High-dose Vaccine Research Articles

A chimpanzee adenoviral vector-based rabies vaccine protects beagle dogs from lethal rabies virus challenge

Rabies continues to poses serious threats to the public health in many countries. The development of novel inexpensive, safe and effective vaccines has become a high priority for rabies control worldwide. We previously generated a novel recombinant rabies vaccine by cloning rabies virus glycoprotein into a chimpanzee adenoviral vector, termed ChAd68-Gp. The present study evaluated the immune responses and protection afforded by this vaccine in beagle dogs. The results demonstrated that intramuscular immunization with both low-dose and high-dose of ChAd68-Gp induced strong immune responses and provided complete protection in beagles even at low-dose. However, when administered orally, high-dose vaccination was protective while low-dose vaccination was ineffective. Further investigation indicated that the low-pH value of gastric juice in the stomach of beagles might decompose the adenovirus. Therefore, suitable formulation for adenovirus-based oral vaccine should be considered and developed. The chimpanzee adenovirus-vectored rabies vaccine ChAd68-Gp warrants extensive test for clinical application.

First-in-Human Randomized Study to Assess the Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus (RSV) Vaccine Based on Chimpanzee-Adenovirus-155 Viral Vector-Expressing RSV Fusion, Nucleocapsid, and Antitermination Viral Proteins in Healthy Adults.

BackgroundRespiratory syncytial virus (RSV) disease is a major cause of infant morbidity and mortality. This Phase I, randomized, observer-blind, placebo- and active-controlled study evaluated an investigational vaccine against RSV (ChAd155-RSV) using the viral vector chimpanzee-adenovirus-155, encoding RSV fusion (F), nucleocapsid, and transcription antitermination proteins.MethodsHealthy 18–45-year-old adults received ChAd155-RSV, a placebo, or an active control (Bexsero) at Days (D) 0 and 30. An escalation from a low dose (5 × 109 viral particles) to a high dose (5 × 1010 viral particles) occurred after the first 16 participants. Endpoints were solicited/unsolicited and serious adverse events (SAEs), biochemical/hematological parameters, cell-mediated immunogenicity by enzyme-linked immunospot, functional neutralizing antibodies, anti RSV-F immunoglobin (Ig) G, and ChAd155 neutralizing antibodies.ResultsThere were 7 participants who received the ChAd155-RSV low dose, 31 who received the ChAd155-RSV high dose, 19 who received the placebo, and 15 who received the active control. No dose-related toxicity or attributable SAEs at the 1-year follow-up were observed. The RSV-A neutralizing antibodies geometric mean titer ratios (post/pre-immunization) following a high dose were 2.6 (D30) and 2.3 (D60). The ratio of the fold-rise (D0 to D30) in anti-F IgG over the fold-rise in RSV-A–neutralizing antibodies was 1.01. At D7 after the high dose of the study vaccine, the median frequencies of circulating B-cells secreting anti-F antibodies were 133.3/106 (IgG) and 16.7/106 (IgA) in peripheral blood mononuclear cells (PBMCs). The median frequency of RSV-F–specific interferon γ–secreting T-cells after a ChAd155-RSV high dose was 108.3/106 PBMCs at D30, with no increase after the second dose.ConclusionsIn adults previously naturally exposed to RSV, ChAd155-RSV generated increases in specific humoral and cellular immune responses without raising significant safety concerns.Clinical Trials RegistrationNCT02491463.

Effect of Age on Relative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccines Among US Medicare Beneficiaries Aged ≥65 Years.

Studies have found that the high-dose influenza vaccine has a higher relative vaccine effectiveness (RVE) versus standard-dose vaccines in some seasons. We evaluated the effect of age on the RVE of high-dose versus standard-dose influenza vaccines among Medicare beneficiaries. A 6-season retrospective cohort study from 2012 to 2018 among Medicare beneficiaries aged ≥65 years was performed. Poisson regression was used to evaluate the effect of age on the RVE of high-dose versus standard-dose influenza vaccines in preventing influenza-related hospitalizations. The study included >19 million vaccinated beneficiaries in a community pharmacy setting. The Poisson models indicated a slightly increasing trend in RVE with age in all seasons. The high-dose vaccine was more effective than standard-dose vaccines in preventing influenza-related hospital encounters (ie, influenza-related inpatient stays and emergency department visits) in the 2012-2013 (RVE, 23.1%; 95% confidence interval [CI], 17.6%-28.3%), 2013-2014 (RVE, 15.3%; 95% CI, 7.8%-22.3%), 2014-2015 (RVE, 8.9%; 95% CI, 5.6%-12.1%), and 2016-2017 (RVE, 12.6%; 95% CI, 6.3%-18.4%) seasons and was at least as effective in all other seasons. We also found that the high-dose vaccine was consistently more effective than standard-dose vaccines across all seasons for people aged ≥85 years. Similar trends were observed for influenza-related inpatient stays. The RVE of high-dose versus standard-dose influenza vaccines increases with age.

Enhanced immunogenicity and protective efficacy of a tetravalent dengue DNA vaccine using electroporation and intradermal delivery

Phase 1 clinical trials with a DNA vaccine for dengue demonstrated that the vaccine is safe and well tolerated, however it produced less than optimal humoral immune responses. To determine if the immunogenicity of the tetravalent dengue DNA vaccine could be enhanced, we explored alternate, yet to be tested, methods of vaccine administration in non-human primates. Animals were vaccinated on days 0, 28 and 91 with either a low (1 mg) or high (5 mg) dose of vaccine by the intradermal or intramuscular route, using either needle-free injection or electroporation devices. Neutralizing antibody, IFN-γ T cell and memory B cell responses were compared to a high dose group vaccinated with a needle-free intramuscular injection delivery device similar to what had been used in previous preclinical and clinical studies. All previously untested vaccination methodologies elicited improved immune responses compared to the high dose needle-free intramuscular injection delivery group. The highest neutralizing antibody responses were observed in the group that was vaccinated with the high dose formulation via intradermal electroporation. The highest IFN-γ T cell responses were also observed in the high dose intradermal electroporation group and the CD8+ T cells were the dominant contributors for the IFNγ response. Memory B cells were detected for all four serotypes. More than a year after vaccination, groups were challenged with dengue-1 virus. Both the low and high dose intradermal electroporation groups had significantly fewer days of dengue-1 virus RNAemia compared to the control group. The results from this study demonstrate that using either an electroporation device and/or the intradermal route of delivery increases the immune response generated by this vaccine in non-human primates and should be explored in humans.

Surveillance for Guillain-Barré syndrome after influenza vaccination among U.S. Medicare beneficiaries during the 2017–2018 season

BackgroundThe U.S. Food and Drug Administration and the Centers for Medicare & Medicaid Services have been actively monitoring the risk of Guillain-Barré syndrome (GBS) following influenza vaccination among Fee-for-Service (FFS) Medicare beneficiaries every season since 2008. We present our evaluation of the GBS risk following influenza vaccinations during the 2017–2018 season. MethodsWe implemented a multilayered approach to active safety surveillance that included near real-time surveillance early in the season, comparing GBS rates post-vaccination during the 2017–2018 season with rates from five prior seasons using the Updating Sequential Probability Ratio Test (USPRT), and end-of-season self-controlled risk interval (SCRI) analyses. ResultsWe identified approximately 16 million influenza vaccinations. The near real-time surveillance did not signal for a potential 2.5-fold increased GBS risk either in days 8–21 or 1–42 post-influenza vaccination. In the SCRI analyses, we did not detect statistically significant increased GBS risks among influenza-vaccinated Medicare beneficiaries ≥65 years for either the 8–21 or 1–42-day risk windows for all seasonal vaccines combined, high-dose vaccine, or standard-dose vaccines; we did detect an increased GBS risk in days 8–21 post-vaccination for individuals vaccinated with the adjuvanted vaccine (OR: 3.75; 95% CI: 1.01, 13.96), although this finding was not statistically significant after multiplicity adjustment (p = 0.146). ConclusionsOur multilayered surveillance approach—which allows for early detection of elevated GBS risk and provides reliable end-of-season SCRI estimates of effect size—did not identify an increased GBS risk following 2017–2018 influenza vaccinations. The slightly increased GBS risk with the adjuvanted vaccine, which was not statistically significant following multiplicity adjustment, is consistent with the package inserts of all U.S.-licensed influenza vaccines, which warn of a potential low increased GBS risk. The benefits of influenza vaccines in preventing morbidity and mortality heavily outweigh this potential risk.

Alternative-Dose versus Standard-Dose Trivalent Influenza Vaccines for Immunocompromised Patients: A Meta-Analysis of Randomised Control Trials

The study compared immunogenicity and safety between alternative higher-dose and standard-dose trivalent vaccines in immunocompromised individuals. A literature search was performed using the PubMed, Embase, and Cochrane databases from inception until March 2019 to identify studies comparing the immunogenicity of alternative higher-dose (including high-dose, double-dose, and booster-dose vaccines) and standard-dose trivalent influenza vaccines in patients who underwent transplantation or chemotherapy. Effect estimates from the individual studies were derived and calculated using the DerSimonian and Laird random-effect model. The protocol for this systematic review is registered with PROSPERO (number CRD42019129220). Eight relevant studies involving 1020 patients were included in the systematic review and meta-analysis. The meta-analysis demonstrated that the higher-dose strategy provided had significantly superior seroconversion and seroprotection for A/H1N1 strains than the standard dose. Regarding H3N2 and B strains, no differences in immunogenicity responses were noted. No differences in safety were observed between the vaccination strategies. Alternative higher-dose vaccination strategies appear to associate with superior immunogenicity responses for A/H1N1 strains, and the strategies were generally well tolerated in immunocompromised populations. Future studies should clarify the optimal timing, frequency and dose of vaccination and assess whether these strategies improve vaccine immunogenicity and clinical outcomes.

High dose hepatitis B vaccine is not effective in patients using immunomodulatory drugs: a pilot study

ABSTRACTIn patients undergoing immunotherapy, the quality of the immune response is reduced, which may negatively affect the efficacy of vaccination. This study was conducted in order to evaluate the efficacy of the hepatitis B virus (HBV) vaccine in patients using immunomodulators. Seronegative patients for HBV who were using biological agents, were included in the study. The vaccination was administered on the standard schedule in 3 doses of 20 or 40 µg/ml. Eighty-two patients (52%) were males and the mean age of all patients was 44,8 ± 10,3 years. Among these 109 patients, 83 had psoriasis, 12 had Crohn’s disease, six had rheumatoid arthritis, three had ulcerative colitis, three had hydradenitis supurativa, one had Behcet’s disease and one had ankylosing spondylitis. The biological agents that were being used by these patients were adalimumab (62), ustekinumab (25), infliximab (12), etanercept (9) and golimumab (1). Seventy-three of the patients were vaccinated with a dose of 20 µg/ml and 36 with 40 µg/ml. The anti-HBs titers of fifty-eight (53.2%) patients were above 10 mIU/ml. The antibody response rate was lowest in infliximab-users (16.7%) (p = 0.007), which was followed by adalimumab (48.4%), and higher protection rates were achieved in patients using ustekinumab and etanercept (72% and 88.9%, respectively; p < 0.05). The HBV vaccine response rate in patients using immunomodulators was significantly lower than that in immunocompetent patients. Furthermore, high dose vaccination did not increase the response rate. Clinicians should take into account administering HBV vaccination before treatment with biological agent in patients who have negative HBV serology.

Assessing Residual Bias in Estimating Influenza Vaccine Effectiveness

Estimating influenza vaccine effectiveness using an unvaccinated comparison group may result in biased effect estimates. To explore the reduction of confounding bias in an active comparison of high-dose versus standard-dose influenza vaccines, as compared with vaccinated versus unvaccinated comparisons. Using Medicare data from the United States end-stage renal disease program (2009-2013), we compared the risk of all-cause mortality among recipients of high-dose vaccine (HDV) versus standard-dose vaccine (SDV), HDV versus no vaccine, and SDV versus no vaccine. To quantify confounding bias, analyses were restricted to the preinfluenza season, when the protective effect of vaccination should not yet be observed. We estimated the standardized mortality ratio-weighted cumulative incidence functions using Kaplan-Meier methods and calculated risk ratios (RRs) and risk differences between groups. Among 350,921 eligible patients contributing 825,642 unique patient preinfluenza seasons, 0.8% received HDV, 70.5% received SDV, and 28.7% remained unvaccinated. Comparisons with unvaccinated patients yielded spurious decreases in mortality risk during the preinfluenza period, for HDV versus none [RR, 0.60; 95% confidence interval (CI), 0.51-0.70)] and SDV versus none (RR, 0.72; 95% CI, 0.70-0.75). The effect estimate was attenuated in the HDV versus SDV comparison (RR, 0.89; 95% CI, 0.77-1.03). Estimates on the absolute scale followed a similar pattern. The HDV versus SDV comparison yielded less-biased estimates of the all-cause mortality before influenza season compared to those with nonuser comparison groups. Vaccine effectiveness and safety researchers should consider the active comparator design to reduce bias due to differences in underlying health status between vaccinated and unvaccinated individuals.

Revisiting the Safety of Vaccination against the Flu in Elderly Patients

Abstract. Elderly patients are at higher risk of developing infectious diseases that might have more severe progression than those of younger age groups, accompanied by an increased risk of death. These medical conditions in elderly may also present difficulties for diagnosis due to a «blurred» clinical picture. By WHO recommendations the vaccination against influenza is one of the most effective ways to prevent this type of infection in elderly patients. However the use of vaccines may be associated with a risk of adverse drug reactions. In most cases, they have subclinical manifestations and/or non-severe clinical manifestations (adverse reactions), but in a relatively small percentage of cases, the use of vaccines may be associated with a risk of developing serious post-vaccination complications (anaphylaxis, Guillain-Barre syndrome etc.). This article represents data on the safety of influenza vaccines in patients over 60 years old, with due regard to immunosenescence. According to the authors opinion, this will improve the safety of vaccination against influenza patients 60 years and older. At the end of the article, the authors conclude that despite the potential risks, the by the benefits of the use of influenza vaccines continue to overweight potential risks and vaccination of elderly people is effective and safe way to prevent influenza. To improve the effectiveness of vaccination of patients 60 years and older the use of high dose vaccines and adjuvants can be recommended.

2504. Influenza Surveillance and Outbreaks in the US Department of Veterans Affairs (VA): 2017–2018 Season

BackgroundVA conducts yearly surveillance for seasonal influenza. VA’s large elderly population is at higher risk for influenza complications, including hospitalization and death. Herein we summarize 2017–2018 national influenza activity, outbreak and vaccination data for VA.MethodsHospitalizations, outpatient visits, influenza testing, and antivirals were obtained from VA data sources (October 1, 2017–March 31, 2018) and compared with prior seasons. Vaccines were captured from August 1, 2017 and vaccination percentage calculated based on VA users for each fiscal year. Outbreak data were collected from VA Issue Briefs and email survey of facility Infection Preventionists.ResultsSurveillance metrics for 6 seasons are presented (table). In 2017–2018, high-dose (HD) vaccine increased to 20% of total vaccine given. Outpatient visits, hospitalizations, confirmed cases and antiviral prescriptions were more than double that of previous seasons. 46 distinct outbreaks at 35 different VA hospitals were also reported this season. Among 31,611 laboratory-confirmed influenza (LCI) cases, Veterans with vaccination >14 days prior to LCI were significantly more likely to have an influenza-related hospitalization than those with no documented vaccination (782, 29% vs. 5,888, 21%, P < 0.01) and were less likely to have received HD vaccine compared with the overall VA patient population (375; 14% vs. 365,357; 20%, P < 0.01) (figure).ConclusionThe 2017–18 season was the most severe since VA surveillance was initiated in 2009. HD vaccine use increased over the seasons evaluated, but overall vaccination levels were stable. Nearly 90% of those with LCI had no VA-documented vaccination this season, although some may have received vaccine outside VA. Overall hospitalization rate for Veterans with LCI was high (22%). Vaccination did not reduce the likelihood of being hospitalized with influenza; however, HD vaccine may have afforded some additional protection compared with standard dose. Disclosures All authors: No reported disclosures.

150. Relative Effectiveness of High-Dose and Standard-Dose Influenza Vaccine Against Influenza-Related Hospitalization Among Older Adults—United States, 2015–2017

BackgroundSeasonal influenza causes substantial morbidity and mortality, and older adults are disproportionately affected. Newer vaccines have been developed for use in people 65 years and older, including a trivalent inactivated vaccine with a 4-fold higher dose of antigen (IIV-HD). In recent years, the use of IIV-HD has increased sufficiently to evaluate its effectiveness compared with standard-dose inactivated influenza vaccines (IIV-SD).MethodsHospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in 4 states participating in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Predominant influenza A virus subtypes were H1N1 and H3N2, respectively, during these seasons. All enrolled patients were tested for influenza virus with polymerase chain reaction. Receipt and type of influenza vaccine was determined from electronic records and chart review. Odds of laboratory-confirmed influenza were compared among vaccinated and unvaccinated patients. Relative odds of laboratory-confirmed influenza were determined for patients who received IIV-HD or IIV-SD, and adjusted for potential confounding variables via logistic regression.ResultsAmong 1,744 enrolled patients aged ≥ 65 years, 1,105 (63%) were vaccinated; among those vaccinated, 621 (56%) received IIV-HD and 484 (44%) received IIV-SD. Overall, 315 (18%) tested positive for influenza, including 97 (6%) who received IIV-HD, 86 (5%) who received IIV-SD, and 132 (8%) who were unvaccinated. Controlling for age, race, sex, enrollment site, date of illness, index of comorbidity, and influenza season, the adjusted odds of influenza among patients vaccinated with IIV-HD vs. IIV-SD were 0.72 (P = 0.06, 95% CI: 0.52 to 1.01).ConclusionComparison of high-dose vs. standard-dose vaccine effectiveness during 2 recent influenza seasons (1 H1N1 and 1 H3N2-predominant) suggested relative benefit (nonsignificant) of high-dose influenza vaccine in protecting against influenza-associated hospitalization among persons aged 65 years and older; additional years of data are needed to confirm this finding.Disclosures H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

991. Randomized Trial of High Dose, Adjuvanted, and Standard Inactivated Influenza Vaccine Immune Response Against Egg- and Cell-Propagated Vaccine Strains in Older Adults, 2016–2017 Season

BackgroundHigh dose (HD-IIV), standard dose (SD-IIV), and MF-59 adjuvanted (aIIV) influenza vaccines are licensed for adults ≥65 years old, but there is no preferential recommendation for a specific product. These vaccines are manufactured using egg-adapted high growth reassortant viruses. Recent data suggest that antibodies generated by egg-adapted A(H3N2) viruses may contribute to reduced vaccine effectiveness. We report results from the first year of a 2-year randomized trial of vaccine immunogenicity, including response to A(H3N2) vaccine strains propagated in egg (H3N2-egg) and cell culture (H3N2-cell).MethodsAdults 65–74 years old were randomized to receive 2016–2017 trivalent inactivated influenza vaccines: SD-IIV (n = 60), HD-IIV (n = 59), and aIIV (n = 60). Pre- and post-vaccination sera were analyzed by microneutralization assays (MN) to egg- and cell-propagated A(H3N2) vaccine virus, A/Hong Kong/4801/2014 and tested by hemagglutination inhibition (HI) assays to A/California/7/2009 A(H1N1)pdm09-like and B/Brisbane/60/2008-like viruses. Endpoints were postvaccination geometric mean titer (GMT), mean fold rise (MFR), and seroconversion. Respiratory swabs from adults with acute respiratory illness during the season were tested by RT-PCR to identify vaccine failures.ResultsPrevaccination MN and HI titers were similar across study arms. There were no differences across study arms in postvaccination MN GMT, seroconversion, and MFR against H3N2-egg and H3N2-cell (figure). However, response was lower against H3N2-cell than H3N2-egg. HI MFR for H1N1pdm09 and B/Brisbane were significantly higher in HD-IIV than SD-IIV and aIIV recipients (figure). Eight participants had PCR-confirmed A(H3N2) infection: 1/60 (2%) SD-IIV, 4/57 (7%) HD-IIV, and 3/60 (5%) aIIV recipients. Postvaccination H3N2-cell MN GMT was 15 and 63, respectively for A(H3N2) cases and noncases. Among the eight A(H3N2) cases, postvaccination MN titers were ≥1:40 against H3N2-egg for 6 cases vs. 0 cases against H3N2-cell.ConclusionPostvaccination MN titers against H3N2 egg- and cell-propagated vaccine viruses were similar across study arms, although antibody response was lower to H3N2-cell. HD-IIV generated greater antibody response against A(H1N1)pdm09 and B compared with SD-IIV or aIIV.Disclosures All authors: No reported disclosures.

High-Dose Seasonal Influenza Vaccine in Patients Undergoing Dialysis.

High-dose influenza vaccine, which contains fourfold more antigen than standard dose, is associated with fewer cases of influenza and less influenza-related morbidity in the elderly general population. Whether the high-dose influenza vaccine benefits patients on dialysis, whose immune response to vaccination is less robust than that of healthy patients, is uncertain. We compared hospitalizations and deaths during the 2015-2016 and 2016-2017 influenza seasons by vaccine type (standard trivalent, standard quadrivalent, and high-dose trivalent influenza vaccine) administered within a national dialysis organization. The association of vaccine type with outcomes was estimated using Cox proportional hazards regression with adjustment for patient factors and "center effect." Analyses were stratified by age and dialysis modality. Between September 1 and December 31, 2015, standard dose trivalent, standard dose quadrivalent, and high-dose trivalent influenza vaccines were administered to 3057 (31%), 5981 (61%), and 805 (8%) patients, respectively. The adjusted rates of first hospitalizations by vaccine type during the influenza season were 8.43, 7.88, and 7.99 per 100 patient-months, respectively, and the adjusted rates of death were 1.00, 0.97, and 1.04, respectively. These differences were not significant. In 2016, 3614 (39%) received quadrivalent vaccine, and 5700 (61%) received high-dose trivalent vaccine. The adjusted rates of first hospitalization by vaccine type were 8.71 and 8.04 per 100 patient-months, respectively, and the adjusted rates of death were 0.98 and 1.02, respectively. Receipt of high dose was associated with a significant reduction in hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.86 to 1.00; P=0.04); there was no significant association with death. There was no significant heterogeneity of either association by age group or dialysis modality. Receipt of high-dose compared with standard dose influenza vaccine in 2016-2017 was associated with lower rates of hospitalization in patients on dialysis, although that was not seen in 2015-2016.

Assessing the effectiveness of high-dose influenza vaccine in preventing hospitalization among seniors, and observations on the limitations of effectiveness study design

BackgroundThe availability of high-dose (HD) influenza vaccine for seniors should decrease influenza-related hospitalization. Studies to date show a range of mostly moderate increased HD vaccine effectiveness (VE). While a ‘healthy vaccinee’ phenomenon can inflate VE, for influenza and particularly an HD vaccine targeted at frailer adults, an ‘at-risk vaccinee’ bias may deflate VE estimates. We assessed senior HD vaccine effectiveness against influenza-related hospitalization by linking immunization registry records to hospitalizations. We also examined whether adding strata typically ignored in case-control matching schemas, such as residence areas, exact age, and provider biases, would increase VE. MethodsFor the 2016–17 influenza season in the Portland metropolitan area, the differential VE for the HD vaccine in preventing PCR-confirmed influenza hospitalization was assessed by a nested series of models across matching strata. For an exact match for high-dose and standard-dose seniors, matching elements included exact age, gender, residence type, race-ethnicity, provider bias, and residence area (zipcode). ResultsAs a first step, a simple aggregate comparison of influenza-related hospitalization risk showed no added HD effectiveness. For the nested models, adding strata increased VE. In the final model, among 23,712 matched pairs of HD to SD vaccinated seniors, the HD vaccine was 30.7% (95%CI: 8–48%) more effective in preventing influenza-related hospitalization. ConclusionFor this study, the high-dose influenza vaccine provided superior protection for seniors against influenza hospitalization. Including matching elements as exact year of age and residence zipcode all added to the calculation of VE. As a warning, non-matched or overly simple matched VE study designs may substantially under-estimate VE.

Flu, Pneumococcal Vaccination Rates on the Rise

Flu, Pneumococcal Vaccination Rates on the Rise

Communicator or Shill?

Communicator or Shill?

Canadian older adults’ perceptions of effectiveness and value of regular and high-dose influenza vaccines

ABSTRACTInfluenza vaccination is an important public health intervention for older adults, yet vaccination rates remain suboptimal. We conducted an online survey of Canadians ≥ 65 years to explore satisfaction with publicly-funded standard-dose influenza vaccines, and perceptions of the need for a more effective product. They were provided with information about currently approved influenza vaccines, and were asked about their preferences should all formulations be available for free, and should the recently approved high-dose (HD) vaccine for seniors be available at a cost. From March to April 2017, 5014 seniors completed the survey; mean age was 71.3 ± 5.17 years, 50% were female, and 42.6% had one or more chronic conditions. 3403 (67.9%) had been vaccinated against influenza in the 2016/17 season. Of all respondents, 3460 (69%) were satisfied with the standard-dose influenza vaccines, yet 3067 (61.1%) thought that a more effective vaccine was/may be needed. If HD was only available at a cost, 1426 (28.4%) respondents would consider it, of whom 62.9% would pay $20 or less. If all vaccines were free next season, 1914 (38.2%) would opt for HD (including 12.2% of those who previously rejected influenza vaccines), 856 (17.1%) would choose adjuvanted vaccine, and 558 (11.1%) standard-dose vaccine. 843 (16.8%) of respondents were against vaccines, 451 (9.0%) had no preference and 392 (7.8%) were uncertain. Making this product available through publicly funded programs may be a strategy to increase immunization rates in this population.

High-dose influenza vaccine use among patients receiving hemodialysis in the United States, 2010–2013

BackgroundStandard influenza vaccines may be of limited benefit to patients with end-stage renal disease (ESRD). These patients may benefit from high-dose influenza vaccine, currently indicated for patients aged ≥65 years. Studies in other populations have demonstrated that high-dose vaccine elicits a stronger immunological response. We compared vaccine uptake in the United States and predictors of receipt for high-dose and standard influenza vaccines. MethodsUsing data from the United States Renal Data System (2010–2013), we conducted a cohort study of 421,482 adult patients on hemodialysis. We examined temporal trends in uptake of high-dose or standard trivalent influenza vaccine each influenza season, and used multivariate logistic regression to assess the association between individual-level variables (e.g., demographics, comorbidities) and facility-level variables (e.g., facility size and type) with vaccine receipt. ResultsThe proportion of patients with ESRD who were vaccinated with any influenza vaccine increased from 68.3% in 2010 to 72.4% in 2013. High-dose vaccines were administered to 0.9% of patients during the study period, and 16.7% of high-dose vaccines were administered to patients <65 years of age. Among patients aged ≥65 years, older patients (>79 vs. 65–69 years: OR, 1.29; 95% CI, 1.19–1.41) and patients at hospital-based versus free-standing dialysis facilities (OR, 2.31; 95% CI, 2.13–2.45) were more likely to receive high-dose vaccine, while blacks (vs. whites [OR, 0.66; 95% CI, 0.61–0.71]) and patients with longer duration of ESRD (>9 vs. 0 years: OR, 0.66; 95% CI, 0.55–0.78) were less likely to receive the high-dose vaccine. ConclusionsWhile the overall influenza vaccination rate has increased, use of high-dose vaccine among patients with ESRD was very low. Being an older patient, living in the Midwest, and receiving care at hospital-based facilities were the strongest predictors of receiving high-dose vaccine.

Potential Cost-Effectiveness of a Universal Influenza Vaccine in Older Adults.

Background and Objectives“Universal” vaccines that could have multistrain and multiyear effectiveness are being developed. Their potential cost-effectiveness in geriatric populations is unknown.Research Design and MethodsA Markov model estimated effects of a theoretical universal influenza vaccine compared with available seasonal vaccines in hypothetical cohorts of U.S. 65+-year olds followed over a 5-year time horizon to capture potential multiyear protection. Outcomes included costs per quality-adjusted life-year gained and influenza cases avoided.ResultsUsing hypothetical universal vaccine parameter values (cost $100, vaccine effectiveness 39%, uptake 64%, effectiveness duration 5 years), universal vaccine was less costly than seasonal influenza vaccination strategies. High-dose trivalent influenza vaccine, compared with universal vaccine, gained 0.0028 quality-adjusted life-years and cost $82 more, or $28,700 per quality-adjusted life-year gained. Other seasonal vaccines were not favorable economically. Five-year influenza risk with universal vaccination was 32.3% under base case assumptions, compared with <30% with adjuvanted or high-dose vaccine use. In sensitivity analyses, universal vaccine was favored when uptake or vaccine effectiveness was greater than standard-dose influenza vaccine. If absolute universal vaccine effectiveness was 10% less than standard-dose vaccine, universal vaccine could be cost-saving but not more effective than other strategies. Universal vaccine was not favored if its effectiveness duration was <3 years.Discussion and ImplicationsUniversal vaccine use in older persons could be either cost effective or cost saving when universal vaccine parameters are within plausible ranges. However, if its effectiveness is substantially less than current vaccines, its use would probably not be favored in geriatric populations.

Immunogenicity and safety of double versus standard dose of the seasonal influenza vaccine in solid-organ transplant recipients: A randomized controlled trial

BackgroundThe use of vaccines with higher doses of antigen is an attractive strategy to improve the immunogenicity of influenza vaccination in transplant recipients. However, the effect of vaccination with a double-dose (DD) containing 30 µg of antigen in this population remains unknown. MethodsWe performed a randomized controlled trial to compare the immunogenicity and safety of DD (30 µg) vs. standard dose (SD, 15 µg) of a trivalent inactivated influenza vaccine in kidney and liver transplant recipients. Immunogenicity was assessed by hemagglutination-inhibition assay. Vaccine response was defined as seroconversion to at least one viral strain 2 weeks after vaccination and seroprotection as a titer ≥40. ResultsSixty-three kidney and 16 liver transplant recipients were enrolled. Forty patients received the DD and 39 the SD vaccine. Overall, 40% of patients in the DD compared to 26% in the SD group (P = 0.174) responded to vaccine. In the DD arm, more patients were seroprotected to all viral strains after vaccination (88% vs 69%, P = 0.048). Post vaccination geometric mean titers of antibodies were 131.9 vs. 89.7 (P = 0.187) for H1N1, 185.4 vs. 138.7 (P = 0.182) for H3N2, and 96.6 vs. 68.8 (P = 0.081) for influenza B with the DD vs. SD. In both groups, most of the adverse events were mild and no vaccine-related severe adverse events were observed. ConclusionDouble-dose influenza vaccine is safe and may increase antibody response in transplant recipients. In this population, DD vaccination could be an alternative when high-dose vaccine is not available. NCT02746783.