Effectiveness of subunit influenza vaccination in the 2014–2015 season and residual effect of split vaccination in previous seasons

BackgroundIn Navarra, Spain, subunit vaccine was first used in the 2014–2015 season, whereas trivalent split-virion influenza vaccines had been used in previous seasons. We estimate the effectiveness of the subunit vaccine in the current season and split vaccine in the two previous seasons against laboratory-confirmed influenza in the 2014–2015 season.MethodsPatients with influenza-like illness hospitalized or attended by sentinel general practitioners were swabbed for influenza testing. The previous and current vaccine status of laboratory-confirmed cases was compared to test-negative controls.ResultsAmong 1213 patients tested, 619 (51%) were confirmed for influenza virus: 52% influenza A(H3N2), 46% influenza B, and 2% A(H1N1)pdm09. The overall effectiveness for subunit vaccination in the current season was 19% (95% confidence interval [CI]: −13 to 42), 2% (95%CI: −47 to 35) against influenza A(H3N2) and 32% (95%CI: −4 to 56) against influenza B. The effectiveness against any influenza was 67% (95%CI: 17–87) for 2012–2013 and 2013–2014 vaccination only, 42% (95%CI: −31 to 74) for 2014–2015 vaccination only, and 38% (95%CI: 8–58) for vaccination in the 2012–2013, 2013–2014 and 2014–2015 seasons. The same estimates against influenza A(H3N2) were 47% (95%CI: −60 to 82), −54% (95%CI: −274 to 37) and 28% (95%CI: −17 to 56), and against influenza B were 82% (95%CI: 19–96), 93% (95%CI: 45–99) and 43% (95%CI: 5–66), respectively.ConclusionThese results suggest a considerable residual protection of split vaccination in previous seasons, low overall effectiveness of current season subunit vaccination, and possible interference between current subunit and previous split vaccines.     

Ethanol promotes hydrolysis of 3H-labeled sialoconjugates from brain of mice in vitro

Acute administration of ethanol reportedly decreases total sialic acid in brain. Here, we tested the hypothesis in brain and liver that the decrement is due to increased hydrolysis of sialoglycoconjugates. Mouse tissue slices were pulse-labeled with N-[³H]acetyl-D-mannosamine, the precursor of sialic acid. Incorporation was linear for up to 4 hr of incubation. When the labeled slices were incubated with three concentrations of ethanol (0.1, 0.5, and 1 M) for 5 hr, labeled liver sialoconjugates were significantly affected only at 0.5 and 1 M ethanol, whereas labeled brain sialoconjugates were markedly decreased even at 100 mM ethanol. Sialidase activity decreased steadily with increasing concentration of ethanol, indicating that the increased hydrolysis was not attributable to an enhanced sialidase activity. n-Propanol and t-butanol had the same degradative effect as ethanol on sialocompounds; and 3 mM pyrazole, an inhibitor of alcohol dehydrogenase (ADH), had no effect on ethanol-induced degradation of sialocompounds. The protein/DNA ratio in liver showed a steady decrease with increasing ethanol. The data thus confirm the in vivo reports of ethanol-enhanced cleavage and rule out any increase in sialidase activity as a major cause.     

Can pneumococcal meningitis surveillance be used to assess the impact of pneumococcal conjugate vaccine on total invasive pneumococcal disease? A case-study from South Africa, 2005–2016

IntroductionSouth Africa introduced seven-valent pneumococcal conjugate vaccine (PCV7) in 2009 and PCV13 in 2011. We aimed to compare the estimated impact of PCV on pneumococcal meningitis (PM) to impact of PCV on total invasive pneumococcal disease (tIPD) based on risk reduction after PCV introduction.MethodsWe conducted national, laboratory-based surveillance for tIPD during 2005–2016. We estimated and compared rates of PCV13 and non-PCV13 serotype disease among tIPD and PM in individuals aged <5 years and ≥5 years, and compared these rates between the 2005–2008 pre-PCV introduction period and two time points after PCV introduction, 2012 and 2016.ResultsWe enrolled 45,853 tIPD cases; 17,251 (38%) were PM. By 2016, IPD caused by all serotypes decreased 55% (95%CI −57% to −53%) for tIPD, and 54% for PM (95%CI −58% to −51%), 0.7% difference between estimates (p = 0.7). No significant differences were observed between PCV7-serotype disease reduction in tIPD and PM in both age groups or the additional 6 serotypes included in PCV13 in <5 year olds in 2012 and 2016. In 2012 there was a significant difference between increases in non-PCV13 serotype disease in those ≥5 years for tIPD and PM (32% greater increase in PM, p < 0.001), but this difference was absent by 2016. There was a significant difference between the estimated decrease in additional PCV13 type disease in 2016 between tIPD and PM for those aged ≥5 years (28% greater reduction in PM, p = 0.008).ConclusionPM showed similar reductions to tIPD seven years after PCV introduction in vaccine serotype disease in those <5 years, and increases in non-vaccine serotype disease in all ages.     

Induced humoral immunity of different types of vaccines against most common variants of SARS-CoV-2 in Egypt prior to Omicron outbreak

The diversity of SARS-CoV-2 continues to lead to the emergence of new SARS-CoV-2 variants. SARS-CoV-2 antibody assays are crucial in managing the COVID-19 pandemic by determining the neutralizing antibody response. This study aims to investigate vaccine-induced antibodies against most common variants of SARS-CoV-2 in Egypt. Sera samples were collected from vaccinated participants and neutralizing activity against the SARS-CoV-2 variants was determined using microneutralization assay. Our results show that the BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCov-19 (AstraZeneca), and Ad26.COV2.S COVID-19 (Janssen) vaccines elicited neutralizing antibody responses more than the BBIBP-CorV vaccine (Sinopharm) against B.1, C.36.3, and AY.32 (Delta) variants. While vaccines remain highly effective in managing the COVID-19 pandemic, ongoing monitoring of vaccine effectiveness is needed.     

A cost-effectiveness analysis of South Africa’s seasonal influenza vaccination programme

BackgroundSeasonal influenza imposes a significant health and economic burden in South Africa, particularly in populations vulnerable to severe consequences of influenza. This study assesses the cost-effectiveness of South Africa’s seasonal influenza vaccination strategy, which involves vaccinating vulnerable populations with trivalent inactivated influenza vaccine (TIV) during routine facility visits. Vulnerable populations included in our analysis are persons aged ≥ 65 years; pregnant women; persons living with HIV/AIDS (PLWHA), persons of any age with underlying medical conditions (UMC) and children aged 6–59 months.MethodWe employed the World Health Organisation’s (WHO) Cost Effectiveness Tool for Seasonal Influenza Vaccination (CETSIV), a decision tree model, to evaluate the 2018 seasonal influenza vaccination campaign from a public healthcare provider and societal perspective. CETSIV was populated with existing country-specific demographic, epidemiologic and coverage data to estimate incremental cost-effectiveness ratios (ICERs) by comparing costs and benefits of the influenza vaccination programme to no vaccination.ResultsThe highest number of clinical events (influenza cases, outpatient visits, hospitalisation and deaths) were averted in PLWHA and persons with other UMCs. Using a cost-effectiveness threshold of US$ 3 400 per quality-adjusted life year (QALY), our findings suggest that the vaccination programme is cost-effective for all vulnerable populations except for children aged 6–59 months. ICERs ranged from ~US$ 1 750 /QALY in PLWHA to ~US$ 7 500/QALY in children. In probabilistic sensitivity analyses, the vaccination programme was cost-effective in pregnant women, PLWHA, persons with UMCs and persons aged ≥65 years in >80% of simulations. These findings were robust to changes in many model inputs but were most sensitive to uncertainty in estimates of influenza-associated illness burden.ConclusionSouth Africa's seasonal influenza vaccination strategy of opportunistically targeting vulnerable populations during routine visits is cost-effective. A budget impact analysis will be useful for supporting future expansions of the programme.     

Antibody response to tetravalent influenza subunit vaccine in patients infected with human immunodeficiency virus type 1

The capacity of patients infected with human immunodeficiency virus (HIV) to develop an adequate antibody response to influenza vaccination in relation to the CD4 cell count has been studied in a prospective study. A total of 73 subjects (54 HIV-infected patients and 19 healthy control persons) were vaccinated with influenza subunit vaccine containing 15 μg hemagglutinin of each of the following strains: A/Beijing/353/89(H3N2), A/Singapore/6/86(H1N1), B/Panama/45/90, and B/Beijing/1/87. Hemagglutinin inhibition (HI) antibody titers were determined prior to vaccination, 3 weeks afterwards, and at the end of the influenza season. The percentage of subjects with HI antibody titers above the assumed protective level was significantly lower in the HIV-infected patients for all 4 vaccine strains compared with those in the control group (7–26% and 42–74%, respectively). There was an association between CD4 cell count and antibody response to the B/Panama strain only. The serologic response to tetravalent subunit influenza vaccine is severely impaired in the majority of HIV-infected patients compared with control subjects. The results of this study challenges the recommendation to vaccinate HIV-infected patients.     

Clinician-parent discussions about influenza vaccination of children and their association with vaccine acceptance

ObjectiveTo examine how clinicians communicate with parents about influenza vaccination and the effect of these communication behaviors on parental vaccine decision-making.Study designWe performed a secondary analysis of data obtained from a cross-sectional observational study in which health supervision visits between pediatric clinicians and English-speaking parents of young children were videotaped. Eligible visits occurred during the 2011–2012 and 2013–2014 influenza seasons, included children ≥6 months, and contained an influenza vaccine discussion. A coding scheme of 10 communication behaviors was developed and applied to each visit. Associations between clinician communication behaviors and parental verbal vaccine acceptance and parental visit experience were examined using bivariate analysis and generalized linear mixed models.ResultsFifty visits involving 17 clinicians from 8 practices were included in analysis. The proportion of parents who accepted influenza vaccine was higher when clinicians initiated influenza vaccine recommendations using presumptive rather than participatory formats (94% vs. 28%, p < 0.001; adjusted odds ratio 48.2, 95% CI 3.5–670.5). Parental acceptance was also higher if clinicians pursued (vs. did not pursue) original recommendations when parents voiced initial resistance (80% vs. 13%, p < 0.05) or made recommendations for influenza vaccine concurrent with (vs. separate from) recommendations for other vaccines due at the visit (83% vs. 33%, p < 0.01). Parental visit experience did not differ significantly by clinician communication behaviors.ConclusionPresumptive initiation of influenza vaccine recommendations, pursuit in the face of resistance, and concurrent vaccine recommendations appear to increase parental acceptance of influenza vaccine without negatively affecting visit experience.     

Evaluation of T and B memory cell responses elicited by the pandemic H1N1 vaccine in HIV-infected and HIV-uninfected individuals

BackgroundThis study was to compare B and T memory cells elicited by a single dose monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009 H1N1) in HIV⁺ and HIV⁻ groups, and to analyze the impact of the prior seasonal vaccines to the immunogenicity of this vaccine.MethodsBlood samples were collected before vaccination (day 0) and at days 28 and 180. Participants were categorized into HIV⁻/LAIV, HIV⁻/TIV and HIV⁺/TIV subgroups according to the trivalent live-attenuated or inactivated (LAIV or TIV) seasonal influenza vaccines they received previously. The IgG⁺ memory B cells (B_Mem) and IFNγ⁺ T cells were measured against antigens including the H1N1 vaccine, the hemagglutinin (HA) and neuraminidase (NA) proteins or peptide pools of the pandemic and the seasonal H1N1 strains, respectively.ResultsOverall B_Mem responses increased significantly at day 28 but returned to baseline by day 180 in all three subgroups. The average frequency of the H1N1-specific B_Mem at day 28 for the HIV⁻/LAIV, HIV⁻/TIV and HIV⁺/TIV groups was 2.14%, 1.26% and 1.67%, respectively, and the average fold change was 14.39, 3.81 and 3.93, respectively. The differences of B_Mem between HIV⁻/LAIV and the two TIV subgroups were significant. For the IFNγ response, the overall spot counts ranged widely between 0 and 958/10⁶ PBMCs. The group average spot counts to H1N1 vaccine was 89, 102, and 30 at day 28 for HIV⁻/LAIV, HIV⁻/TIV and HIV⁺/TIV subgroups, respectively. The average increase of IFNγ response at day 28 vs day 0 in all three subgroups did not reach 2-fold.ConclusionParticipants with a prior LAIV seasonal vaccine, as compared to a TIV seasonal vaccine, responded significantly better to the monovalent H1N1 vaccine. Excluding LAIV participants, no difference was seen between the HIV⁺ and HIV⁻ subject groups in terms of B_Mem. The B_Mem response declined at 6 months.     

Infant antibody levels following 10-valent pneumococcal-protein D conjugate and DTaP-Hib vaccinations in the first year of life after maternal Tdap vaccination: An open-label,parallel, randomised controlled trial

BackgroundMaternal antibody levels after Tdap vaccination during pregnancy may affect infant primary antibody responses to pertussis, Tetanus toxoid (TT), Diphtheria toxoid (DT) vaccinations and pneumococcal vaccines with diphtheria toxin mutants like CRM197 as carrier protein.MethodsMothers were recruited in an open label randomised parallel controlled trial in 2014–2016 through midwifes. They received Tdap [Boostrix] at 30–32 weeks of pregnancy (n = 58) or within 48 h after delivery (n = 60). Infants received DTaP-IPV-Hib-HepB [Infanrix Hexa] and 10-valent protein D conjugated pneumococcal conjugate vaccine (PHiD-CV10 [Synflorix]) at age 3, 5 and 11 months. We now report on infant specific IgG levels towards DT, TT, Haemophilus influenzae type b polyribosylribitol phosphate (Hib PRP) and PHiD-CV10 before and after primary- and booster vaccination as secondary study endpoints; pertussis antibodies were the primary endpoint of the study. This trial is registered in clinicaltrialsregister.eu (EudraCT 2012–004006-9) and trialregister.nl (NTR number NTR4314).FindingsPost primary vaccinations, antibody levels to DT, but not TT, were significantly lower after Tdap vaccination during pregnancy compared to controls (GMC ratio 0.4, 95% CI 0.3–0.6 and 0.9, 95% CI 0.6–1.2, respectively). Antibodies to serotype 19F were significantly lower in the maternal Tdap group, whereas there were no differences in antibody levels to Hib PRP and the other 9 pneumococcal serotypes. Post booster vaccinations, no significant differences were observed, except for DT.InterpretationMaternal Tdap vaccination results in significant interference with infants responses not only to DT but also to conjugated pneumococcal vaccines containing DT mutants as carrier proteins. These interactions after maternal Tdap vaccination need to be taken into account when designing infants’ national immunization schedules and choice of vaccines.FundingThe Dutch Ministry of Health, Welfare and Sport.     

Predominance of influenza virus A(H3N2) 3C.2a1b and A(H1N1)pdm09 6B.1A5A genetic subclades in the WHO European Region, 2018–2019

BackgroundThe 2018/2019 influenza season in the WHO European Region was dominated by influenza A (H1N1)pdm09 and (H3N2) viruses, with very few influenza B viruses detected.MethodsCountries in the European Region reported virus characterization data to The European Surveillance System for weeks 40/2018 to 20/2019. These virus antigenic and genetic characterization and haemagglutinin (HA) sequence data were analysed to describe and assess circulating viruses relative to the 2018/2019 vaccine virus components for the northern hemisphere.ResultsThirty countries reported 4776 viruses characterized genetically and 3311 viruses antigenically. All genetically characterized A(H1N1)pdm09 viruses fell in subclade 6B.1A, of which 90% carried the amino acid substitution S183P in the HA gene. Antigenic data indicated that circulating A(H1N1)pdm09 viruses were similar to the 2018/2019 vaccine virus. Genetic data showed that A(H3N2) viruses mostly fell in clade 3C.2a (75%) and 90% of which were subclade 3C.2a1b. A lower proportion fell in clade 3C.3a (23%) and were antigenically distinct from the vaccine virus. All B/Victoria viruses belonged to clade 1A; 30% carried a double amino acid deletion in HA and were genetically and antigenically similar to the vaccine virus component, while 55% carried a triple amino acid deletion or no deletion in HA; these were antigenically distinct from each other and from the vaccine component. All B/Yamagata viruses belonged to clade 3 and were antigenically similar to the virus component in the quadrivalent vaccine for 2018/2019.ConclusionsA simultaneous circulation of genetically and antigenically diverse A(H3N2) and B/Victoria viruses was observed and represented a challenge to vaccine strain selection.