Quadrivalent Influenza Vaccine Research Articles

Characterization of "Off-Target" Immune Modulation Induced by Live Attenuated Yellow Fever Vaccine.

Live attenuated vaccines alter immune functions and are associated with beneficial outcomes. We previously demonstrated that live attenuated yellow fever virus (YFV) vaccine (LA-YF-Vax) dampens T-cell receptor (TCR) signaling in vitro via an RNA-based mechanism. We examined study participants before and after LA-YF-Vax to assess TCR-mediated functions in vivo. Serum samples and peripheral blood mononuclear cells (PBMCs) were obtained before and after LA-YF-Vax (with or without additional vaccines) or quadrivalent influenza vaccine. TCR-mediated activation was determined by interleukin 2 release or phosphorylation of the lymphocyte-specific Src kinase. TCR-regulating phosphatase (protein tyrosine phosphatase receptor type E [PTPRE]) expression was also measured. Compared with prevaccination findings, LA-YF-Vax recipient PBMCs demonstrated transient reduction in interleukin 2 release after TCR stimulation and PTPRE levels, unlike in control participants who received quadrivalent influenza vaccine. YFV was detected in 8 of 14 participants after LA-YF-Vax. After incubation of healthy donor PBMCs in serum-derived extracellular vesicles prepared from LA-YF-Vax recipients, TCR signaling and PTPRE levels were reduced after vaccination, even in participants without detectable YFV RNA. LA-YF-Vax reduces TCR functions and PTPRE levels after vaccination. Extracellular vesicles from serum recapitulated this effect in healthy cells. This likely contributes to the reduced immunogenicity for heterologous vaccines after LA-YF-Vax administration. Identification of specific immune mechanisms related to vaccines should contribute to understanding of the "off-target," beneficial effects of live vaccines.

Cost-Effectiveness of Vaccination of Older Adults with an MF59®-Adjuvanted Quadrivalent Influenza Vaccine Compared to Standard-Dose and High-Dose Vaccines in Denmark, Norway, and Sweden.

Individuals aged 65 years and above are at increased risk of complications and death from influenza compared with any other age group. Enhanced vaccines, as the MF59®-adjuvanted quadrivalent influenza vaccine (aQIV) and the high-dose quadrivalent influenza vaccine (HD-QIV), provide increased protection for older adults in comparison to the traditional standard-dose quadrivalent influenza vaccines (SD-QIV). This study aimed to assess the cost-effectiveness of aQIV compared to SD-QIV and HD-QIV in Denmark, Norway, and Sweden for adults aged ≥65 years. A static decision tree model was used to evaluate costs and outcomes of different vaccination strategies from healthcare payer and societal perspectives. This model projects that compared to SD-QIV, vaccination with aQIV could prevent a combined total of 18,772 symptomatic influenza infections, 925 hospitalizations, and 161 deaths in one influenza season across the three countries. From a healthcare payer perspective, the incremental costs per quality adjusted life year (QALY) gained with aQIV versus SD-QIV were EUR 10,170/QALY in Denmark, EUR 12,515/QALY in Norway, and EUR 9894/QALY in Sweden. The aQIV was cost saving compared with HD-QIV. This study found that introducing aQIV to the entire population aged ≥65 years may contribute to reducing the disease and economic burden associated with influenza in these countries.

Superior immunogenicity of high-dose quadrivalent inactivated influenza vaccine versus Standard-Dose vaccine in Japanese Adults ≥ 60 years of age: Results from a phase III, randomized clinical trial

BackgroundA high-dose, split-virion inactivated quadrivalent influenza vaccine (IIV4-HD; Sanofi) is being used for the prevention of influenza in multiple countries. This study examined the immunogenicity and safety of the IIV4-HD vaccine administered intramuscularly (IM) compared with a locally licensed standard-dose influenza vaccine (IIV4-SD) administered subcutaneously (SC) in Japan. MethodsThis was a phase III, randomized, modified double-blind, active-controlled, multi-center study in older adults ≥ 60 years of age conducted during the Northern Hemisphere (NH) influenza season of 2020–21 in Japan. Participants were randomized in a 1:1 ratio to receive a single IM injection of IIV4-HD or SC injection of IIV4-SD. Hemagglutination inhibition antibody and seroconversion rates were measured at baseline and day 28. Solicited reactions were collected for up to 7 days after vaccination, unsolicited adverse events up to 28 days after vaccination, and serious adverse events throughout the study. ResultsThe study included 2100 adults ≥ 60 years of age. IIV4-HD given IM induced superior immune responses versus IIV4-SD given SC as assessed by geometric mean titers for all four influenza strains. Superior seroconversion rates were also observed for IIV4-HD compared to IIV4-SD for all influenza strains. The safety profiles of IIV4-HD and IIV4-SD were similar. IIV4-HD was well tolerated in participants, with no safety concerns identified. ConclusionsIIV4-HD provided superior immunogenicity versus IIV4-SD and was well tolerated in participants ≥ 60 years of age in Japan. With superior immunogenicity based on the multiple randomized controlled trials and real-world evidence of trivalent high-dose formulation, IIV4-HD is expected to be the first differentiated influenza vaccine in Japan that offer a greater protection against influenza and its complications in adults 60 years of age and older. Study registrationNCT04498832 (clinicaltrials.gov); U1111-1225–1085 (who.int).

AF03 adjuvant improves anti-hemagglutinin and anti-neuraminidase immune responses induced by licensed seasonal quadrivalent influenza vaccines in mice.

Seasonal influenza remains a serious public health concern as the viral infection spreads easily from person to person and due to antigenic drift of neutralizing epitopes. Vaccination is the best method for disease prevention, however current seasonal influenza vaccines stimulate antibodies which are often effective against only antigenically similar strains. To boost the immune responses and increase vaccine effectiveness, adjuvants have been used for the past 20years. The current study explores the use of oil-in-water adjuvant, AF03 to improve an immunogenicity of 2 licensed vaccines. A standard-dose inactivated quadrivalent influenza vaccine (IIV4-SD), containing both hemagglutinin (HA) and neuraminidase (NA) antigens, and recombinant quadrivalent influenza vaccine (RIV4), containing only HA-antigen were adjuvanted with AF03 in naïve BALB/c mouse model. Functional HA-specific antibody titers against all four homologous vaccine strains were enhanced by AF03, indicating potential increase in protective immunity. An increase in HA-specific total immunoglobulin G (IgG) binding titers were detected against homologous HAs, heterologous panel of 30 H3 HAs and seven Influenza B HAs. The neuraminidase inhibition (NAI) activity was significantly higher in IIV4-SD-AF03 group. Use of AF03 adjuvant improved the immune response to two influenza vaccines in a mouse model via an increase in functional and total antibodies against NA and a broad panel of HA-antigens.

Enhanced safety surveillance of GSK's quadrivalent seasonal influenza vaccine in Germany and Spain (2021/2022 season) using an electronic patient-reported outcome system for vaccine safety remote monitoring.

Seasonal influenza epidemics are managed through vaccination each winter in the European Union, to prevent infections, complications, and deaths. As circulating virus strains vary unpredictably, vaccines are reformulated annually, and their safety monitored rapidly and continuously at the start of each season, following European Medicines Agency guidelines.Seasonal influenza epidemics are managed through vaccination each winter in the European Union, to prevent infections, complications, and deaths. As circulating virus strains vary unpredictably, vaccines are reformulated annually, and their safety monitored rapidly and continuously at the start of each season, following European Medicines Agency guidelines. This enhanced safety surveillance study assessed pre-specified and other adverse events (AEs) occurring within 7 days of GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4) in children and adults in Spain and Germany. As the study was conducted during the COVID-19 pandemic (2021/2022 season), data were collected electronically, using a web portal or call center. Safety was assessed in 737 participants (median age 49 and 9 years in Germany and Spain, respectively, 19.3% with a chronic medical condition). After Dose 1 and Dose 2, respectively, 332 (45.1%) and 5 (26.3%) participants reported at least one AE, primarily pre-specified AEs. The most common AEs after Dose 1 (adults and children) were injection site pain, swelling or erythema, headache, and fatigue. After Dose 2 (in children), the most common AEs were injection site pain, rhinorrhea, fatigue, and decreased appetite. No new or unexpected safety issues were identified. This study supports and confirms the safety profile of GSK's IIV4 in all age groups with a vaccine indication. The new electronic safety reporting method (with response rates of 75.4% following Dose 1 and 100% following Dose 2) provides an alternative for future studies to reduce the burden on sites or in case site visits are not feasible.

ADCC: An underappreciated correlate of cross-protection against influenza?

In this short review, we summarized the results obtained with an assay to detect influenza virus-specific antibodies that mediate ADCC, which was developed and evaluated within the framework of the IMI-funded project "FLUCOP". HA-specific ADCC mediating antibodies were detected in serum samples from children and adults pre- and post-vaccination with monovalent, trivalent, or quadrivalent seasonal influenza vaccines, or following infection with H1N1pdm09 virus. Additionally, using chimeric influenza HA proteins, the presence of HA-stalk-specific ADCC mediating antibodies after vaccination and natural infection with H1N1pdm09 virus was demonstrated. With serum samples obtained from children that experienced a primary infection with an influenza B virus, we showed that primary infection induces HA-specific ADCC-mediating antibodies that cross-reacted with HA from influenza B viruses from the heterologous lineage. These cross-reactive antibodies were found to be directed to the HA stalk region. Antibodies directed to the influenza B virus HA head mediated low levels of ADCC. Finally, vaccination with a recombinant modified vaccinia virus Ankara expressing the HA gene of a clade 1 A(H5N1) highly pathogenic avian influenza virus led to the induction of ADCC-mediating antibodies, which cross-reacted with H5 viruses of antigenically distinct clades. Taken together, it is clear that virus-specific antibodies induced by infection or vaccination have immunological functionalities in addition to neutralization. These functionalities could contribute to protective immunity. The functional profiling of vaccine-induced antibodies may provide further insight into the effector functions of virus-specific antibodies and their contribution to virus-specific immunity.

An Economic Comparison in the Elderly of Adjuvanted Quadrivalent Influenza Vaccine with Recombinant Quadrivalent Influenza Vaccine in Spain.

Influenza infections impose a high burden of morbidity and mortality among older adults, at great cost to individuals and society. Enhanced influenza vaccines, which contain either an immune adjuvant or higher than normal doses of influenza virus antigens, are recommended for older adults. We used a health economics model to evaluate the cost effectiveness in Spain of a recently licensed recombinant quadrivalent influenza vaccine (QIVr), which contains three times the standard dose of influenza virus hemagglutinin but no neuraminidase, compared with an MF59-adjuvanted quadrivalent influenza vaccine (aQIV). Based on current tender prices in Spain and a conservative assumption that QIVr is 10.7% relatively more effective than aQIV, the incremental cost-effectiveness ratio (ICER) for QIVr was EUR 101,612.41 per quality-adjusted life year (QALY) gained. To meet the Spanish willingness-to-pay threshold of EUR 25,000 per QALY gained, QIVr would need to be 34.1% relatively more effective than aQIV. In a probabilistic sensitivity analysis conducted to confirm the robustness of the analysis, 99.7% of simulations for QIVr were higher than the willingness-to-pay curve. These findings suggest that QIVr is not currently a cost-effective influenza vaccine option relative to aQIV for older persons living in Spain.

Recommended Adult Immunization Schedule, United States, 2023.

Recommended Adult Immunization Schedule, United States, 2023.

Transverse myelitis following bivalent COVID‐19 booster vaccine and quadrivalent seasonal influenza vaccine

Transverse myelitis following bivalent <scp>COVID</scp>‐19 booster vaccine and quadrivalent seasonal influenza vaccine

The Pregnancy, Arsenic, and Immune Response (PAIR) Study in rural northern Bangladesh.

Arsenic exposure and micronutrient deficiencies may alter immune reactivity to influenza vaccination in pregnant women, transplacental transfer of maternal antibodies to the foetus, and maternal and infant acute morbidity. The Pregnancy, Arsenic, and Immune Response (PAIR) Study was designed to assess whether arsenic exposure and micronutrient deficiencies alter maternal and newborn immunity and acute morbidity following maternal seasonal influenza vaccination during pregnancy. The PAIR Study recruited pregnant women across a large rural study area in Gaibandha District, northern Bangladesh, 2018-2019. Prospective, longitudinal pregnancy and birth cohort. We conducted home visits to enrol pregnant women in the late first or early second trimester (11-17 weeks of gestational age). Women received a quadrivalent seasonal inactivated influenza vaccine at enrolment. Follow-up included up to 13 visits between enrolment and 3 months postpartum. Arsenic was measured in drinking water and maternal urine. Micronutrient deficiencies were assessed using plasma biomarkers. Vaccine-specific antibody titres were measured in maternal and infant serum. Weekly telephone surveillance ascertained acute morbidity symptoms in women and infants. We enrolled 784 pregnant women between October 2018 and March 2019. Of 784 women who enrolled, 736 (93.9%) delivered live births and 551 (70.3%) completed follow-up visits to 3 months postpartum. Arsenic was detected (≥0.02 μg/L) in 99.7% of water specimens collected from participants at enrolment. The medians (interquartile ranges) of water and urinary arsenic at enrolment were 5.1 (0.5, 25.1)μg/L and 33.1 (19.6, 56.5)μg/L, respectively. Water and urinary arsenic were strongly correlated (Spearman's ⍴=0.72) among women with water arsenic ≥ median but weakly correlated (⍴=0.17) among women with water arsenic < median. The PAIR Study is well positioned to examine the effects of low-moderate arsenic exposure and micronutrient deficiencies on immune outcomes in women and infants. NCT03930017.

A Pragmatic Randomized Feasibility Trial of Influenza Vaccines

BackgroundThe relative vaccine effectiveness (rVE) of high-dose quadrivalent influenza vaccines (QIV-HD) versus standard-dose quadrivalent influenza vaccines (QIV-SD) against hospitalizations and mortality in the general older population has not been evaluated in an individually randomized trial. Because of the large sample size required, such a trial will need to incorporate innovative, pragmatic elements.MethodsWe conducted a pragmatic, open-label, active-controlled, randomized feasibility trial in Danish citizens aged 65 to 79 years during the 2021–2022 influenza season. Participants were randomly assigned 1:1 to receive QIV-HD or QIV-SD. Randomization was integrated into routine vaccination practice, and the trial relied solely on nationwide administrative health registries for data collection. Outcomes consisted of a feasibility assessment and descriptive rVE estimates.ResultsWe invited 34,000 persons to participate. A total of 12,477 randomly assigned participants were included in the final analyses. Mean (±SD) age was 71.7±3.9 years, and 5877 (47.1%) were women. Registry-based data collection was feasible, with complete follow-up data for 99.9% of participants. Baseline characteristics were comparable to those of the overall Danish population aged 65 to 79 years. The incidence of hospitalization for influenza or pneumonia was 10 (0.2%) of 6245 in the QIV-HD group and 28 (0.4%) of 6232 in the QIV-SD group (rVE, 64.4%; 95% confidence interval, 24.4 to 84.6). All-cause death occurred in 21 (0.3%) and 41 (0.7%) participants in the QIV-HD and QIV-SD groups, respectively (rVE, 48.9%; 95% confidence interval, 11.5 to 71.3).ConclusionsConducting a pragmatic randomized trial of QIV-HD versus QIV-SD using existing infrastructure and registry-based data collection was feasible. The findings of lower incidence of hospitalization for influenza or pneumonia and all-cause mortality in the QIV-HD group compared with the QIV-SD group require replication in a future, fully powered trial. (Funded by Sanofi; ClinicalTrials.gov number, NCT05048589.)

A prospective cohort study on pregnancy outcomes in women immunized with seasonal quadrivalent influenza vaccine (QIV) during pregnancy

Influenza immunization rates in pregnancy remain below public health goals. This US based cohort study collected data on pregnancy outcomes and events of interest among women immunized with AFLURIA QUADRIVALENT® (QIV) during pregnancy, to compare to national data.

A Self-Emulsified Adjuvant System Containing the Immune Potentiator Alpha Tocopherol Induces Higher Neutralizing Antibody Responses than a Squalene-Only Emulsion When Evaluated with a Recombinant Cytomegalovirus (CMV) Pentamer Antigen in Mice.

The development of new vaccine adjuvants represents a key approach to improvingi the immune responses to recombinant vaccine antigens. Emulsion adjuvants, such as AS03 and MF59, in combination with influenza vaccines, have allowed antigen dose sparing, greater breadth of responses and fewer immunizations. It has been demonstrated previously that emulsion adjuvants can be prepared using a simple, low-shear process of self-emulsification (SE). The role of alpha tocopherol as an immune potentiator in emulsion adjuvants is clear from the success of AS03 in pandemic responses, both to influenza and COVID-19. Although it was a significant formulation challenge to include alpha tocopherol in an emulsion prepared by a low-shear process, the resultant self-emulsifying adjuvant system (SE-AS) showed a comparable effect to the established AS03 when used with a quadrivalent influenza vaccine (QIV). In this paper, we first optimized the SE-AS with alpha tocopherol to create SE-AS44, which allowed the emulsion to be sterile-filtered. Then, we compared the in vitro cell activation cytokine profile of SE-AS44 with the self-emulsifying adjuvant 160 (SEA160), a squalene-only adjuvant. In addition, we evaluated SE-AS44 and SEA160 competitively, in combination with a recombinant cytomegalovirus (CMV) pentamer antigen mouse.

Intradermal delivery of a quadrivalent cell-based seasonal influenza vaccine using an adjuvanted skin patch vaccination platform.

All seasonal influenza vaccines for 2021-2022 in the US were quadrivalent and the market continues to be dominated by intramuscular delivery of non-adjuvanted, virion-derived antigens grown in chicken eggs. Up to four new egg-adapted production influenza vaccine strains must be generated each year. The introduction in 2012 of Flucelvax®, which is grown in mammalian suspension cell culture and uses vaccine production strains without adaptive mutations for efficient growth in eggs, represented a major advance in vaccine production technology. Here we demonstrate that Flucelvax can be reformulated and combined with a liposomal adjuvant containing QS-21 (Verndari Adjuvant System 1.1, VAS1.1) or QS-21 and 3D-PHAD (VAS1.2) for intradermal administration using a painless skin patch, VaxiPatch™. VAS1.2 is similar to AS01B, the adjuvant system used in Shingrix® and Mosquirix™. We show that Flucelvax, when reformulated and concentrated using tangential flow filtration (TFF), maintains hemagglutination and single radial immunodiffusion (SRID) potency. Loading the reformulated Flucelvax material onto VaxiPatch arrays conferred high levels of resistance to heat stress and room temperature stability. TFF enriched vaccine antigens were combined with VAS1.1 or VAS1.2 and dispensed in 10nL drops into the pockets of 36 (total 360 nL) stainless steel microneedles arranged in a microarray 1.2cm in diameter. Using VaxiPatch delivery of 2µg of antigen, we demonstrated intramusuclar-comparable IgG and hemagglutination inhibition (HAI) immune responses in Sprague Dawley® rats. With addition of VAS1.2, antigen-specific IgG titers were increased as much as 68-fold (47-fold for VAS1.1) with improvements in seroconversion for three of four strains (all four were improved by VAS1.1). TFF-reformulated antigens combined with VAS1.1 or VAS1.2 and delivered by VaxiPatch showed only minor skin reactogenicity after 1h and no skin reactogenicity after 24h. These data indicate that VaxiPatch and the VAS system have the potential to be transformative for vaccine delivery.

Assessing the pyrogenicity of whole influenza virus particle vaccine in cynomolgus macaques.

Among inactivated influenza vaccines, the whole virus particle vaccine (WPV) elicits superior priming responses to split virus vaccine (SV) in efficiently inducing humoral and cellular immunity. However, there is concern for undesired adverse events such as fever for WPV due to its potent immunogenicity. Therefore, this study investigated the febrile response induced by subcutaneous injection with quadrivalent inactivated influenza vaccines of good manufacturing grade for pharmaceutical or investigational products in cynomolgus macaques. Body temperature was increased by 1°C-2°C for 6-12h after WPV administration at the first vaccination but not at the second shot, whereas SV did not affect body temperature at both points. Given the potent priming ability of WPV, WPV-induced fever may be attributed to immune responses that uniquely occur during priming. Since WPV-induced fever was blunted by pretreatment with indomethacin (a cyclooxygenase inhibitor), the febrile response by WPV is considered to depend on the increase in prostaglandins synthesized by cyclooxygenase. In addition, WPV, but not SV, induced the elevation of type I interferons and monocyte chemotactic protein 1 in the plasma; these factors may be responsible for pyrogenicity caused by WPV, as they can increase prostaglandins in the brain. Notably, sufficient antibody responses were acquired by half the amount of WPV without causing fever, suggesting that excessive immune responses to trigger the febrile response is not required for acquired immunity induction. Thus, we propose that WPV with a reduced antigen dose should be evaluated for potential clinical usage, especially in naïve populations.

REAL-WORLD EFFECTIVENESS ENHANCED INFLUENZA VACCINES IN OLDER ADULTS DURING THREE CONSECUTIVE INFLUENZA SEASONS: 2017–2020

Abstract Unenhanced influenza vaccines often fail to elicit adequate immune responses in adults ≥65 years due to immunosenescence. Enhanced influenza vaccines, MF59-adjuvanted trivalent inactivated influenza vaccine (aTIV) and high-dose vaccine (HD-TIV), were specifically developed to overcome this problem. The relative vaccine effectiveness (rVE) of aTIV vs HD-TIV and standard, egg-derived quadrivalent influenza vaccines (QIVe) was estimated in 3 retrospective cohort studies during the 2017-2020 US influenza seasons. Influenza-related medical encounters (IRMEs) were identified using diagnostic codes specific to influenza disease (ICD J09*-J11*) from a dataset that integrated electronic primary care medical records with pharmacy and medical claims. rVE was estimated using propensity score methods adjusting for variables including age, sex, race, ethnicity, geographic location, week of vaccination, frailty and health status. Subgroup analyses included specific age groups and those with high-risk medical conditions. aTIV demonstrated a consistent benefit over QIVe and HD-TIV across all three seasons in the overall study populations, and greater rVE versus QIVe was consistently observed over all three seasons in all age subgroups as well (65-74, 75-84, 85+). aIIV3 was comparable to HD-TIV and more effective than QIVe in a subgroup with high-risk medical conditions. These findings lend further support to the use of aTIV to prevent influenza-related medical encounters in older individuals.

505. Mucosal and Systemic Humoral Immunity Differences between Sexes during Influenza Vaccination and Viral Challenge

Abstract Background In previous influenza challenge studies we observed that the incidence of influenza symptoms was higher in women than in men, and that women experience more symptoms overall. Women also demonstrated lower neuraminidase (NA) inhibition (NAI) antibody titers than men after challenge and regression analysis suggested that NAI titers predict clinical outcomes. We sought to evaluate this using data from a more recent challenge study with more immunologically varied volunteers, while also assessing mucosal immunity. Methods We obtained mucosal and serum samples from healthy adults. Half underwent intramuscular quadrivalent influenza vaccination followed by influenza A (H1N1) intranasal challenge while others just challenge alone. Antibody titers and clinical outcomes between sexes were compared. Results No significant differences in shedding or symptom outcomes were observed between sexes. Similarly, no differences in systemic titers against NA or hemagglutinin (HA) were seen. Serum total IgG and IgA were also similar between sexes. Prior to vaccination, mucosal IgA titers were significantly lower against HA stalk and NA in women, but these differences disappeared after vaccination. In the unvaccinated group, lower nasal IgA titers were also seen in women pre-challenge. At 7 days post-challenge, differences in mucosal titers between sexes disappeared. However, at 56 days post-challenge, mucosal IgA titers against HA, HA stalk, and NA were all significantly lower in women. Conclusion In contrast to our previous findings, no differences in clinical outcomes or systemic NAI titers were observed between men and women, possibly due to differences in underlying immunity between study populations or the lower sample size in this study. However, mucosal differences were noted with women having lower mucosal titers than men against HA stalk and NA at baseline. While influenza vaccination and challenge eliminated differences in the short term, they reappeared 8 weeks after challenge, with all nasal IgA antibody titers (HA, HA stalk, and NA) lower in women. Further studies are necessary to understand the differences in influenza disease and immunity between sexes. Disclosures All Authors: No reported disclosures.

2139. Immunogenicity, reactogenicity and safety of a Respiratory Syncytial Virus prefusion F (RSVPreF3) candidate vaccine co-administered with the seasonal quadrivalent influenza vaccine in older adults

Abstract Background Respiratory syncytial virus (RSV) can cause severe respiratory disease in older adults (OAs). However, there is no approved vaccine against RSV disease in OAs. Co-administration of vaccines against RSV and influenza could be considered given their overlapping seasonality. Here, we assessed the immunogenicity, reactogenicity and safety of an RSV prefusion F Older Adult (RSVPreF3 OA) investigational vaccine when co-administered with the seasonal quadrivalent influenza vaccine (FLU-QIV) in OAs. Methods In this Phase 3, open-label, controlled, multi-country study (NCT04841577), OAs aged ≥ 60 years recruited in New Zealand, Panama and South Africa were randomized 1:1 to receive either RSVPreF3 OA and FLU-QIV simultaneously on day 1 (Co-Ad group), or FLU-QIV on day 1 and RSVPreF3 OA on day 31 (Control group). The co-primary objectives were to demonstrate the non-inferiority of i) RSVPreF3 OA in terms of RSV-A neutralizing antibody geometric mean titers (GMT) ratio and ii) FLU-QIV in terms of hemagglutinin inhibition antibody GMT ratio for each Flu strain when co-administered versus when administered alone. Blood samples were collected from all participants pre vaccination and 1 month post vaccination. Non-inferiority was demonstrated if the upper limit (UL) of the 95% confidence interval (CI) of the group GMT ratio (Control/Co-Ad) was ≤ 1.5. Secondary descriptive outcomes included reactogenicity and safety. Results 885 participants received at least 1 dose of the study interventions. Of these, 838 were included in the per protocol set at 1 month post vaccination. The demographic characteristics of the participants were similar across groups. The study co-primary objectives were met; for both vaccines, the UL of the 95% CI of the GMT ratio was ≤ 1.5 (Table 1). The observed safety events were balanced between Co-Ad and Control groups (Table 2). The reactogenicity profile of the Co-ad group compared with the Control group was driven by the RSVPreF3 OA investigational vaccine. Conclusion Our results support simultaneous seasonal vaccination with RSVPreF3 OA and FLU-QIV in adults ≥ 60 years, as co-administration elicits a statistically non-inferior immune response to the administration of each vaccine alone, with no safety concerns identified. Disclosures Nathali Montenegro, MD, GSK: Support for the present abstract/study Lorena Noriega-Aguirre, MD, ScD, Astra Zeneca: Advisor/Consultant|Astra Zeneca: Honoraria|Astra Zeneca: Support for attending meetings and/or travel|Boehringer Ingelheim: Honoraria|Boehringer Ingelheim: Support for attending meetings and/or travel|GSK: Advisor/Consultant|GSK: Support for the present abstract/study|Novartis: Honoraria Mohammed Bensellam, PhD, GlaxoSmithKline Biologicals SA: Agency worker on assignment at GSK Nathalie De Schrevel, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Ownership Interest Sherine Kuriyakose, MSc, GSK: GSK Employee Axel Lambert, MSc, GSK: GSK Employee Aurélie Olivier, PhD, GlaxoSmithKline Biologicals SA: I’m an employee of GSK Biologicals|GlaxoSmithKline Biologicals SA: Ownership Interest Veronica Hulstrøm, PhD MD, GlaxoSmithKline Biologicals SA: Employee.

Reducing Hospital Capacity Needs for Seasonal Respiratory Infections: The Case of Switching to High-Dose Influenza Vaccine for Dutch Older Adults

ObjectivesInfluenza is responsible for considerable health and economic burden every year. Especially older adults are vulnerable for influenza infection and its complications due to immunosenescence and often-underlying medical conditions. Recently, the innovative quadrivalent high-dose influenza vaccine (QIV-HD) has become available in Europe. Through its enhanced immunogenicity, QIV-HD offers improved protection for older adults against respiratory as well as cardiovascular complications. We estimated the potential impact—specifically in terms of hospital admissions and related costs—of a hypothetical past switch from QIV-Standard dose (SD) to QIV-HD in The Netherlands. MethodsEstimates of hospitalizations for the older adults vaccinated with QIV-SD were derived from the seasons 2010/2011-2017/2018. Subsequently, the number of respiratory infections and cardiovascular complications of influenza were estimated for the year 2019/2020 for both QIV-SD and QIV-HD. To calculate the overall corresponding savings, costs for hospital complications, derived from literature, were used. ResultsWhen QIV-HD would have been used instead of QIV-SD during the season 2019/2020, an additional 220 hospitalizations would have been averted among older adults of 60 years and older in the Netherlands. This corresponds to savings of €1 219 779 (uncertainty interval: 1 089 813-1 348 549), of which 69% is attributable to cardiovascular-related hospitalizations. ConclusionsWe demonstrate that a relevant improvement in influenza vaccination among older adults in The Netherlands can be achieved by switching from the current QIV-SD to QIV-HD. Not only comes a switch from QIV-SD to QIV-HD with a significant reduction in pressure on hospital capacity but also with notable cost savings.

Health Technology Assessment: a value-based tool for the evaluation of healthcare technologies. Reassessment of the cell-culture-derived quadrivalent influenza vaccine: Flucelvax Tetra® 2.0

Health Technology Assessment: a value-based tool for the evaluation of healthcare technologies. Reassessment of the cell-culture-derived quadrivalent influenza vaccine: Flucelvax Tetra® 2.0