immature. Our hypothesis was that delaying BCG vaccination from birth to 10 weeks of age would enhance the vaccine-induced immune response.

Methods

In a randomized clinical trial, BCG was administered intradermally either at birth (n = 25) or at 10 weeks of age (n = 21). Ten weeks after vaccination, and at 1 year of age, vaccine-specific CD4 and CD8 T cell responses were measured with a whole blood intracellular cytokine assay.

Results

Infants who received delayed BCG vaccination demonstrated higher frequencies of BCG-specific CD4 T cells, particularly polyfunctional T cells co-expressing IFN-γ, TNF-α and IL-2, and most strikingly at 1 year of age.

Conclusions

Delaying BCG vaccination from birth to 10 weeks of age enhances the quantitative and qualitative BCG-specific T cell response, when measured at 1 year of age.     

The association between parental and neonatal BCG vaccination and neonatal T helper 17 cell expansion

BackgroundBacille Calmette-Guérin (BCG) vaccination reduces the severity of neonatal infections; this effect appears enhanced if the mother has received BCG. We performed immunophenotyping of the T-cell subset and characterized T-cell proliferation responses to assess possible immune response pathways.MethodsHealthy BCG-vaccinated (n = 8) and unvaccinated (n = 9) neonates born by elective caesarean section were sampled 3 weeks after birth. We compared a wide panel of intracellular cytokine and cell surface expression markers as well as proliferation response in T-cells between BCG-vaccinated and unvaccinated neonates, stratified by parental BCG status.ResultsFor all BCG-vaccinated neonates and 3 of 9 unvaccinated neonates that served as controls, both parents had a BCG scar. Th17 (CD4 + IL-17+) prevalence as percentage of total CD4 + T-cells was expanded 4-fold in BCG-vaccinated compared to unvaccinated, being 11.6% [3.6–19.6%] vs 2.8% [1.0–6.6%]. Th17 counts for 3 unvaccinated neonates born to BCG-vaccinated parents was comparable to vaccinated neonates, and higher than remaining controls, parental BCG = 8.5% [4.4–8.9%] vs 1.8% [0.8–3.3%] for no parental BCG (median [interquartile range] for all data).ConclusionAmong neonates born to BCG-vaccinated parents, the prevalence of Th17 cells, important in the response against bacterial infections, was substantially elevated. The interaction between neonatal and parental BCG for Th17 responses and the importance remains to be further investigated.     

Immunogenicity and safety of hepatitis B vaccination in patients with type 2 diabetes in China: An open-label randomized controlled trial

ObjectiveHepatitis B virus (HBV) infection remains a global public health challenge. Patients with diabetes are at greater risk of HBV infection than healthy people. The immunogenicity and safety of two major hepatitis B vaccines were evaluated in Chinese patients with diabetes.MethodsIn this phase IV, open-label, randomized, controlled study, participants with diabetes were randomly recruited from 6 township health centers in Gansu Province and received either a 3-dose Saccharomyces cerevisiae recombinant hepatitis B vaccine (Group D20SC 0-1-6, n = 113) or a 3-dose Chinese hamster ovary cell (CHO) recombinant hepatitis B vaccine (Group D20CHO 0-1-6, n = 119). Healthy control groups were randomly recruited from the same 6 health centers and received 3 doses of the saccharomyces cerevisiae recombinant hepatitis B vaccine (Group ND20SC 0-1-6, n = 77). Immunogenicity, including seroconversion rate and geometric mean concentration (GMC) at 1 month after three doses of vaccination, and safety were assessed. The seroconversion rate was defined as the concentration of HBsAb ≥ 10 mIU/mL.ResultsThe seroconversion rates of Group D20SC 0-1-6, Group D20CHO 0-1-6 and Group ND20SC 0-1-6 were 89.6%, 91.4% and 97.1%, respectively, in the per-protocol analysis, and these differences were not statistically significant. The antibody concentration in Group D20SC 0-1-6 (GMC = 601 mIU/mL) was lower than that of the healthy control group (GMC = 1465 mIU/mL), but no significant difference was found in the GMC between the Group D20CHO 0-1-6 (GMC = 778 mIU/mL) and Group D20SC 0-1-6. Adverse events (AEs) were comparable between groups, and no serious AEs were found in these three groups.ConclusionsThe Saccharomyces cerevisiae recombinant and CHO recombinant hepatitis B vaccines in China can induce good immunogenicity in a diabetic population, although the antibody concentration may be lower, indicating the feasibility of vaccinating a large number of diabetic patients in China with these vaccines.     

Epigenetic changes related to glucose metabolism in type 1 diabetes after BCG vaccinations: A vital role for KDM2B

BackgroundA recent epigenome-wide association study of genes associated with type 2 diabetics (T2D), used integrative cross-omics analysis to identify 22 abnormally methylated CpG sites associated with insulin and glucose metabolism. Here, in this epigenetic analysis we preliminarily determine whether the same CpG sites identified in T2D also apply to type 1 diabetes (T1D). We then determine whether BCG vaccination could correct the abnormal methylation patterns, considering that the two diseases share metabolic derangements.MethodsT1D (n = 13) and control (n = 8) subjects were studied at baseline and then T1D subjects studied yearly for 3 years after receiving BCG vaccinations in a clinical trial. In this biomarker analysis, methylation patterns were evaluated on CD4+ T-lymphocytes from baseline and yearly blood samples using the human Illumina Methylation EPIC Bead Chip. Methylation analysis combined with mRNA analysis using RNAseq.ResultsBroad but not complete overlap was observed between T1D and T2D in CpG sites with abnormal methylation. And in the three-year observation period after BCG vaccinations, the majority of the abnormal methylation sites were corrected in vivo. Genes of particular interest were related to oxidative phosphorylation (CPT1A, LETM1, ABCG1), to the histone lysine demethylase gene (KDM2B), and mTOR signaling through the DDIT4 gene. The highlighted CpG sites for both KDM2B and DDIT4 genes were hypomethylated at baseline compared to controls; BCG vaccination corrected the defect by hypermethylation.ConclusionsGlycolysis is regulated by methylation of genes. This study unexpectedly identified both KDM2B and DDIT4 as genes controlling BCG-driven re-methylation of histones, and the activation of the mTOR pathway for facilitated glucose transport respectively. The BCG effect at the gene level was confirmed by reciprocal mRNA changes. The DDIT4 gene with known inhibitory role of mTOR was re-methylated after BCG, a step likely to allow improved glucose transport. BCGs driven methylation of KDM2B’s site should halt augmented histone activity, a step known to allow cytokine activation and increased glycolysis.     

Cholecalciferol supplementation to improve the hepatitis B vaccination response in hemodialysis patients: A first randomized open label pilot study (DeVitaHep)

BackgroundPatients with advanced chronic kidney disease should be vaccinated against hepatitis B. In observational studies vitamin D insufficiency is associated with a reduced seroconversion rate. The effect of cholecalciferol supplementation on hepatitis B vaccination response in haemodialysis patients with vitamin D insufficiency is unknown.MethodsIn this randomized open label pilot study 40 unvaccinated haemodialysis patients with 25(OH)D insufficiency (<30 ng/mL) were enrolled. In the supplementation group, we administered cholecalciferol orally in a dose of 28,000 IU weekly for a maximum of 12 weeks. Hepatitis B vaccination (HBvaxPRO 40 µg i.m. months 0, 1, 6) was performed after achieving a 25(OH)D level >30 ng/mL or after completing three months of supplementation despite failure to achieve the target level. In the control group, patients were vaccinated immediately after randomization. Anti-hepatitis B-antibody titer (anti-HBs) was measured eight weeks after completing the vaccination course.ResultsThirty-seven (26 male, 11 female) patients aged 65 (13.5) years underwent randomization with 17 patients allocated to the control group and 20 patients included in the supplementation group. After 12 weeks of cholecalciferol supplementation, mean (SD) 25(OH)D concentration increased from 15.0 (8.0) to 31.0 (7.1) ng/mL, but remained unchanged in the control group (14.0 (7.1) to 11.6 (7.5) mg/mL). Neither the number of patients with seroconversion (anti-HBs titer ≥ 10 IU/L; n = 6 (35.3%) vs n = 3 (27.3%), p = 0.704), nor the number of patients with seroprotection (anti-HBs titer >100 IU/L; n = 4 (23.5%) vs n = 2 (18.2%) differed between treatment groups. Cholecalciferol supplementation was safe without treatment-related adverse events.ConclusionIn this small pilot study, high-dose oral cholecalciferol supplementation did not improve the hepatitis B vaccination response in haemodialysis patients with vitamin D insufficiency.This clinical trial was registered within EudraCT (EudraCT number 2011-004621-26).     

Women who received varicella vaccine versus natural infection have different long-term T cell immunity but similar antibody levels

BackgroundVaricella-zoster virus (VZV) infection during pregnancy is associated with serious fetal anomalies. The live-attenuated VZV vaccine was approved in 1995, so many vaccinated women are now of childbearing age. The question of long-term immunity to varicella is critical because breakthrough chickenpox can occur after vaccination.ObjectiveTo compare humoral and T cell immunity between women of childbearing age who were immunized by vaccination or chickenpox disease.Study designNon-pregnant females between 18 and 36 years old with a history of VZV immunization (n = 20) or prior chickenpox disease (n = 20) were recruited. IgG antibody titers and T cell responses were measured by flow cytometry-based methods in serum and peripheral blood, respectively.ResultsThere were no significant differences in median antibody titers between vaccinated and chickenpox groups (p = 0.34). The chickenpox group had significantly higher levels of VZV antigen-specific CD4 T cells (p = 0.004).ConclusionNatural infection induced higher VZV-specific T cell immune responses than vaccination.     

COVID-19 vaccination coverage in patients with chronic obstructive pulmonary disease – A cross-sectional study in Hungary

IntroductionCoronavirus infection is a particular risk for patients with chronic obstructive pulmonary disease (COPD), because they are much more likely to become severely ill due to oxygen supply problems. Primary prevention, including COVID-19 vaccination is of paramount importance in this disease group. The aim of our study was to assess COVID-19 vaccination coverage in COPD patients during the first vaccination campaign of the COVID-19 pandemic.MethodsA cross-sectional observational study (CHANCE) has been conducted in COPD patients in the eastern, western and central regions of Hungary from 15th November 2021. The anthropometric, respiratory function test results and vaccination status of 1,511 randomly selected patients were recorded who were aged 35 years and older.ResultsThe median age was 67 (61–72) years, for men: 67 (62–73) and for women: 66 (60–72) years, with 47.98 % men and 52.02 % women in our sample. The prevalence of vaccination coverage for the first COVID-19 vaccine dose was 88.62 %, whereas 86.57 % of the patients received the second vaccine dose. When unvaccinated (n = 172) and double vaccinated (n = 1308) patients were compared, the difference was significant both in quality of life (CAT: 17 (12–23) vs 14 (10–19); p < 0.001) and severity of dyspnea (mMRC: 2 (2–2) vs 2 (1–2); p = 0.048). The COVID-19 infection rate between double vaccinated and unvaccinated patients was 1.61 % vs 22.67 %; p < 0.001 six months after vaccination. The difference between unvaccinated and vaccinated patients was significant (8.14 % vs 0.08 %; p < 0.001) among those with acute COVID-19 infection hospitalized. In terms of post-COVID symptoms, single or double vaccinated patients had significantly fewer outpatient hospital admissions than unvaccinated patients (7.56 vs 0 %; p < 0.001).ConclusionThe COVID-19 vaccination coverage was satisfactory in our sample. The uptake of COVID-19 vaccines by patients with COPD is of utmost importance because they are much more likely to develop severe complications.     

Previous biological therapy and impairment of the IFN-γ/IL-10 axis are associated with low immune response to 17DD-YF vaccination in patients with spondyloarthritis

Yellow fever (YF) vaccination is known to induce a suboptimal response in patients with autoimmune diseases (AIDs). To date, few studies have focused on the performance of 17DD-YF vaccination in patients with spondyloarthritis (SpA). In general, patients with SpA are young and have less comorbidities than other patients with AIDs, and frequently receive biological disease-modifying antirheumatic drugs (DMARDs) that may impact their response to vaccines. Taking this background information, the present study aimed to investigate whether the use of biological DMARDs, even after planned washout, or disease activity measured by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), would impact the overall performance of planned 17DD-YF primary vaccination in patients with SpA. For this purpose, 74 subjects were enrolled in a prospective study, including adult patients with SpA (SpA; n = 51) and a healthy control (HC; n = 23) group. Analysis of YF specific neutralizing antibodies test (PRNT), along with YF viremia and the levels of serum chemokines, cytokines, and growth factors were performed at distinct time points (D0, D3, D4, D5, D6, D7, D14, and D28). The BASDAI scores were evaluated at D0 and D180. Data demonstrated that overall, the SpA group presented lower PRNT titers and seropositivity rates as compared to the HC group (GeoMean = 112 vs. 440; 73% vs. 96%, respectively). In SpA subgroup analyses, previous biological DMARDs (BIO-IT) led to a lower PRNT titers (BIO-IT 79, 95% CI [39–150] vs. without biological DMARDs [non-BIO-IT] 159, 95% CI [94–267], p < 0.001). The non-BIO-IT group achieved a response similar to the HC group (81% vs. 96%, p = 0.112), whereas the BIO-IT group had a lower seroconversion rate (64% vs. 96% HC, p = 0.007). The BASDAI was not associated with PRNT levels and did not change after 6 months of follow-up. No differences in YF viremia were observed amongst subgroups. Higher baseline levels of serum biomarkers were observed in the BIO-IT group vs. the non-BIO-IT group, as well as in those with a BASDAI ≥ 4 vs. those with a BASDAI < 4. Increasing levels of several biomarkers were observed in SpA, especially in the BIO-IT and BASDAI ≥ 4 subgroups throughout the timeline kinetics, with impairment/disturbance in the IFN-γ/IL-10 axis around the peak of viremia (D5). Altogether, these findings suggested that the use of biological DMARDs impacts the response to the 17DD-YF vaccine, even after planned washout. Therefore, previous biological DMARD therapy, the inflammatory status prior vaccination, and impairment of the IFN-γ/IL-10 axis at the peak of viremia may determine the immunogenicity of 17DD-YF vaccination in patients with SpA.     

Varicella-zoster-virus vaccination of immunosuppressed children with inflammatory bowel disease or autoimmune hepatitis: A prospective observational study

Background and aimsChildren with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) receiving immunosuppressive treatment are at risk for severe varicella zoster virus (VZV)-induced disease. This study evaluated vaccination of susceptible patients with stable disease and documented immunoreactivity without interruption of their current immunosuppression (IS).MethodsThis prospective multicentre observational study used a prevaccination checklist to select patients with low-intensity and high-intensity IS for VZV vaccination. Tolerability and safety after immunization were assessed by questionnaire. The immune response was measured by the VZV-IgG concentration, relative avidity index (RAI), and specific lymphocyte proliferative response.ResultsA total of 29 VZV vaccinations were performed in 17 seronegative patients aged 3–16 years (IBD n = 15, AIH n = 2). Eight patients received high-intensity immunosuppression, another six low-intensity immunosuppression, and three patients interrupted IS before VZV vaccination.All 29 vaccinations were well tolerated; only minor side effects such as fever and abdominal pain, were reported in two patients. One patient experienced a flare of Crohn’s disease the day after vaccination.The VZV-IgG-concentration increased significantly (p = 0.018) after vaccination, and a specific lymphocyte response towards VZV in vitro was detected in all tested patients which correlated with the RAI (r = 0.489; p = 0.078).ConclusionsVZV vaccination was well tolerated, safe and immunogenic in children receiving ongoing IS due to IBD and AIH. Ensuring immunoreactivity by clinical and laboratory parameters, rather than the type and dosage of IS, is a reasonable approach to decide on live-attenuated virus vaccinations in immunosuppressed children (German clinical trials DRKS00016357).     

Complementary medicine use and flu vaccination – A nationally representative survey of US adults

BackgroundPrior research presented inconsistent results with less, equal or higher vaccination rates among patients using complementary medicine. Given that complementary medicine includes a wide range of therapies, variable vaccination patterns may occur within consultations with different professions. This analysis aims to to evaluate differences between categories of complementary medicine regarding vaccination behavior among US adults.Methods and resultsThis analysis used data from the 2017 National Health Interview Survey (NHIS; n = 26,742; response rate 80.7%). Prevalences of flu vaccination, consultations with complementary medicine practitioners in the past 12 months and their potential interactions were examined. 42.7% of participants had received flu vaccination in the past 12 months, 32.4% had seen one or more complementary medicine practitioner. Users of any type of complementary medicine were as likely as non-users to have received a flu vaccination (44.8% users versus 41.7% non-users; p = 0,862; adjusted odds ratio [AOR] = 1.01, 95% confidence interval [CI] = 0.95–1.07). Regarding specific complementary medicine types, individuals consulting with naturopaths (p < 0.001; AOR = 0.67, 95 %CI = 0.54–0.82), homeopaths (p < 0.001; AOR = 0.55; 95 %CI = 0.44–0.69) and chiropractors (p = 0.016; AOR = 0.9, 95 %CI = 0.83–0.98) were less likely, while other complementary medicine approaches showed no significant association with flu vaccination behavior. Independent predictors for a flu shot were prior diabetes, cancer, current asthma, kidney disease, overweight and current pregnancy. As well, higher educational level, age, ethnicity, health insurance coverage and having seen a general physician or medical specialist in the past 12 months were also associated with a higher vaccination rate.ConclusionsComplementary medicine users were equally likely to receive an influenza vaccination compared with non-users. Different complementary therapies showed varied associations with vaccination behavior. Further analyses may be needed to distinguish influencing factors among patients’ vaccination behavior.     

Oropharyngeal shedding of herpesviruses before and after BNT162b2 mRNA vaccination against COVID-19

IntroductionConcerns were raised over an increase in Bell's palsy, herpes simplex and herpes zoster after BNT162b2 vaccination, all are manifestations of herpesviruses reactivation. As herpesviruses commonly reactivate in the oropharynx, we have hypothesized that oropharyngeal shedding of herpesviruses will increase after vaccination.MethodsImmune-competent Adults, excluding those using topical steroids or manifesting symptomatic herpesvirus infection, were sampled before BNT162b2 vaccination and one week after. Herpesviruses 1–7 shedding was tested with a multiplexed PCR.ResultsIn 103 paired samples the prevalence of herpesviruses was similar before and after vaccination: HSV1, 3.9% vs. 5.8% (p = 0.75); HSV2, 0% vs. 1% (p = not applicable, NA); VZV, 0% vs. 0% (p = NA); EBV, 14.6% vs. 17.5% (p = 0.63); CMV, 0% vs. 0% (p = NA); HHV6, 4.9% vs. 7.8% (p = 0.55); HHV7, 71.8% vs. 72.8% (p = 1); any herpesvirus, 73.8% vs. 74.8% (p = 1).DiscussionWe did not find evidence for increased oropharyngeal reactivation of herpesviruses one week after BNT162b2.     

Factors associated with repeated influenza vaccine uptake among aged care staff in an Australian sample from 2017 to 2019

Background/AimInfluenza vaccination is strongly recommended every year for aged care staff to protect themselves and minimise risk of transmission to residents. This study aimed to determine the factors associated with repeated annual influenza vaccine uptake among Australian aged care staff from 2017 to 2019.MethodsDemographic, medical and vaccination data collected from the staff, who participated in an observational study from nine aged care facilities under a single provider in Sydney Australia, were analysed retrospectively. Based on the pattern of repeated influenza vaccination from 2017 to 2019, three groups were identified: (1) unvaccinated all three years; (2) vaccinated occasionally(once or twice) over three years; and (3)vaccinated all three years. Multinomial logistic regression analysis was performed to better understand the factors associated with the pattern of repeated influenza vaccination.ResultsFrom a total of 138 staff, between 2017 and 2019, 28.9 % (n = 40) never had a vaccination, while 44.2 % (n = 61) had vaccination occasionally and 26.8 % (n = 37) had vaccination all three years. In the multinomial logistic regression model, those who were<40 years old (OR = 0.57, 95 % CI: 0.19–0.90, p < 0.05) and those who were current smokers (OR = 0.20; 95 % CI: 0.03–0.76, p < 0.05) were less likely to have repeated vaccination for all three years compared to the unvaccinated group. Those who were<40 years old (OR = 0.61; 95 % CI: 0.22–0.68, p < 0.05) and those who were born overseas (OR = 0.50; 95 % CI:0.27–0.69, p < 0.05) were more likely to be vaccinated occasionally compared to the unvaccinated group.ConclusionThe significant predictors of repeated vaccine uptake across the three-year study period among aged care staff were age, smoking status and country of birth (Other vs Australia). Targeted interventions towards the younger age group (<40 years old), smokers and those who were born overseas could improve repeated influenza vaccination uptake in the aged care workforce.     

A systems map of the economic considerations for vaccination: Application to hard-to-reach populations

BackgroundUnderstanding the economics of vaccination is essential to developing immunization strategies that can be employed successfully with limited resources, especially when vaccinating populations that are hard-to-reach.MethodsBased on the input from interviews with 24 global experts on immunization economics, we developed a systems map of the mechanisms (i.e., necessary steps or components) involved in vaccination, and associated costs and benefits, focused at the service delivery level. We used this to identify the mechanisms that may be different for hard-to-reach populations.ResultsThe systems map shows different mechanisms that determine whether a person may or may not get vaccinated and the potential health and economic impacts of doing so. The map is divided into two parts: 1) the costs of vaccination, representing each of the mechanisms involved in getting vaccinated (n = 23 vaccination mechanisms), their associated direct vaccination costs (n = 18 vaccination costs), and opportunity costs (n = 5 opportunity costs), 2) the impact of vaccination, representing mechanisms after vaccine delivery (n = 13 impact mechanisms), their associated health effects (n = 10 health effects for beneficiary and others), and economic benefits (n = 13 immediate and secondary economic benefits and costs). Mechanisms that, when interrupted or delayed, can result in populations becoming hard-to-reach include getting vaccines and key stakeholders (e.g., beneficiaries/caregivers, vaccinators) to a vaccination site, as well as vaccine administration at the site.ConclusionDecision-makers can use this systems map to understand where steps in the vaccination process may be interrupted or weak and identify where gaps exist in the understanding of the economics of vaccination. With improved understanding of system-wide effects, this map can help decision-makers inform targeted interventions and policies to increase vaccination coverage in hard-to-reach populations.     

AIDSVAX protein boost improves breadth and magnitude of vaccine-induced HIV-1 envelope-specific responses after a 7-year rest period

BackgroundEliciting durable humoral immunity with sufficient breadth and magnitude is important for HIV-1 vaccine design. The HVTN 114 vaccine trial evaluated different boost regimens administered after a 7-year rest period in participants previously enrolled in HVTN 205, who received either three MVA/HIV62B (MMM) or two DNA and two MVA/HIV62B (DDMM) injections; both vaccines expressed multiple HIV-1 antigens in non-infectious virus-like-particles. The primary objective of HVTN 114 was to assess the impact of a heterologous gp120 protein AIDSVAX B/E boost on the magnitude, breadth and durability of vaccine-induced immune responses.MethodsWe enrolled 27 participants from HVTN 205 into five groups. Eight participants who previously received MMM were randomized and boosted with either MVA/HIV62B alone (T1; n = 4) or MVA/HIV62B and AIDSVAX B/E (T2; n = 4). Nineteen participants who received DDMM were randomized and boosted with MVA/HIV62B alone (T3; n = 6), MVA/HIV62B and AIDSVAX B/E (T4; n = 6), or AIDSVAX B/E alone (T5; n = 7). Boosts were at months 0 and 4. Participants were followed for safety and immunogenicity for 10 months and were pooled for analysis based on the regimen: MVA-only (T1 + T3), MVA + AIDSVAX (T2 + T4), and AIDSVAX-only (T5).ResultsAll regimens were safe and well-tolerated. Prior to the boost vaccination, binding antibody and CD4+T-cell responses were observed 7 years after HVTN 205 vaccinations. Late boosting with AIDSVAX, with or without MVA, resulted in high binding antibody responses to gp120 and V1V2 epitopes, with increased magnitude and breadth compared to those observed in HVTN 205. Late boosting with MVA, with or without AIDSVAX, resulted in increased gp140 and gp41 antibody responses and higher CD4+T-cell responses to Env and Gag.ConclusionsLate boosting with AIDSVAX, alone or in combination with MVA, can broaden binding antibody responses and increase T-cell responses even years following the original MVA/HIV62B with or without DNA-priming vaccine.     

Let's talk about COVID-19 vaccination: Relevance of conversations about COVID-19 vaccination and information sources on vaccination intention in Switzerland

BackgroundCOVID-19 vaccine hesitancy is known to be more pronounced among young people. However, there are a lack of studies examining determinants of COVID-19 vaccination intention in the general population in this young age-group in Switzerland, and in particular, studies investigating the influence of information sources and social networks on vaccination intention are missing.MethodsThe cross-sectional study “COVIDisc – Discussion with young people about the corona pandemic” provided the opportunity to investigate COVID-19 vaccination intention in 893 individuals aged 15–34 years from the cantons of Zurich, Thurgau, and Ticino in Switzerland. An online survey was administered between 10 November 2020 and 5 January 2021. Associations of public information sources and conversations about COVID-19 with COVID-19 vaccination intention were analyzed with multivariable logistic regression and mediation analysis using generalized structural equation modeling.Results51.5% of the participants intended or probably intended to get vaccinated once the vaccine would be available. Using print or online news (AOR 1.50, 95% CI 1.09–2.07) as an information source and having conversations about the COVID-19 vaccine (AOR 2.09, 95% CI 1.52–2.87) increased participants' COVID-19 vaccination intention. The effects of female gender (b = −0.267, p = 0.039) and risk perception (b = 0.163, p = 0.028) were partially mediated by having conversations about the COVID-19 vaccine. The effects of age (b = −0.036, p = 0.016), secondary educational level (b = 0.541, p = 0.010) and tertiary educational level (b = 0.726, p = 0.006) were fully mediated via having conversations about the COVID-19 vaccine.ConclusionsConversations and campaigns should start even before vaccines become available. Our data support interventions for young women and less educated people using social norms and supporting information seeking with news. Trust and risk perceptions are essential foundations for vaccine intentions.