北京地区2005～2006年流感病原监测结果与乙型流感病毒HA1序列分析

目的：分析2005～2006年冬春季北京地区流感病原监测及乙型流感病毒种系分布情况。方法：采用狗肾传代细胞（MDCK）和鸡胚培养分离流感病毒，经血清学试验鉴定分型。选取部分乙型流感提取病毒RNA，经RT—PCR扩增得到HA1基因片段并进行核苷酸序列测定，用信息软件进行种系发生树分析。结果：共采集流感样病例标本1874份，经MDCK细胞分离到510株流感病毒。其中H1N1亚型244株（47．84％）；H3N2亚型57株（11．18％）；B型209株（40．98％），208株为Victoria系，1株为Yamagata系。对210份细胞分离阳性标本进行鸡胚培养，共分离到流感病毒9株，全部为H1N1亚型。28株B型优势流行株与当年疫苗株不属于同一谱系，相差较远；与新预测（2006～2007年）的疫苗株亲缘关系最近。结论：北京地区2005～2006年冬春季节存在H1N1、H3N2、B型3种流感病毒流行，以H1N1、B型为优势毒株。B型Victoria系优势株正在通过变异逐步在流行中占据主导地位。新预测流感疫苗可对人群产生良好的保护效果。     

Safety and immunogenicity of a seasonal quadrivalent influenza vaccine (GC3110A) in healthy participants aged ≥ 65 years

BackgroundSeasonal Influenza is still considered associated with seasonal morbidity and hospitalization in the elderly population. The World Health Organization (WHO) recommended seasonal quadrivalent influenza vaccine (QIV) to reduce burden of two currently circulating influenza B lineages. Until 2019 Korean National Immunization Program (NIP) recommended trivalent influenza vaccine (TIV) after ongoing debates on cost effectiveness of QIV for elderly population. Although influenza vaccine only showed modest effect on reducing influenza in elderly, this study aimed to evaluate the immunogenicity and safety of inactivated QIV in healthy participants ≥ 65 years of age.MethodsA total of 274 healthy participants aged ≥ 65 years received a QIV. Seroconversion-based vaccine efficacy of 4 strains of seasonal influenza was assessed 21 days after vaccination and adverse events were monitored until 180 days after vaccination.ResultsThe percentages of participants seroconverted after vaccination on HI antibody against each strain were 36.5% (99/271) to A/H1N1, 47.6% (129/271) to A/H3N2, 40.6% (110/271) to B Yamagata, and 49.1% (133/271) to B Victoria. The percentages of participants seroprotected after vaccination on HI antibody against each strain were 81.2% (220/271) to A/H1N1, 98.5% (267/271) to A/H3N2, 95.2% (258/271) to B Yamagata, and 93.7% (254/271) to B Victoria. There was no serious adverse event (SAE) related with the study vaccine.ConclusionThe quadrivalent split influenza vaccine is expected to offer seroprotection against influenza A and both influenza B lineages even in the elderly population.     

Factors associated with humoral immune response in older adults who received egg-free influenza vaccine

BackgroundImmune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults.MethodsCommunity-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018–2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen.ResultsAmong 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1).ConclusionOverall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed.     

Influenza vaccine effectiveness against laboratory-confirmed influenza in a vaccine-mismatched influenza B-dominant season

BackgroundThe 2017–2018 influenza season in Israel was characterized by the predominance of influenza B Yamagata, with a lesser circulation of influenza A(H1N1)pdm09 and influenza A(H3N2). We estimated vaccine effectiveness (VE) of the inactivated influenza vaccine which was selected for use that season.MethodsEnd-of-season VE and 95% confidence intervals (CI) against laboratory-confirmed influenza-like illness (ILI) were estimated by means of the test-negative design. Age-specific VE analysis was carried out using a moving age interval.ResultsSpecimen were obtained from 1,453 community ILI patients; 610 (42.0%) were influenza-positive, among which 69.7% were B, 17.2% A(H1N1)pdm09 and 13.4% A(H3N2). A 98.6% of molecularly characterized influenza B belonged to the Yamagata lineage. Of the sampled individuals, 1320 were suitable for VE analysis. Of those vaccinated, 90.6% received the inactivated trivalent influenza vaccine (TIV) containing a Victoria lineage influenza B-like virus. VE against influenza A differed by age, with the highest VE of 72.9% (95%CI 31.9–89.2%) observed in children 0.5–14 years old, while all ages VE was 46.6% (95%CI 10.4–68.2%). All ages VE against influenza B was 23.2% (95%CI −10.1–46.4%) with age-specific analysis showing non-significant VE estimates. Utilizing a moving age interval of 15 years, afforded a detailed age-specific insight into influenza VE against the influenza viruses circulating during the 2017–2018 season.ConclusionsThe moderate-high 2017–2018 influenza A VE among children and adolescents, supports seasonal influenza vaccination at a young age. The low VE against influenza B in Israel, is most likely the result of influenza B/TIV-mismatch.     

Effectiveness of seasonal influenza vaccine in Australia, 2015: An epidemiological,antigenic and phylogenetic assessment

BackgroundA record number of laboratory-confirmed influenza cases were notified in Australia in 2015, during which type A(H3) and type B Victoria and Yamagata lineages co-circulated. We estimated effectiveness of the 2015 inactivated seasonal influenza vaccine against specific virus lineages and clades.MethodsThree sentinel general practitioner networks conduct surveillance for laboratory-confirmed influenza amongst patients presenting with influenza-like illness in Australia. Data from the networks were pooled to estimate vaccine effectiveness (VE) for seasonal trivalent influenza vaccine in Australia in 2015 using the case test-negative study design.ResultsThere were 2443 eligible patients included in the study, of which 857 (35%) were influenza-positive. Thirty-three and 19% of controls and cases respectively were reported as vaccinated. Adjusted VE against all influenza was 54% (95% CI: 42, 63). Antigenic characterisation data suggested good match between vaccine and circulating strains of A(H3); however VE for A(H3) was low at 44% (95% CI: 21, 60). Phylogenetic analysis indicated most circulating viruses were from clade 3C.2a, rather than the clade included in the vaccine (3C.3a). VE point estimates were higher against B/Yamagata lineage influenza (71%; 95% CI: 57, 80) than B/Victoria (42%, 95% CI: 13, 61), and in younger people.ConclusionsOverall seasonal vaccine was protective against influenza infection in Australia in 2015. Higher VE against the B/Yamagata lineage included in the trivalent vaccine suggests that more widespread use of quadrivalent vaccine could have improved overall effectiveness of influenza vaccine. Genetic characterisation suggested lower VE against A(H3) influenza was due to clade mismatch of vaccine and circulating viruses.     

An influenza B outbreak during the 2007/2008 winter among appropriately immunized elderly people living in a nursing home

The study evaluated the immunogenicity and efficacy of a trivalent subunit MF59-adjuvanted influenza vaccine (A/Wisconsin/67/05 (H3N2), A/Solomon Islands/3/06 (H1N1) and B/Malaysia/2506/04) in preventing serologically diagnosed infections in a group of 67 institutionalized elderly volunteers during 2007/2008 winter, characterized by co-circulation of drifted A/H3N2, A/H1N1 and B influenza viruses. Influenza vaccination induced a significant increase in the amounts of hemagglutination inhibiting antibodies, both against the vaccine and the epidemic drifted strains. However, vaccination did not prevent the circulation of the new drifted influenza B virus (B/Florida/4/06-like), belonging to the B/Yamagata/16/88-lineage, antigenically and genetically distinct from B/Victoria/2/87-lineage viruses from which the vaccine B strain was derived.     

2007-2008年齐齐哈尔市流感监测结果分析

[目的]监测流感流行趋势,了解流感流行优势株。[方法]对齐齐哈尔市2007～2008年流感监测资料进行分析。[结果]2家哨点测医院2007年10月至2008年3月合计报告流感样病例2956例,占同期门急诊就诊病例总数75153例的3．93％。全市未发生流感暴发疫情,实验室收到并检测302份ILI标本,分离出19株流感病毒（分离率为6．29％）。其中,A（H1N1）亚型2株,A（H3N2）亚型10株,B型Yamagata系6株,B型Victoria系1株。[结论]2007～2008年度齐齐哈尔市流感呈散发状态,分离的流感毒株主要是H3N2和B／Yamagata。     

2014 - 2017年淮安市流感监测结果分析

目的 分析淮安市2014 - 2017年流感的流行特征,为该地区流感防控工作提供科学依据。方法 对淮安市2014 - 2017年的流感样病例报告、病原学检测和流感/流感样病例暴发疫情等数据进行描述和分析。结果 淮安市2014 - 2017年2家流感监测哨点医院共报告ILI总数60 176例,平均ILI%为4.11%,2014 - 2016年ILI%水平保持在较稳定的水平（2%～3%）,2017年大幅提高至7.97%;ILI年龄构成以15岁以下低年龄组为主,占88.06%;共采集咽拭子8 458份,总阳性检出率为10.57%,其中A(H3N2)型384份（42.95%）、新A(H1N1)型153份（17.11%）、B(Yamagata)型211份（23.60%）、B(Victoria)型146份（16.33%）,各亚型在不同季节交替流行;A(H3N2)型在各年龄组中占比均最高;新A(H1N1)型在＜5岁组中占比最高（20.39%）,B(Yamagata)型在5～14岁组中占比最高（30.00%）,B(Victoria)型在＞60岁组占比最高（28.57%）;共报告流感样病例暴发疫情18起,均发生在中小学校。结论 淮安市2014 - 2016年流感流行强度较平稳,2017年有大幅提高。今后的监测需严防可能出现的流感病毒新亚型,重点保护15岁以下易感人群,加强学校等人群聚集性场所的暴发疫情监测。     

Molecular epidemiology and genetic characterization of influenza B virus in Lebanon during 2016–2018

BackgroundInfluenza B viruses are a major cause of serious acute respiratory infections in humans.MethodsNasopharyngeal swabs were collected from subjects with influenza-like illness during October 2016–June 2018 and screened for influenza A and B. The hemagglutinin (HA) and neuraminidase (NA) genes of the Lebanese influenza B specimens were sequenced and phylogenetically compared with the vaccine strains and specimens from the Eastern Mediterranean Region and Europe.ResultsInfluenza A and B viruses co-circulated between October and May and peaked between January and March. During the 2016–2017 season, A/H3N2 (33.4%) and B/Yamagata (29.7%) were the predominantly circulating viruses followed by B/Victoria and A/H1N1pdm09 viruses. During the 2017–2018 season, A/H3N2 (31.5%) and A/H1Npdm09 (29.3%) were most prevalent with co-circulation of B/Yamagata and to a lesser extent B/Victoria viruses. The B/Yamagata specimens belonged to clade-3 while the B/Victoria belonged to clade-1A. None of the analyzed specimens had a mutation known to confer resistance to NA inhibitors (NAIs).ConclusionMultiple subtypes of influenza co-circulate each year in Lebanon with a peak between January and March. The trivalent vaccine included a B/Victoria strain which mismatched the B/Yamagata lineage that predominated during the study period, highlighting the importance of quadrivalent vaccines.     

Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through <18 years of age: A randomized controlled phase II dose-finding trial

Quadrivalent high-dose inactivated influenza vaccine (Fluzone® High-Dose Quadrivalent, IIV4-HD) was licensed in the USA in 2019 for adults ≥ 65 years of age. This Phase II study examined safety and immunogenicity of 3 dose formulations of IIV4-HD in healthy children. In a randomized, modified double-blind, active-controlled trial in the USA and Canada, 661 children aged 6 months through < 18 years received 1 or 2 doses intramuscularly of standard-dose quadrivalent influenza vaccine (IIV4-SD; 15 µg HA/strain), IIV4-HD at 3 dose levels (30, 45, and 60 µg HA/strain), or adjuvanted trivalent influenza vaccine (aIIV3, 7.5 µg HA/strain). Rates of unsolicited AEs were similar irrespective of dose. No treatment-related serious adverse events or deaths were reported. Reactogenicity was slightly higher for IIV4-HD than IIV4-SD, although most solicited reactions were grade 1 or 2. Hemagglutination inhibition (HAI) and seroneutralization antibody titers were measured 28–35 days after each dose. Geometric mean HAI titers increased with increasing hemagglutinin dose, especially in children 6 months through < 3 years. For IIV4-HD 60 µg, in participants 6 months through < 18 years of age, the geometric mean titer ratio (95% confidence interval) versus IIV4-SD was 1.35 (0.94, 1.94) for A/H1N1, 2.51 (1.77, 3.55) for A/H3N2, 1.60 (1.17, 2.18) for B/Victoria, and 1.51 (1.13, 2.03) for B/Yamagata. The GMT ratio (95% confidence interval) for IIV4-HD 60 µg versus IIV4-SD was highest for participants 6 months through < 3 years of age: 4.24 (2.05, 8.76) for A/H1N1, 3.14 (1.53, 6.44) for A/H3N2, 2.04 (1.10, 3.77) for B/Victoria, and 1.92 (1.08, 3.41) for B/Yamagata; similarly, seroneutralization antibody GMT ratio was highest in these participants: 170 (84.6, 340) for A/H1N1, 7.13 (4.90, 10.4) for A/H3N2, 35.8 (22.1, 58.1) for B/Victoria, and 22.7 (14.7, 35.0) for B/Yamagata. This study showed that IIV4-HD (60 µg HA/strain) provides improved immunogenicity without affecting vaccine safety in children.     

中国2002～2003年度流行性感冒监测分析

目的 阐明2002年4月至2003年6月国内流行性感冒(流感)流行特点和流感病毒优势株的特性。方法 流感病毒分离采用鸡胚和细胞分离；流感病毒亚型鉴定采用血球凝集抑制试验；对流行株的HA基因核酸测序，分析其亲缘关系和抗原变异性。结果 2002年4月至2003年6月，全国23个省(市)和自治区共采集流感样患者咽拭子标本共计16135份，经鉴定流感病毒阳性1113株，分离率6．9％。在1113株流感病毒中，A1型66株、A3型544株、B型流感病毒Yamagada98株和Victoria405株，分别占总分离数的5．9％、48．9％、8．8％和36．4％。优势流行株为H3N2和B型Victoria株。A3型流感病毒除主要分离于2002年12月和2003年1月外，在非流行高峰期也有一定数量的分离。而B型Victoria系流感病毒主要集中分离于冬季流行高峰期，其流行株核酸序列分析属B型Victoria系株。A3型毒株血凝素基因的HA1系统树分析表明，其与A／Panama／2007／99同源，且有某些变异存在。结论 虽然感染人群的流感毒株依然是A1、A3和B型交叉出现，但以A型(H3N2)和B型Victoria为优势株。与历年不同，B型Victoria分离比例增加及分布广泛是2002～2003年度的特点。A型(H3N2)流行株有变异迹象值得密切注意。     

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.     

Influenza B virus infections in Western Saxony,Germany in three consecutive seasons between 2015 and 2018: Analysis of molecular and clinical features

BackgroundThe impact of annual influenza epidemics and prevailing strains varies worldwide and regional. The majority of vaccines used contained two influenza A strains and only one influenza B strain (trivalent vaccine).AimThe aim of the study was to compare laboratory confirmed influenza B cases during three consecutive years with respect to vaccination history, clinical symptoms and molecular virology.MethodsPartial HA gene sequences were analyzed for lineage determination and complete HA sequence in cases with reported vaccination and in fatal cases. Clinical data were retrieved from patient charts.FindingsDuring the 2015/16 season, 75 influenza B cases were retrieved; 11 in 2016/17, and 274 in 2017/18. The frequency of Yamagata-lineage strains increased from 7.6% to 100%. No difference was detected in the relative frequency of co-morbidities in season 2017/18. 37.7% of the adult patients and 4.5% of pediatric patients were vaccinated against influenza.InterpretationPhylogenetically, Yamagata strains clustered similarly in 2017/2018 when compared to the previous two influenza seasons. While the relative frequency of influenza B cases differed, the clinical symptoms remained similar.ConclusionWorld Health Organization recommendations for the use of tetravalent vaccines that contain two influenza B strains (Yamagata and Victoria) in addition to the two influenza A strains (H1N1 and H3N2) should be implemented in national vaccination guidelines.FundingThis research was partially supported by the Association of Sponsors and Friends of Leipzig University.     

18岁以上人群接种四价流感病毒灭活疫苗免疫原性和安全性的Meta分析

目的 评价18岁以上人群接种四价流感病毒灭活疫苗(QIV)免疫原性和安全性.方法 检索美国国家医学图书馆数据库、Cochrane协作网图书馆、中国生物医学文献数据库、中国期刊全文数据库和万方全文数据库,将有关比较18岁以上人群接种QIV和三价流感病毒灭活疫苗(TIV)免疫原性和安全性的随机对照试验纳入分析.以接种疫苗21 d后产生的针对H1N1、H3N2、B/Victoria、B/Yamagata四个疫苗株的抗体保护率(SPR)和抗体阳转率(SCR)以及不良反应发生率作为结局指标,合并组间的SPR、SCR和不良反应发生率的相对危险度(RR).结果 共纳入5篇文献.针对B/Yamagata的SPR的RR是1.12(95％ CI:1.02～1.22),SCR的RR是2.11(95％ CI:1.51～2.95).针对B/Victoria的SPR的RR是1.14(95％ CI:1.03～1.25),SCR的RR是1.78(95％ CI:1.24～2.55).接种QIV和TIV(含B/Yamagata)后接种部位疼痛发生率的RR是1.23 (95％ CI:1.05～1.44).结论 18岁以上成人接种QIV不仅可以产生与TIV相似的免疫效果和安全性,而且可以对TIV未包含的乙型流感疫苗株产生较好免疫效果.     

Evaluation of the safety, reactogenicity and immunogenicity of FluBlok® trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy adults 50-64 years of age

Background

Alternative methods for influenza vaccine production are needed to ensure adequate supplies.

Methods

Healthy adults 50-64 years were assigned randomly to receive one intramuscular injection of trivalent recombinant hemagglutinin (rHA) or U.S. licensed trivalent inactivated vaccine (TIV) containing H1, H3 and B antigens (Ag) derived from 2007 to 2008 influenza virus strains A/Solomon Islands/03/2006 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004. Each rHA dose contained 45 μg HA/strain of the 2007-2008 FDA-recommended Ag vs. 15 μg/strain for TIV. Antibody (Ab) responses were measured using a hemagglutination-inhibition (HAI) assay at baseline and 28 days post-vaccination. Respiratory samples for viral culture were collected from subjects with influenza-like illness (ILI) during the 2007-2008 season in the U.S.

Results

601 subjects were enrolled. Vaccines were well tolerated. Seroconversion (the percentage of subjects with either (a) a pre-vaccination HAI titer ≤10 and a post-vaccination HAI titer ≥40 or (b) a pre-vaccination titer ≥10 and a minimum four-fold rise in post-vaccination HAI antibody titer) in the TIV and rHA groups, respectively, was obtained in 66% vs. 72% for H1; 44% vs. 61% for H3; and 41% vs. 41% for B. Proportions achieving titers ≥40 were 96% vs. 96% for H1, 75% vs. 85% for H3, and 94% vs. 93% vs. B. Geometric mean titer ratios at day 28 (TIV/rHA) were 0.77 for H1; 0.58 for H3; and 1.05 for B, respectively. ILI frequencies were low and similar in both groups.

Conclusions

Both vaccines were safe and immunogenic. Ab responses vs. H1 and H3 Ags were significantly higher in the rHA group, with similar responses to B. Furthermore, the FluBlok group had a statistically significantly higher seroconversion rate against influenza A/H3N2 compared to the TIV group.     

流感病毒在MDCK细胞上培养条件的优化分析

摘要:目的　优化甲、乙型流感病毒在MDCK细胞上的培养条件,提高流感病毒的分离效果。方法　将5种流感病毒液（甲型流感病毒:甲型H1N1、季节性H1N1、季节性H3N2和乙型流感病毒:Victoria、Yamagata）分别接种于MDCK细胞,通过比较不同的病毒接种量（30 μl/cm2、60 μl/cm2、90 μl/cm2、120 μl/cm2、150 μl/cm2）、不同的病毒孵育时间（0.5 h、1.0 h、1.5 h、2.0 h、2.5 h、3.0 h）、不同的TPCK-胰酶添加浓度（1.0 μg/ml、2.0 μg/ml、3.0 μg/ml、4.0 μg/ml、5/0 μg/ml）以及不同的MDCK细胞增毒代次（连续盲传5代）对5种流感病毒易感性的影响,确定其最佳分离效果;对分离后的病毒以红细胞凝集（HA）方法检测病毒滴度,结果　通过对比病毒HA滴度结果,5种流感病毒（甲型H1N1、季节性H1N1、季节性H3N2、Victoria和Yamagata）的最佳病毒接种量分别为:90 μl/cm2、90 μl/cm2、60 μl/cm2、120 μl/cm2、120 μl/cm2;最佳病毒孵育时间:甲型流感病毒为1.0～1.5 h,乙型流感病毒为2.0～2.5 h;胰酶最佳使用浓度分别是:2.0 μg/ml、2.0 μg/ml、2.0 μg/ml、3.0 μg/ml、3.0 μg/ml;最适宜的细胞增毒传代次数为:1代、3代、2代、2代、2代;甲型流感病毒经培养后病毒的HA滴度低于乙型流感,甲型H1N1流感病毒经培养后HA滴度较低。结论　甲型流感病毒对MDCK细胞的易感性低于乙型流感病毒;甲型H1N1流感病毒的分离效果低于季节性H1N1和季节性H3N2;Victoria与Yamagata的分离条件基本相同。     

Single-replication BM2SR vaccine provides sterilizing immunity and cross-lineage influenza B virus protection in mice

Both influenza A and B viruses cause outbreaks of seasonal influenza resulting in significant morbidity and mortality. There are two antigenically distinct lineages of influenza B virus, Yamagata lineage (YL) and Victoria lineage (VL). Since both B lineages have been co-circulating for years, more than 70% of influenza vaccines currently manufactured are quadrivalent consisting of influenza A (H1N1), influenza A (H3N2), influenza B (YL) and influenza B (VL) antigens. Although quadrivalent influenza vaccines tend to elevate immunity to both influenza B lineages, estimated overall vaccine efficacy against influenza B is still only around 42%. Thus, a more effective influenza B vaccine is needed.To meet this need, we generated BM2-deficient, single-replication (BM2SR) influenza B vaccine viruses that encode surface antigens from influenza B/Wisconsin/01/2010 (B/WI01, YL) and B/Brisbane/60/2008 (B/Bris60, VL) viruses. The BM2SR-WI01 and BM2SR-Bris60 vaccine viruses are replication-deficient in vitro and in vivo, and can only replicate in a cell line that expresses the complementing BM2 protein. Both BM2SR viruses were non-pathogenic to mice, and vaccinated animals showed elevated mucosal and serum antibody responses to both Yamagata and Victoria lineages in addition to cellular responses. Serum antibody responses included lineage-specific hemagglutinin inhibition antibody (HAI) responses as well as responses to the stem region of the hemagglutinin (HA). BM2SR vaccine viruses provided apparent sterilizing immunity to mice against intra- and inter-lineage drifted B virus challenge. The data presented here support the feasibility of BM2SR as a platform for next-generation trivalent influenza vaccine development.     

Public health impact of including two lineages of influenza B in a quadrivalent seasonal influenza vaccine

The annual trivalent influenza vaccine (TIV) includes viruses representing three influenza strains - one A/H1N1, one A/H3N2, and one B, although two antigenically distinct lineages of influenza B (Victoria and Yamagata) co-circulate annually in the United States. Predicting which lineage of influenza B will predominate during a season is challenging, and cross-protection by immunization against the other lineage is expected to be low. One proposed alternative is to produce a quadrivalent influenza vaccine (QIV) including an influenza B virus from each of the two circulating lineages. We estimated the additional public health benefit of QIV compared with TIV by calculating the expected impact on influenza-related health outcomes (illness, hospitalization, and death) over ten influenza seasons (1999/2000-2008/2009). We included data on the annual incidence of influenza-associated outcomes, virologic circulation, vaccine coverage, and vaccine effectiveness. We also considered annual vaccine production capacity, since available resources would have produced four vaccine viruses instead of three, potentially resulting in fewer doses of QIV. Use of QIV could have reduced annual cases (range: 2200-970,000), hospitalizations (range: 14-8200), and deaths (range: 1-485) in the US. During earlier seasons, adjusting production capacity for a fourth virus in QIV could have resulted in reduced overall influenza vaccine availability and net increases in influenza-associated outcomes. However, in recent seasons, the expected supply of QIV is likely to exceed the doses of vaccine actually administered. The potential net impact of QIV on influenza-associated outcomes is expected to vary between seasons, depending on annual variability in the incidence of influenza caused by the two influenza B lineages, vaccine coverage, and effectiveness. The additional protection provided by including a second lineage of influenza B could result in a modest reduction in influenza-associated outcomes.     

Cross-reactive antibodies in middle-aged and elderly volunteers after MF59-adjuvanted subunit trivalent influenza vaccine against B viruses of the B/Victoria or B/Yamagata lineages

This study evaluated whether MF59-adjuvanted subunit trivalent influenza vaccine for the 2003/04 winter season (A/Moscow/10/99, H3N2; A/New Caledonia/20/99, H1N1; B/Hong Kong/330/01) would confer protection against mismatched and frequently co-circulating variants of influenza B/Victoria- and B/Yamagata-like virus strains. Haemagglutination inhibiting (HI) antibodies were measured in middle-aged and elderly volunteers against the homologous B/Victoria-like vaccine strain (B/Hong Kong/330/01) and against mismatched B/Victoria-like (B/Malaysia/2506/04) and B/Yamagata-like (B/Singapore/379/99 and B/Shanghai/361/02) strains. Immunization induced significant increases in the amounts of HI antibodies against all influenza B strains under investigation. However, the responses against the heterologous B/Shanghai/361/02 virus did not reach the desirable values of seroprotection. An age-dependent decline of the responses was found for B/Victoria-like antigens, but not for B/Yamagata-like strains. Although further studies are needed, our data support the recommendation of including influenza B viruses of the B/Victoria and B/Yamagata lineages in the future influenza vaccine preparations.     

Immunogenicity and safety of Quadrivalent Influenza HA vaccine in Indonesian children: An open-labeled,bridging, clinical study

BackgroundInfluenza B (Yamagata/Victoria lineage) can cause severe forms of respiratory infection among the pediatric population as well as influenza A strains (H3N2/H1N1). Vaccination against all four strains is required to prevent infection and severe outcome. This study is the first study to assess the immunogenicity of Quadrivalent Influenza HA vaccine (QIV) and ascertain safety among children in Indonesia.MethodsThis is an open labeled, single arm, bridging clinical study involving unprimed healthy children 6–35 months of age (Group I) and 3–8 years of age (Group II). Subjects on both groups receiving two doses of QIV with a 28 days interval. Serology tests were performed on baseline and 28 days post-vaccination. Hemagglutination inhibition antibody titers were analyzed for Geometric Mean Titer (GMT), seroprotection, and seroconversion rates. Solicited reactions, unsolicited adverse events, and serious adverse events were observed up to 28 days post-vaccination.ResultsOut of 270 subjects enrolled, 269 subjects completed the study. Immunogenicity analysis were evaluated on 254 subjects. Seroprotection rates were ≥85% for all vaccine strains in both groups. Seroconversion of more than 4 folds for all strains occurred in both groups post-vaccination. In Group I, the increase of GMT for A/H1N1, A/H3N2, B/Texas, and B/Phuket was 12.5, 14.5, 8.2, and 6.4 folds, respectively. In Group II the increase of GMT for A/H1N1, A/H3N2, B/Texas, and B/Phuket was 14, 17, 10, and 8 folds, respectively. The majority of local adverse events (AEs) after the first and second immunizations were immediate injection-site pain (10.4% and 12.6%). The majority of systemic AEs after the first and second immunizations were delayed unsolicited AEs (14.8% and 14.9%). No vaccine-related serious adverse events or deaths were reported.ConclusionThe investigational QIV was immunogenic with an acceptable safety profile in children 6 months to 8 years of age.Clinical Trial registration: NCT03336593.