Delivery Of Influenza Vaccine Research Articles

Orally dissolving film as a potential vaccine delivery carrier to prevent influenza virus infection

Orally dissolving films (ODF) are designed to be dissolved on the tongue and absorbed in the mouth. It offers multiple advantages over the commonly used needle-based vaccines, especially in terms of convenience allowing safe, painless, and easy self-administration. As the efficacy of ODF-encapsulated influenza vaccines has not been demonstrated, we assessed the protection elicited by inactivated influenza virus (A/PR/8/34, H1N1) vaccine delivered using ODFs in mice. Trehalose and pullulan components of the ODF ensured that the HA antigens of the inactivated PR8 virus retained their stability while ensuring the rapid release of the vaccines upon exposure to murine saliva. Mice were immunized thrice by placing the PR8-ODF on the tongues of mice at 4-week intervals, and vaccine-induced protection was evaluated upon lethal homologous challenge infection. The PR8-ODF vaccination elicited virus-specific serum IgG and IgA antibody responses, hemagglutinin inhibition (HAI), and viral neutralization. Upon challenge infection, ODF vaccination showed higher levels of IgG and IgA antibody responses in the lungs and antibody-secreting cell (ASC) responses in both lung and spleen compared to unimmunized controls. These results corresponded with the enhanced T cell and germinal center B cell responses in the lungs and spleens. Importantly, ODF vaccination significantly reduced lung virus titers and inflammatory cytokines (IFN-γ, IL-6) production compared to unvaccinated control. ODF vaccination ensured 100% survival and prevented weight loss in mice. These findings suggest that influenza vaccine delivery through ODFs could be a promising approach for oral vaccine development.

Immune cell receptor-specific nanoparticles as a potent adjuvant for nasal split influenza vaccine delivery

Mucosal delivery systems have gained much attention as effective way for antigen delivery that induces both systemic and mucosal immunity. However, mucosal vaccination faces the challenges of mucus barrier and effective antigen uptake and presentation. In particular, split, subunit and recombinant protein vaccines that do not have an intact pathogen structure lack the efficiency to stimulate mucosal immunity. In this study, poly (lactic acid-co-glycolic acid-polyethylene glycol) (PLGA-PEG) block copolymers were modified by mannose to form a PLGA-PEG-Man conjugate (mannose modified PLGA-PEG), which were characterized. The novel nanoparticles (NPs) prepared with this material had a particle size of about 150 nm and a zeta potential of −15 mV, and possessed ideal mucus permeability, immune cell targeting, stability and low toxicity. Finally, PLGA-PEG-Man nanoparticles (PLGA-PEG-Man NPs) were successfully applied for intranasal delivery of split influenza vaccine in rat for the first time, which triggered strong systemic and mucosal immune responses. These studies suggest that PLGA-PEG-Man NPs could function as competitive potential nano-adjuvants to address the challenge of inefficient mucosal delivery of non-allopathogenic antigens.

Costs of seasonal influenza vaccine delivery in a pediatric demonstration project for children aged 6–23 months — Nakuru and Mombasa Counties, Kenya, 2019–2021

BackgroundDuring November 2019–October 2021, a pediatric influenza vaccination demonstration project was conducted in four sub-counties in Kenya. The demonstration piloted two different delivery strategies: year-round vaccination and a four-month vaccination campaign. Our objective was to compare the costs of both delivery strategies. MethodsCost data were collected using standardized questionnaires and extracted from government and project accounting records. We reported total costs and costs per vaccine dose administered by delivery strategy from the Kenyan government perspective in 2021 US$. Costs were separated into financial costs (monetary expenditures) and economic costs (financial costs plus the value of existing resources). We also separated costs by administrative level (national, regional, county, sub-county, and health facility) and program activity (advocacy and social mobilization; training; distribution, storage, and waste management; service delivery; monitoring; and supervision). ResultsThe total estimated cost of the pediatric influenza demonstration project was US$ 225,269 (financial) and US$ 326,691 (economic) for the year-round delivery strategy (30,397 vaccine doses administered), compared with US$ 214,753 (financial) and US$ 242,385 (economic) for the campaign strategy (25,404 doses administered). Vaccine purchase represented the largest proportion of costs for both strategies. Excluding vaccine purchase, the cost per dose administered was US$ 1.58 (financial) and US$ 5.84 (economic) for the year-round strategy and US$ 2.89 (financial) and US$ 4.56 (economic) for the campaign strategy. ConclusionsThe financial cost per dose was 83% higher for the campaign strategy than the year-round strategy due to larger expenditures for advocacy and social mobilization, training, and hiring of surge staff for service delivery. However, the economic cost per dose was more comparable for both strategies (year-round 22% higher than campaign), balanced by higher costs of operating equipment and monitoring activities for the year-round strategy. These delivery cost data provide real-world evidence to inform pediatric influenza vaccine introduction in Kenya.

Time lapses between distribution of influenza vaccines to health authorities and their administration by General Practitioners (GPs) to older adults: a retrospective study over five influenza seasons in Italy

ABSTRACTBackgroundDelays in influenza vaccine delivery and administration can hinder vaccine coverage and protection. This study examines the differentials in distributing and administering adjuvanted trivalent (aTIV) and quadrivalent influenza vaccines (aQIV) to older adults in Italy’s primary care setting and its potential impact on hospitalization risk over 5 epidemic seasons.MethodsUsing a primary care database, individuals aged ≥ 65 years were selected. The proportion of vaccine distribution to regional authorities and subsequent administration by GPs was estimated using census data. Using quantile (median) regression, we examined the relationship between velocities of vaccine distribution and administration (doses/week) and the incidence of hospitalizations.ResultsOver the 5 influenza seasons, the velocity of distribution and administration of aTIV/aQIV ranged 341–833 and 152–270 median doses/week; no trend was yielded for the difference between these velocities (p = 0.189) or vaccine coverage (p = 0.142). An association was observed for each differential dose/week between distributed and administered vaccines and all-cause hospitalizations with a 10% increase in 2017–2018, 54% in 2018–2019, and 12% in 2020–2021 season.ConclusionsThese findings highlight the importance of minimizing the time lapse between vaccine distribution and administration to mitigate the impact of influenza and address factors that contribute to vaccination barriers.

Prolonging the delivery of influenza virus vaccine improves the quantity and quality of the induced immune responses in mice.

Influenza vaccines play a vital role in protecting individuals from influenza virus infection and severe illness. However, current influenza vaccines have suboptimal efficacy, which is further reduced in cases where the vaccine strains do not match the circulating strains. One strategy to enhance the efficacy of influenza vaccines is by extended antigen delivery, thereby mimicking the antigen kinetics of a natural infection. Prolonging antigen availability was shown to quantitatively enhance influenza virus-specific immune responses but how it affects the quality of the induced immune response is unknown. Therefore, the current study aimed to investigate whether prolongation of the delivery of influenza vaccine improves the quality of the induced immune responses over that induced by prime-boost immunization. Mice were given daily doses of whole inactivated influenza virus vaccine for periods of 14, 21, or 28 days; the control group received prime-boost immunization with a 28 days interval. Our data show that the highest levels of cellular and humoral immune responses were induced by 28 days of extended antigen delivery, followed by 21, and 14 days of delivery, and prime-boost immunization. Moreover, prolonging vaccine delivery also improved the quality of the induced antibody response, as indicated by higher level of high avidity antibodies, a balanced IgG subclass profile, and a higher level of cross-reactive antibodies. Our findings contribute to a better understanding of the immune response to influenza vaccination and have important implications for the design and development of future slow-release influenza vaccines.

Salmonella-Delivered COBRA-HA1 Antigen Derived from H1N1 Hemagglutinin Sequences Elicits Broad-Spectrum Protection Against Influenza A Subtypes

A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza vaccines. In this study, a strategy called computationally optimized broadly reactive antigen (COBRA) was used to generate a consensus sequence of the hemagglutinin globular head portion (HA1) of influenza virus samples collected from 1918 to 2021 to trace evolutionary changes and incorporate them into the designed constructs. Constructs carrying different HA1 regions were delivered into eukaryotic cells by Salmonella-mediated bactofection using a Semliki Forest virus RNA-dependent RNA polymerase (RdRp)-based eukaryotic expression system, pJHL204. Recombinant protein expression was confirmed by Western blot and immunofluorescence assays. Mice immunized with the designed constructs produced a humoral response, with a significant increase in immunoglobulin G (IgG) levels, and a cell-mediated immune response, including a 1.5-fold increase in CD4+ and CD8+ T cells. Specifically, constructs #1 and #5 increased the production of interferon-γ (IFN-γ) producing CD4+ and CD8+ T cells, skewing the response toward the T helper type 1 cell (Th1) pathway. Additionally, interleukin-4 (IL-4)-producing T cells were upregulated 4-fold. Protective efficacy was demonstrated, with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer > 40 against the selected viral strains. The designed constructs conferred a broadly protective immune response, resulting in a notable reduction in viral titer and minimal inflammation in the lungs of mice challenged with the influenza A/PR8/34, A/Brisbane/59/2007, A/California/07/2009, KBPV VR-92, and NCCP 43021 strains. This discovery revolutionizes influenza vaccine design and delivery; Salmonella-mediated COBRA-HA1 is a highly effective in vivo antigen presentation strategy. This approach can effectively combat seasonal H1N1 influenza strains and potential pandemic outbreaks.

Rapid determination of influenza vaccine potency by an SPR-based method using subtype or lineage-specific monoclonal antibodies.

Potency testing and release of annual influenza vaccines require preparation, calibration, and distribution of reference antigens (RAs) and antisera every year, which takes an average of 8 to 12 weeks, and can be a major limiting factor in pandemic situations. Here we describe for the first time a robust Surface Plasmon Resonance (SPR)-based method that employs influenza subtype or lineage hemagglutinin (HA) specific monoclonal antibodies (mAbs) to measure the HA concentration in influenza multivalent vaccines. Implementing such an advanced test method will at the very least eliminate the rate-limiting and laborious efforts of making antisera reagents annually, and thus expedite the influenza vaccine delivery to the public by at least 6 weeks. Results demonstrate that the SPR-based method, developed using Biacore, is robust and not influenced by the type of RAs (inactivated whole virus, split, or subunit vaccine-derived materials), whether they are used as monovalent or multivalent preparations. HA concentrations obtained for monovalent drug substances (DS) or quadrivalent drug products (DP) of inactivated influenza split vaccine showed a tight correlation (the best fit value for the slope is 1.001 with R2 of 0.9815 and P-value <0.0001) with the corresponding values obtained by the current potency assay, Single Radial Immunodiffusion (SRID). Supplementary analysis of the results by the Bland-Altman plot demonstrated good agreement between the SPR and SRID methods, with no consistent bias of the SPR versus SRID method. We further demonstrate that the SPR-based method can be used to estimate HA concentrations in intermediates of the influenza vaccine manufacturing process containing varying matrices and impurity levels. Further, the results demonstrate that the method is sensitive to detecting degradation of HA caused by elevated temperature, low pH, and freezing. It is evident from this report and other published work that the advancement of analytical techniques and the early findings are encouraging for the implementation of alternate potency assays with far-reaching benefits covering both seasonal and pandemic influenza.

Seasonal influenza vaccination in the Americas: Progress and challenges during the COVID-19 pandemic

BackgroundVaccination is one of the most effective measures to prevent influenza illness and its complications; influenza vaccination remained important during the COVID-19 pandemic to prevent additional burden on health systems strained by COVID-19 demand. ObjectivesWe describe policies, coverage, and progress of seasonal influenza vaccination programs in the Americas during 2019–2021 and discuss challenges in monitoring and maintaining influenza vaccination coverage among target groups during the COVID-19 pandemic. MethodsWe used data on influenza vaccination policies and vaccination coverage reported by countries/territories via the electronic Joint Reporting Form on Immunization (eJRF) for 2019–2021. We also summarized country vaccination strategies shared with PAHO. ResultsAs of 2021, 39 (89 %) out of 44 reporting countries/territories in the Americas had policies for seasonal influenza vaccination. Countries/territories adapted health services and immunization delivery strategies using innovative approaches, such as new vaccination sites and expanded schedules, to ensure continuation of influenza vaccination during the COVID-19 pandemic. However, among countries/territories that reported data to eJRF in both 2019 and 2021, median coverage decreased; the percentage point decrease was 21 % (IQR = 0–38 %; n = 13) for healthcare workers, 10 % (IQR = -1.5–38 %; n = 12) for older adults, 21 % (IQR = 5–31 %; n = 13) for pregnant women, 13 % (IQR = 4.8–20.8 %; n = 8) for persons with chronic diseases, and 9 % (IQR = 3–27 %; n = 15) for children. ConclusionsCountries/territories in the Americas successfully adapted influenza vaccination delivery to continue vaccination services during the COVID-19 pandemic; however, reported influenza vaccination coverage decreased from 2019 to 2021. Reversing declines in vaccination will necessitate strategic approaches that prioritize sustainable vaccination programs across the life course. Efforts should be made to improve the completeness and quality of administrative coverage data. Lessons learned from COVID-19 vaccination, such as the rapid development of electronic vaccination registries and digital certificates, might facilitate advances in coverage estimation.

Quillaja brasiliensis nanoparticle adjuvant formulation improves the efficacy of an inactivated trivalent influenza vaccine in mice.

The threat of viral influenza infections has sparked research efforts to develop vaccines that can induce broadly protective immunity with safe adjuvants that trigger robust immune responses. Here, we demonstrate that subcutaneous or intranasal delivery of a seasonal trivalent influenza vaccine (TIV) adjuvanted with the Quillaja brasiliensis saponin-based nanoparticle (IMXQB) increases the potency of TIV. The adjuvanted vaccine (TIV-IMXQB) elicited high levels of IgG2a and IgG1 antibodies with virus-neutralizing capacity and improved serum hemagglutination inhibition titers. The cellular immune response induced by TIV-IMXQB suggests the presence of a mixed Th1/Th2 cytokine profile, antibody-secreting cells (ASCs) skewed toward an IgG2a phenotype, a positive delayed-type hypersensitivity (DTH) response, and effector CD4+ and CD8+ T cells. After challenge, viral titers in the lungs were significantly lower in animals receiving TIV-IMXQB than in those inoculated with TIV alone. Most notably, mice vaccinated intranasally with TIV-IMXQB and challenged with a lethal dose of influenza virus were fully protected against weight loss and lung virus replication, with no mortality, whereas, among animals vaccinated with TIV alone, the mortality rate was 75%. These findings demonstrate that TIV-IMXQB improved the immune responses to TIV, and, unlike the commercial vaccine, conferred full protection against influenza challenge.

Non-invasive transcutaneous influenza immunization using vaccine-loaded vaterite particles.

Transcutaneous immunization receives much attention due to the recognition of a complex network of immunoregulatory cells in various layers of the skin. The elaboration of non-invasive needle-free approaches towards antigen delivery holds especially great potential here while searching for a hygienically optimal vaccination strategy. Here, we report on a novel protocol for transfollicular immunization aiming at delivery of an inactivated influenza vaccine to perifollicular antigen presenting cells without disrupting the stratum corneum integrity. Porous calcium carbonate (vaterite) submicron carriers and sonophoresis were utilized for this purpose. Transportation of the vaccine-loaded particles into hair follicles of mice was assessed in vivo via optical coherence tomography monitoring. The effectiveness of the designed immunization protocol was further demonstrated in an animal model by means of micro-neutralization and enzyme-linked immunosorbent assays. The titers of secreted virus-specific IgGs were compared to those obtained in response to intramuscular immunization using conventional influenza vaccine formulation demonstrating no statistically significant differences in antibody levels between the groups. The findings of our pilot study render the intra-follicular delivery of the inactivated influenza vaccine by means of vaterite carriers a promising alternative to invasive immunization.

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.

Australian hospital paediatricians and nurses' perspectives and practices for influenza vaccine delivery in children with medical comorbidities.

Influenza vaccination of children with medical comorbidities is critical due their increased risks for severe influenza disease. In Australia, hospitals are an avenue for influenza vaccine delivery to children with comorbidities but are not always effectively utilised. Qualitative enquiry sought to ascertainment the barriers and enablers for influenza vaccination recommendation, delivery, and recording of these children at Australian hospitals. Semi-structured interviews and discussion group sessions were conducted with paediatricians and nurses at four tertiary paediatric specialist hospitals and two general community hospitals in three Australian states. Transcripts from interviews and group sessions were inductively analysed for themes. The Capability, Opportunity, Motivation, and Behaviour (COM-B) model was used to explore the elements of each theme and identify potential interventions to increase influenza vaccination recommendation and delivery behaviours by providers. Fifteen discussion sessions with 28 paediatricians and 26 nurses, and nine in-depth interviews (five paediatricians and four nurses) were conducted. Two central thematic domains were identified: 1. The interaction between hospital staff and parents/patients for influenza vaccine recommendation, and 2. Vaccination delivery and recording in the hospital environment. Six themes across these domains emerged detailing the importance of dedicated immunisation services, hospital leadership, paediatricians' vaccine recommendation role, the impact of comorbidities, vaccination recording, and cocooning vaccinations. Supportive hospital leadership, engaged providers, and dedicated immunisation services were identified as essential for influenza vaccination of children with comorbidities in Australian hospital. Recommendation of influenza vaccination for Australian children with comorbidities is impacted by the beliefs of paediatricians and the perceived impact of influenza disease on children's comorbidities. Dedicated immunisation services and supportive hospital leadership were drivers for influenza vaccine delivery at hospitals. Future interventions targeting hospital-based influenza vaccine delivery for children with comorbidities should take a rounded approach targeting providers' attitudes, the hospital environment and leadership support.

Development of a road map to scale up the uptake and utilization of influenza vaccine in 22 countries of Eastern Mediterranean Region

BackgroundThe aim of this project was to develop a road map to support countries in Eastern Mediterranean Region in developing and implementing evidence-based seasonal influenza vaccination policy, strengthen influenza vaccination delivery program and address vaccine misperceptions and hesitancy. MethodsThe road map was developed through consultative meetings with countries’ focal points, review of relevant literature and policy documents and analysis of WHO/UNICEF Joint Reporting Form on immunization ((JRF 2015–2020) data. Countries were categorised into three groups, based on the existence of influenza vaccination policy and national regulatory authority, availability of influenza vaccine in the country and number of influenza vaccine doses distributed/ 1000 population. The final road map was shared with representatives of all countries in Eastern Mediterranean Region and other stakeholders during a meeting in September 2021. ResultThe goal for next 5 years is to increase access to and use of utilization of seasonal influenza vaccine in Eastern Mediterranean Region to reduce influenza-associated morbidity and mortality among priority groups for vaccination. Countries in the Eastern Mediterranean Region are at different stages of implementation of the influenza vaccination program, so activities are planned under four strategic priority areas based on current situations in countries. The consultative body recommended that some countries should establish a new seasonal influenza vaccination programme and ensure the availability of vaccines, while other countries need to reduce vaccine hesitancy and enhance current seasonal influenza vaccination coverage, particularly in all high-risk groups. Countries are also encouraged to leverage COVID-19 adult vaccination programs to improve seasonal influenza vaccine uptake. ConclusionThis road map was developed through a consultative process to scale up the uptake and utilization of influenza vaccine in all countries of Eastern Mediterranean Region. The road map proposes activities that should be adopted in the local context to develop/ update national policies and programs.

“Every interaction you have …should be an opportunity to discuss and offer influenza vaccination”. Health service perspectives on influenza vaccination promotion and delivery to Aboriginal families living in New South Wales, Australia

IntroductionThere is little research to understand reasons for suboptimal influenza vaccination uptake among Aboriginal people of different ages in Australia. This study aimed to better understand the communication needs and preferences of Aboriginal families (Phase 2) in New South Wales, Australia, and their health service providers (Phase 1), to inform future interventions to improve influenza immunisation coverage in Aboriginal communities. This paper reports from Phase 1 of the study. Material and methodsAboriginal and non-Aboriginal researchers designed and conducted the study, with cultural governance provided by Aboriginal health care professionals and other community members working within health departments or community healthcare settings across Australia. In Phase 1 we conducted interviews and focus groups with 18 Aboriginal immunisation providers and mainstream immunisation co-ordinators from three geographic areas in New South Wales. We used group-based thematic analysis with a cultural lens and sought participants’ feedback prior to finalising results. ResultsWe identified four themes, framed as opportunities for improvement: better supporting Aboriginal Medical Services as providers of influenza vaccinations; improving the accessibility and appropriateness of mainstream services for Aboriginal families; improving health providers’ knowledge of Aboriginal people’ influenza risk and their willingness to recommend vaccination; and engaging communities to design influenza vaccination resources. ConclusionsTo achieve optimal influenza vaccination coverage, all health services must take responsibility for providing culturally responsive clinical care to Aboriginal families. We suggest that, where possible, mainstream services incorporate elements of the family-centred and broader model of health used by Aboriginal Medical Services. This includes creating a welcoming environment, appropriately identifying and getting to know Aboriginal patients, taking a preventative approach, and opportunistically offering and strongly encouraging influenza vaccination to the individual and their family.

Views and experiences of maternal healthcare providers regarding influenza vaccine during pregnancy globally: A systematic review and qualitative evidence synthesis.

The World Health Organization (WHO) recommends that pregnant women receive influenza vaccination; however, uptake of the vaccine remains low. Maternity health care professionals (MHCPs) play an important role in motivating pregnant women to receive the influenza vaccine. However, factors such as MHCPs' views and knowledge about the vaccine, and time constraints due to workload may influence MHCPs' practices and opinions about women receiving the influenza vaccine during pregnancy. To date, the qualitative evidence exploring MHCPs' views and experiences around influenza vaccine uptake in pregnant women has not been synthesised. To systematically review and thematically synthesise qualitative evidence that explores the views and experiences of MHCPs involved in the provision of the maternal influenza vaccine worldwide. Five databases (MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science) were searched, supplemented with searches of included paper reference lists and grey literature. Study selection was conducted by up to three researchers applying pre-specified inclusion/exclusion criteria. Quality assessment was undertaken, data were extracted, coded and synthesised to develop descriptive and analytical themes. Eight studies involving 277 participants were included. Seventeen descriptive themes were interpreted, embedded within six analytical themes. MHCPs perceived that maternal influenza vaccination delivery can be facilitated by trusting relationships, good communication, knowledge about the vaccine leading to confidence in recommending vaccine, electronic vaccination prompts, and presence of national guidelines. However, workload, time constraints, MHCP's perception of pregnant women's concerns, and social/cultural/environmental influences could prevent the likelihood of delivery of influenza vaccine. Knowledgeable MHCPs who were regularly updated about vaccination based on scientific evidence were more confident when discussing and recommending the influenza vaccine to pregnant women. In addition, the presence of national policies and guidelines and electronic prompts for maternal influenza vaccination would enhance the delivery of the vaccine. Our findings suggest that approaches to enhance the vaccination uptake rate in pregnant women include addressing MHCPs barriers to discussing influenza vaccination through education, sufficient time for discussions, and electronic prompts about vaccination, as well as evidence based local and national guidelines.

Nano/microparticle Formulations for Universal Influenza Vaccines

Influenza affects millions of people worldwide and can result in severe sickness and even death. The best method of prevention is vaccination; however, the seasonal influenza vaccine often suffers from low efficacy and requires yearly vaccination due to changes in strain and viral mutations. More conserved universal influenza antigens like M2 ectodomain (M2e) and the stalk region of hemagglutinin (HA stalk) have been used clinically but often suffer from low antigenicity. To increase antigenicity, universal antigens have been formulated using nano/microparticles as vaccine carriers against influenza. Utilizing polymers, liposomes, metal, and protein-based particles, indicators of immunity and protection in mouse, pig, ferrets, and chicken models of influenza have been shown. In this review, seasonal and universal influenza vaccine formulations comprised of these materials including their physiochemical properties, fabrication, characterization, and biologic responses in vivo are highlighted. The review is concluded with future perspectives for nano/microparticles as carrier systems and other considerations within the universal influenza vaccine delivery landscape. Graphical

Influenza and pneumococcal vaccination delivery in older Hispanic populations in the United States.

National reports suggest that Hispanic patients may underutilize influenza and pneumococcal vaccination, although studies sometimes conflict on this point. A clearer picture of adult immunization utilization in older Hispanic patients is necessary to ensure equity in adult vaccinations. Using electronic health records from 648 community health centers (CHCs) across 21 states, we compared English-preferring Hispanic patients, Spanish-preferring Hispanic patients, and Non-Hispanic White (NHW) adults aged ≥50 years across five outcomes between 2012-2017: (1) Odds of ever receiving pneumococcal vaccination after age 65, (2) Odds of ever receiving ≥2 pneumococcal vaccinations for those ≥65, (3) odds of vaccination between the ages of 50 and 64 for those with diabetes or heart disease, (4) odds of influenza vaccine, and (5) annual rate of influenza vaccination. Of our total study sample (N=143,869), 85,562 were age 50-64 during the entire study period, and 65,977 were ≥65 at some point during the study period. In patients aged 50-64, Spanish-preferring Hispanic patients were more likely to have ever had an influenza vaccination (covariate-adjusted odds ratio [aOR]=1.33, 95% CI=1.29-1.37), had higher rates of annual influenza vaccination (covariate-adjusted rate ratio [aRR]=1.41, 95% CI=1.38-1.44), and higher odds of pneumococcal vaccination (aOR=1.87, 95% CI=1.76-1.98) than NHW patients. These findings were similar in Spanish-preferring Hispanic patients ≥65. English-preferring Hispanics ≥65 were less likely than NHW patients to ever have an influenza vaccination (aOR=0.91, 95% CI=0.85-0.98) and to have ever received at least one (aOR=0.92, 95% CI=0.86-0.99) or two (aOR=0.86, 95% CI=0.77-0.95) pneumococcal vaccine doses. In a multistate CHC network, Spanish-preferring Hispanic patients were more likely to receive influenza and pneumococcal vaccinations than NHW patients; older English-preferring Hispanic patients were often less likely than NHW patients to receive these vaccinations. In vaccine initiatives, English-preferring Hispanic patients may be at higher risk of vaccination inequity.

Identifying Practices to Promote Inpatient Adolescent and Influenza Vaccine Delivery.

Many hospitalized children are underimmunized. We assessed the association between hospital immunization practices and tetanus, diphtheria, and acellular pertussis (Tdap), meningococcal, human papillomavirus (HPV), and influenza vaccine delivery. An electronic survey regarding hospital vaccine delivery practices was distributed via the Pediatric Health Information System (PHIS) and Pediatric Research in Inpatient Settings networks to PHIS hospitals. Number of vaccines delivered and total discharges in 2018 were obtained from the PHIS database to determine hospital vaccine delivery rates; patients 11 to 18 years old (adolescent vaccines) and 6 months to 18 years old (influenza vaccine) were included. Vaccine delivery rates were risk adjusted by using generalized linear mixed-effects modeling and compared with survey responses to determine associations between the number or presence of specific practices and vaccine delivery. Adjusted HPV and meningococcal vaccine delivery rates could not be calculated because of low delivery. Twenty-nine hospitals completed a survey (57%). 152 499 and 423 046 patient encounters were included for the adolescent and influenza vaccines, respectively. Unadjusted inpatient vaccine delivery rates varied. After adjustment, the number of practices was associated only with influenza vaccine delivery (P = .02). Visual prompts (P = .02), nurse or pharmacist ordering (P = .003), and quality improvement projects (P = .048) were associated with increased influenza vaccine delivery; nurse or pharmacist ordering had the greatest impact. No practices were associated with Tdap vaccine delivery. The number and presence of specific hospital practices may impact influenza vaccine delivery. Further research is needed to identify strategies to augment inpatient adolescent immunization.

Influenza Vaccination in Massachusetts Jails: A Mixed-Methods Analysis.

Influenza infects millions of people each year and contributes to tens of thousands of deaths annually despite the availability of vaccines. People most at risk of influenza complications are disproportionately represented in people incarcerated in US prisons and jails. The objectives of this study were to survey health administrators in Massachusetts county jails about institutional influenza vaccine policies and practices and estimate influenza vaccination rates in Massachusetts jails from 2013 to 2020. In April 2020, we administered surveys to the health services administrators in Massachusetts' 14 county jails to gather information about influenza vaccination policies and delivery practices. To calculate influenza vaccination rates for each facility, we obtained data on influenza vaccine orders from the Massachusetts Department of Public Health for each county in Massachusetts for influenza seasons 2013-2020. We calculated summary statistics for each reporting facility and each year, conducted a Kruskal-Wallis analysis to compare vaccination rates between years, and used a linear regression model to identify predictors of vaccination rates. Influenza vaccination rates in Massachusetts jails ranged from 1.9% to 11.8%. We found no significant differences in vaccination rates between years. Influenza vaccine ordering and delivery practices varied by jail, and respondents had high levels of confidence in influenza policies and vaccine delivery practices. Influenza vaccination rates in Massachusetts jails are low, and delivery practices in jails vary. Lack of influenza vaccinations in jails is a gap in health care that needs to be prioritized, especially considering the current COVID-19 pandemic. Further investigations for effective and equitable vaccination in this population should involve people who are incarcerated and people who make influenza vaccine policies in jails.

Transforming the vaccine supply chain in Australia: Opportunities and challenges

BackgroundAnalyzing potential benefits of thermostable vaccines delivered through Micro Array Patch (MAP) has received great attention in low and middle-income countries. The experience may or may not be the same in developed countries where the infrastructure is more developed. It is anticipated that transforming the vaccine supply chain from syringe-and-needle to thermostable MAP-delivered vaccines will result in reduced supply chain costs – including manufacturing/supply, logistics/distribution, and administration costs – as well as reduced wastes and improved safety. This paper provides an end-to-end supply chain analysis comparing the key aspects (cost, safety and environmental aspects) of the conventional syringe-and-needle vaccine supply chain with those of the MAP vaccine supply chain for influenza vaccine delivery in Australia. Directions for future research in this area will be provided. ObjectiveTo determine the potential supply chain impacts of replacing syringe-and-needle flu vaccine with MAP-enabled thermostable flu vaccine in Australia. MethodsWe analyze the current flu vaccine supply chain in Australia to identify practical limitations and opportunities for improvement. Data/information is collected through interviewing the key stakeholders across vaccine supply chain including vaccine manufacturers, logistics providers, clinics, hospitals, and pharmacies. FindingsA detailed practice-informed analysis is completed on the key operations of the flu vaccine supply chain. Barriers and limitations of the conventional flu vaccine are discussed, along with potential improvements that can be achieved through the implementation of MAP-enabled flu vaccine delivery. We discuss how technology-driven innovations can help advance vaccine supply chains, improve vaccine visibility, reduce wastes, and enable informed decision-making. ConclusionWe find that the benefits of moving from syringe-and-needle vaccines to thermostable MAP-delivered vaccines are beyond transportation and storage cost saving. Potential benefits through cost saving, waste reduction, and service level improvement are discussed along with various safety and wellbeing consequences followed by directions for future research in this area.