A real-world study evaluating the relative vaccine effectiveness of a cell-based quadrivalent influenza vaccine compared to egg-based quadrivalent influenza vaccine in the US during the 2017–18 influenza season

BackgroundCell-based influenza vaccine manufacturing reduces egg adaptations that can decrease vaccine effectiveness. We evaluated the relative vaccine effectiveness (rVE) of cell-based quadrivalent influenza vaccine (QIVc) compared to standard-dose egg-based quadrivalent influenza vaccines (QIVe-SD) against influenza-related and serious respiratory events among subjects 4–64 years of age during the 2017–18 influenza season.MethodsA retrospective cohort analysis was conducted using administrative claims data in the US (IQVIA PharMetrics Plus® database). Subjects vaccinated with QIVc or QIVe-SD from 8/2017–1/2018 were identified (date of vaccination termed the index date). Influenza-related hospitalizations/ER visits, all-cause hospitalizations and serious respiratory hospitalizations/ER visits were assessed post-vaccination. Inverse probability of treatment weighting (IPTW) and Poisson regression were used to evaluate the adjusted rVE of QIVc compared to QIVe-SD. In a subgroup analysis, rVE was assessed for several subgroups of interest (4–17, 18–64 and 50–64 years, and subjects with ≥1 high-risk condition). In a secondary economic analysis, annualized all-cause costs over the follow-up were compared using propensity score matching (PSM) and generalized estimating equation (GEE) models.ResultsThe study sample comprised 555,538 QIVc recipients and 2,528,524 QIVe-SD recipients. Prior to adjustment, QIVc subjects were older and had higher total costs in the 6-months pre-index. Following IPTW-adjustment and Poisson regression, QIVc was more effective in reducing influenza-related hospitalizations/ER visits, all-cause hospitalizations, and hospitalizations/ER visits related to asthma/COPD/bronchial events and other respiratory events compared to QIVe-SD. Similar trends were generally observed in the subgroup analysis. Following PSM adjustment and GEE regression, QIVe-SD was associated with significantly higher annualized all-cause total costs compared to QIVc, driven by higher costs for outpatient medical services and inpatient hospitalizations.ConclusionsAfter adjustment for confounders and selection bias, QIVc reduced influenza-related hospitalizations/ER visits, all-cause hospitalizations, and serious respiratory hospitalizations/ER visits compared to QIVe-SD. QIVc was associated with significantly lower all-cause total costs.     

Does pneumococcal vaccine reduce influenza morbidity in humans?

A retrospective study was conducted to verify the possibility that people immunized with pneumococcal vaccine (PV) show lower morbidity not only for pneumonia but also for influenza. A total of 450 individuals were enrolled between 1999 and 2003 and allocated to one of the following groups: (A) not vaccinated; (B) immunized with PV during 1999; (C) immunized with anti-influenza vaccine (Flu-V) each year; and (D) immunized with PV once in 1999 and Flu-V every consecutive year. People from group B showed significantly lower percentage of influenza-related diseases during the year 2000 in comparison with those from group A (p<0.01), whereas in the course of 2001 the morbidity of patients from group B was lower compared with the other groups (p<0.01). The results point to a way to decrease the morbidity of influenza-related diseases by immunization with PV only, at least for 2-3 years, avoiding Flu-V administration and permitting considerable saving for health care providers. Therefore, it is concluded that PV can reduce the morbidity of influenza at a greater rate than the Flu-V.     

Effectiveness of inactivated influenza vaccine in children by vaccine dose, 2013–18

ObjectivesWe assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses.MethodsVE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed.ResultsIn the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 [95% CI, 0.505–0.621], 0.550 [95% CI, 0.516–0.586]), 0.549 [95% CI, 0.517–0.583], and 1.014 [95% CI, 0.907–1.135], for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1–12 years, especially among those aged 1–5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A.ConclusionsBoth one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.     

Seasonal influenza vaccine effectiveness against influenza in 2012–2013: A hospital-based case-control study in Lithuania

Background

Due to scarce information on seasonal influenza vaccine effectiveness (SIVE) against severe clinical influenza outcomes in risk populations, we conducted a case-control study to assess its effects against laboratory-confirmed influenza in hospitalized patients during the 2012–2013 influenza season.

Methods

We conducted a test-negative case-control study among ≥18 years old patients with influenza-like illness (ILI) hospitalized in two Lithuanian hospitals. Cases were influenza A(H1N1), A(H3) or influenza B positive by RT-PCR, and controls were influenza negative. Additional demographic and clinical data to assess the role of confounding were collected. SIVE and its confidence intervals (95% CI) were estimated by using multivariate logistic regression as (1 − OR) × 100%.

Results

The sample consisted of 185 subjects. Seasonal influenza vaccine uptake was 5%. Among 111 (60%) influenza positive cases, 24.3% were A(H1N1), 10.8% were A(H3) and 24.3% were influenza B cases. Unadjusted SIVE was 79% (95% CI −6% to 96%) and after the adjustment it increased to 86% (95% CI 19% to 97%).

Conclusions

Seasonal influenza vaccination in 2012–2013 was associated with reduced occurrence of laboratory-confirmed influenza, but due to low sample size the estimate of SIVE is imprecise. Given high prevalence of influenza in hospitalized ILI cases and low influenza vaccination coverage, there is a need to increase influenza vaccination rates.     

The faces of influenza vaccine recommendation: A Literature review of the determinants and barriers to health providers’ recommendation of influenza vaccine in pregnancy

IntroductionWHO recommends influenza vaccination for pregnant women and health providers (HPs), yet global uptake for both is persistently low. Research suggests that HPs greatly influence uptake of influenza vaccine in pregnant women. Our review studies HPs’ recommendation of influenza vaccine to pregnant women, determinants and barriers to recommendation, and the role that HPs may play in global influenza vaccine coverage.MethodsWe undertook a comprehensive global review of literature relating to HPs’ recommendation of seasonal influenza vaccines to pregnant women and the determinants and barriers to recommendation and how this may vary by country and context. We evaluated data from each study including frequency of HP recommendation, vaccine coverage, determinants and barriers to recommendation, and the odds of recommending. We tracked the frequency of determinants and barriers to recommendation in heat maps and organized data by world regions and income classifications.ResultsFrom 32 studies in 15 countries, we identified 68 determinants or barriers to HPs’ recommendation. Recommendation rates were highest (77%) in the Americas and lowest in South East Asia (18%). A HP’s own influenza vaccine status was a main determinant of recommendation in multiple country contexts and from different provider types. Financial barriers to recommendation were present in higher-income countries and policy-related barriers were highlighted in lower-income countries. HP perceptions of safety, efficacy, and the utility of vaccine were the most frequently cited barriers, relevant in almost every context.ConclusionsHP recommendation is important to influenza vaccine implementation in pregnant women. A HP’s own status is an important recommendation determinant in multiple contexts. Vaccine program implementation plans should consider the impact of HPs' knowledge, awareness and vaccine confidence on their own uptake and recommendation practices, as well as on the uptake among pregnant women. Addressing safety and efficacy concerns is relevant in all contexts for HPs and pregnant women.     

Why is influenza vaccine uptake so low among Aboriginal adults?

Objectives: Determine major barriers to, and facilitators of, influenza vaccination of Aboriginal adults, in order to improve coverage from the current level of 30%. Methods: i) A focus group with 13 Aboriginal Immunisation Healthcare Workers; and ii) a cross‐sectional survey of Aboriginal people aged ≥18 years at the 2017 New South Wales Koori Knockout (29 September–2 October). Results: The focus group nominated poor identification of Aboriginality in general practice. Of 273 survey respondents, a substantial minority (30%) were unaware of their eligibility for free influenza vaccination. More than half (52%) believed the vaccine could cause influenza, 40% reported there were better ways than vaccination for avoiding infection and 30% said they would not have the vaccine if it was offered to them. Regarding health service access, few reported experiencing difficulty (17%), feeling uncomfortable (15%) or being discriminated against (8%), but 53% reported not receiving a reminder from a health professional. Conclusions: Misconceptions about influenza disease and vaccine among Aboriginal people and inadequate identification of Aboriginality in general practice appear to be the greatest barriers to vaccination, rather than health service access in general. Implications for public health: More active communication to and targeting of Aboriginal adults is required; this is even more urgent following the arrival of COVID‐19.     

Comparison of vaccine effectiveness against influenza hospitalization of cell-based and egg-based influenza vaccines, 2017–2018

Egg-based influenza vaccines could be less effective than cell-based vaccine due to adaptive mutations acquired for growth. We conducted a test-negative case-control study at Kaiser Permanente Southern California to assess vaccine effectiveness (VE) against hospitalization for laboratory-confirmed influenza during 2017–2018. Among the 1186 cases and 6946 controls, 74% and 59%, respectively, were ages ≥ 65 years. For any influenza, the adjusted relative VE of cell-based vaccine versus egg-based vaccines was 43% (95% CI: −45% to 77%) for patients ages < 65 years and 6% (95% CI: −46% to 39%) for patients ages ≥ 65 years. For influenza A(H3N2), the adjusted relative VE was 61% (95% CI: −63% to 91%) for patients ages < 65 years and −4% (95% CI: −70% to 37%) for patients ages ≥ 65 years. Statistically significant protection against influenza hospitalization of cell-based vaccine compared to egg-based vaccines was not observed, but further studies in additional influenza seasons are warranted.     

Intranasal hydroxypropyl-β-cyclodextrin-adjuvanted influenza vaccine protects against sub-heterologous virus infection

Intranasal vaccination with inactivated influenza viral antigens is an attractive and valid alternative to currently available influenza (flu) vaccines; many of which seem to need efficient and safe adjuvant, however. In this study, we examined whether hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used pharmaceutical excipient to improve solubility and drug delivery, can act as a mucosal adjuvant for intranasal flu vaccines. We found that intranasal immunization of mice with hemagglutinin split- as well as inactivated whole-virion influenza vaccine with HP-β-CD resulted in secretion of antigen-specific IgA and IgGs in the airway mucosa and the serum as well. As a result, both HP-β-CD adjuvanted-flu intranasal vaccine protected mice against lethal challenge with influenza virus, equivalent to those induced by experimental cholera toxin-adjuvanted ones. Of note, intranasal use of HP-β-CD as an adjuvant induced significantly lower antigen-specific IgE responses than that induced by aluminum salt adjuvant. These results suggest that HP-β-CD may be a potent mucosal adjuvant for seasonal and pandemic influenza vaccine.     

Development of a live-attenuated influenza B ΔNS1 intranasal vaccine candidate

We discovered a unique, single amino acid mutation in the influenza B M1 protein promoting viral growth of NS1 truncation mutants in Vero cells. Due to this mutation, we were able to generate an influenza B virus lacking the complete NS1 open reading frame (ΔNS1-B virus) by reverse genetics, which was growing to titers of 8 log₁₀ TCID₅₀/ml in a Vero cell culture-based micro-carrier fermenter. The ΔNS1-B vaccine candidate was attenuated in IFN-competent hosts such as human alveolar epithelial cells (A549) similar to influenza A ΔNS1 viruses. In ferrets, the ΔNS1-B virus was replication-deficient and did not provoke any clinical symptoms. Importantly, a single intranasal immunization of ferrets at a dose as low as 6 log₁₀ TCID₅₀/animal induced a significant HAI response and provided protection against challenge with wild-type influenza B virus. So far, the lack of a ΔNS1-B virus component growing to high titers in cell culture has been limiting the possibility to formulate a trivalent vaccine based on deletion of the NS1 gene. Our study closes this gap and paves the way for the clinical evaluation of a seasonal, trivalent, live replication-deficient ΔNS1 intranasal influenza vaccine.     

Why do not patients receive influenza vaccine in December and January?

BACKGROUND: Influenza vaccination levels in older patients have changed little since the mid-1990s. Despite frequent health care visits by a majority of older persons, many missed opportunities continue to occur. METHODS: Patients were eligible for the study if they were age 50 and older, had not received influenza vaccine during the current season and were making a scheduled visit to one of the 13 study sites in California, New York, or New Mexico for purposes other than vaccination. Through direct observation, we determined if office staff inquired about vaccination status, discussed vaccination, or both. We defined missed opportunities as failure to administer influenza vaccine to patients for whom it was indicated. RESULTS: Missed opportunities increased steadily from October to January (P < 0.0001), and were more common when there was no inquiry or discussion (P < 0.00001), among patients aged 50-64 (P < 0.0001) and in California and New Mexico (P = 0.001). A classification tree analysis revealed that lack of inquiry and week of visit contributed most to missed opportunities. DISCUSSION: Early in the vaccination season, missed opportunities were uncommon and specific inquiries into or discussion of vaccination did not appear necessary. In December and January, patients tended to be vaccinated only when vaccination was addressed during the visit. Efforts to remind patients about vaccination later in the vaccination season may be essential to achieving higher coverage in the U.S.     

Three-season effectiveness of inactivated influenza vaccine in preventing influenza illness and hospitalization in children in Japan, 2013–2016

ObjectivesWe assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children 6 months to 15 years of age in 2015/16 season. In addition, based on the data obtained during the three seasons from 2013 to 2016, we estimated the three-season VE in preventing influenza illness and hospitalization.MethodsOur study was conducted according to a test-negative case-control design (TNCC) and as a case-control study based on influenza rapid diagnostic test results.ResultsDuring 2015/16 season, the quadrivalent IIV was first used in Japan. The adjusted VE in preventing influenza illness was 49% (95% confidence interval [CI]: 42–55%) against any type of influenza, 57% (95% CI: 50–63%) against influenza A and 34% (95% CI: 23–44%) against influenza B. The 3-season adjusted VE was 45% (95% CI: 41–49%) against influenza virus infection overall (N = 12,888), 51% (95% CI: 47–55%) against influenza A (N = 10,410), and 32% (95% CI: 24–38%) against influenza B (N = 9232). An analysis by age groups showed low or no significant VE in infants or adolescents. By contrast, VE was highest in the young group (1–5 years old) and declined with age thereafter. The 3-season adjusted VE in preventing hospitalization as determined in a case-control study was 52% (95% CI: 42–60%) for influenza A and 28% (95% CI: 4–46%) for influenza B, and by TNCC design, it was 54% (95% CI: 41–65%) for influenza A and 34% (95% CI: 6–54%) for influenza B.ConclusionWe demonstrated not only VE in preventing illness, but also VE in preventing hospitalization based on much larger numbers of children than previous studies.     

Seasonal influenza vaccine coverage among high-risk populations in Thailand, 2010–2012

BackgroundThe Advisory Committee on Immunization Practice of Thailand prioritizes seasonal influenza vaccinations for populations who are at highest risk for serious complications (pregnant women, children 6 months–2 years, persons ≥65 years, persons with chronic diseases, obese persons), and healthcare personnel and poultry cullers. The Thailand government purchases seasonal influenza vaccine for these groups. We assessed vaccination coverage among high-risk groups in Thailand from 2010 to 2012.MethodsNational records on persons who received publicly purchased vaccines from 2010 to 2012 were analyzed by high-risk category. Denominator data from multiple sources were compared to calculate coverage. Vaccine coverage was defined as the proportion of individuals in each category who received the vaccine. Vaccine wastage was defined as the proportion of publicly purchased vaccines that were not used.ResultsFrom 2010 to 2012, 8.18 million influenza vaccines were publicly purchased (range, 2.37–3.29 million doses/year), and vaccine purchases increased 39% over these years. Vaccine wastage was 9.5%. Approximately 5.7 million (77%) vaccine doses were administered to persons ≥65 years and persons with chronic diseases, 1.4 million (19%) to healthcare personnel/poultry cullers, 82,570 (1.1%) to children 6 months–2 years, 78,885 (1.1%) to obese persons, 26,481 (0.4%) to mentally disabled persons, and 17,787 (0.2%) to pregnant women. Between 2010 and 2012, coverage increased among persons with chronic diseases (8.6% versus 14%; p < 0.01) and persons ≥65 years (12%, versus 20%; p < 0.01); however, coverage decreased for mentally disabled persons (6.1% versus 4.9%; p < 0.01), children 6 months–2 years (2.3% versus 0.9%; p < 0.01), pregnant women (1.1% versus 0.9%; p < 0.01), and obese persons (0.2% versus 0.1%; p < 0.01).ConclusionsFrom 2010 to 2012, the availability of publicly purchased vaccines increased. While coverage remained low for all target groups, coverage was highest among persons ≥65 years and persons with chronic diseases. Annual coverage assessments are necessary to promote higher coverage among high-risk groups in Thailand.     

Who gets hospitalized for influenza pneumonia in Thailand? Implications for vaccine policy

Risk factor information for severe complications of interpandemic influenza is needed to inform vaccine policy in Thailand. We identified patients with lab-confirmed influenza who were hospitalized with pneumonia during September 2003 to August 2004. Among the 80 case-patients identified through a population-based pneumonia surveillance system in eastern Thailand, cases were 6.2 and 11.1 times more likely to be among persons<1 year old and >75 years old, respectively, compared with the overall population. Cases were also 7.6 times more likely to have chronic respiratory disease. In Thailand, the young, elderly, and those with chronic disease were at high risk for hospitalized pneumonia from influenza.     

Do parents prefer inactivated or live attenuated influenza vaccine for their children?

ObjectivesTo determine the proportion of children whose parents prefer them to receive live, attenuated influenza vaccine (LAIV) or inactivated influenza vaccine (IIV), examine reasons for preferences, and determine what percentage of vaccinated children receive other than the preferred type of vaccine and why.MethodsParental-reported data for the 2014–15 and 2015–16 influenza seasons from the National Immunization Survey-Flu (NIS-Flu), a random-digit-dialed, dual frame (landline and cellular telephone) survey of households with children, were analyzed. We calculated the proportions of vaccinated children aged 2–17 years whose parents preferred LAIV, IIV, or had no preference, and the proportions that were vaccinated with other than the preferred type of vaccine.ResultsFor the 2014–15 and 2015–16 seasons, 55.2% and 53.7%, respectively, of vaccinated children had parents who reported no preference for either IIV or LAIV. The percentage who preferred LAIV was 22.7% and 21.7%, and IIV was 22.1% and 24.7%. The most common reason given by parents for preferring LAIV was the child’s fear of needles (70.9%) and for preferring IIV was belief that the shot is more effective (29.0%). Approximately one-third of vaccinated children whose parents preferred LAIV received IIV only.ConclusionsThe main finding of this study was that most parents do not have a vaccine type preference for their children. The lack of overwhelming preference is advantageous for the maintenance of vaccination coverage levels during times when one vaccine type is not available or not recommended such as in the 2016–17 and 2017–18 seasons when there was a temporary recommendation not to administer LAIV.