Serologic response after vaccination against influenza (A/H1N1)pdm09 in children with renal disease receiving oral immunosuppressive drugs

A limited number of reports are available regarding the effect of the influenza vaccine in pediatric patients receiving steroid and immunosuppressant therapy. The influenza A(H1N1)pdm09 vaccine was administered to 15 children with renal disease who were receiving steroid and immunosuppressant therapy (treatment group) and 23 children with who were not receiving these drugs (non-treatment group). Titer transition of the hemagglutination inhibition antibody was compared between the 2 groups immediately before vaccination and 4 weeks and 6 months after vaccination. Multivariate analysis showed a significant correlation between geometric mean titer, SCR, and SPR with age, while no correlation was observed between treatment with immunosuppressant therapy and efficacy. No serious adverse reactions occurred after vaccination.This strain is not present in existing influenza vaccines, and A(H1N1)pdm09HA vaccination was administered alone in 2009. The children in this study had not previously been exposed to this strain. Therefore, we evaluated the effect of the A(H1N1)pdm09HA vaccine without the effects of vaccination or past infection with A(H1N1)pdm09HA or A(H3N2) vaccination in the previous year.     

Host immune response to A(H1N1)pdm09 vaccination and infection: a one-year prospective study on six cohorts of subjects

Background

The long-term immunogenicity after novel vaccine against A(H1N1)pdm09 administration or natural infection has not been well investigated.

Methods

Six cohorts of subjects were followed up for over one year: one-dose A(H1N1)pdm09 vaccine recipient, A(H1N1)pdm09-seasonal trivalent vaccine recipients in different orders, confirmed A(H1N1)pdm09 patients without vaccination, with previous A(H1N1)pdm09 or seasonal influenza vaccination. Peripheral blood mononuclear cells and sera samples were collected at baseline and month 1, 2, 3, 7 and 14 after vaccination (infection). The immunogenicity was determined by hemagglutination-inhibition (HI) and B cell enzyme-linked immunospot (ELISPOT) assays.

Results

Single dose of A(H1N1)pdm09 vaccine elicited antibody titer of greater than 1:40 in 40% adults for 1 year and mean live of this adequate antibody was determined as 8.35 months. In contrast, responses after natural infections had lower peaking level and a relatively longer antibody duration, with estimated mean lives of 11.8 months. Pre-vaccination with the seasonal flu vaccine led to a significant reduction in HI titer to A(H1N1)pdm09 one month after vaccination, while pre-vaccination with A(H1N1)pdm09 had no effect on seasonal influenza vaccination. Seasonal flu vaccination followed by A(H1N1)pdm09 infection elicited boosting effect on antibody response against A(H1N1)pdm09. A similar memory B cell response was elicited from both vaccination and infection by ELISPOT assay.

Conclusions

The long-term decay of immunity for A(H1N1)pdm09 vaccine and natural infection indicates the need of revaccination after the host lose protection acquired from either vaccination or infection. Prior infection, rather than the pre-vaccination with seasonal influenza could act on the host immunity to elicit boosting effect on the A(H1N1)pdm09.     

Impact of prior infection and repeated vaccination on post-vaccination antibody titers of the influenza A(H1N1)pdm09 strain in Taiwan schoolchildren: Implications for public health

BackgroundThe objective of this study was to evaluate the effects of prior-infection and repeated vaccination on post-vaccination antibody titers.MethodsA(H1N1)pdm09 strain was included in 2009 pandemic monovalent, 2010–2011, and 2011–2012 trivalent influenza vaccines (MIVpdm09, TIV10/11, TIV11/12) in Taiwan. During the 2011–2012 influenza season, we conducted a prospective sero-epidemiological cohort study among schoolchildren from grades 1 – 6 in the two elementary schools in Taipei with documented A(H1N1)pdm09 vaccination records since 2009. Serum samples were collected at pre-vaccination, 1-month, and 4-months post-vaccination (T1, T2, T3). Anti-A(H1N1)pdm09 hemagglutination inhibition titers (HI-Ab-titers) were examined. We also investigated the impact of four vaccination histories [(1) no previous vaccination (None), (2) vaccinated in 2009–2010 season (09v), (3) vaccinated in 2010–2011 season (10v), and (4) vaccinated consecutively in 2009–2010 and 2010–2011 seasons (09v + 10v)] and pre-vaccination HI-Ab levels on post-vaccination HI-Ab responses as well as adjusted vaccine effectiveness (aVE) against serologically-defined infection from T2 to T3.ResultsTIV11/12 had zero serious adverse events reported. A(H1N1)pdm09 strain in TIV11/12 elicited seroprotective Ab-titers in 98% of children and showed promising protection (aVE: 70.3% [95% confidence interval (CI): 51.0–82.1%]). Previously unvaccinated but infected children had a 3.96 times higher T2 geometric mean titer (T2-GMT) of HI-Ab than those naïve to A(H1N1)pdm09 (GMT [95% CI]: 1039.7[585.3–1845.9] vs. 262.5[65.9–1045], p = 0.046). Previously vaccinated children with seroprotective T1-Ab-titers had a higher T2-GMT and a greater aVE than those with non-seroprotective T1-Ab-titers. Repeatedly vaccinated children had lower T2-GMT than those receiving primary doses of TIV11/12. However, after controlling prior infection and T1-Ab-titers, differences in T2-GMT among the four vaccination histories became insignificant (p = 0.16).ConclusionThis study supports the implementation of annual mass-vaccination with A(H1N1)pdm09 in schoolchildren for three consecutive influenza seasons when vaccine and circulating strains were well matched, and found that prior infection and pre-vaccination HI-Ab levels positively impacted post-vaccination HI-Ab responses.     

Impacts on influenza A(H1N1)pdm09 infection from cross-protection of seasonal trivalent influenza vaccines and A(H1N1)pdm09 vaccines: systematic review and meta-analyses

Cross-protection by seasonal trivalent influenza vaccines (TIVs) against pandemic influenza A H1N1 2009 (now known as A[H1N1]pdm09) infection is controversial; and the vaccine effectiveness (VE) of A(H1N1)pdm09 vaccines has important health-policy implications. Systematic reviews and meta-analyses are needed to assess the impacts of both seasonal TIVs and A(H1N1)pdm09 vaccines against A(H1N1)pdm09.We did a systematic literature search to identify observational and/or interventional studies reporting cross-protection of TIV and A(H1N1)pdm09 VE from when the pandemic started (2009) until July 2011. The studies fulfilling inclusion criteria were meta-analysed. For cross-protection and VE, respectively, we stratified by vaccine type, study design and endpoint. Seventeen studies (104,781 subjects) and 10 studies (2,906,860 subjects), respectively, reported cross-protection of seasonal TIV and VE of A(H1N1)pdm09 vaccines; six studies (17,229 subjects) reported on both. Thirteen studies (95,903 subjects) of cross-protection, eight studies (859,461 subjects) of VE, and five studies (9,643 subjects) of both were meta-analysed and revealed: (1) cross-protection for confirmed illness was 19% (95% confident interval=13-42%) based on 13 case-control studies with notable heterogeneity. A higher cross-protection of 34% (9-52%) was found in sensitivity analysis (excluding five studies with moderate/high risk of bias). Further exclusion of studies that recruited early in the pandemic (when non-recipients of TIV were more likely to have had non-pandemic influenza infection that may have been cross-protective) dramatically reduced heterogeneity. One RCT reported cross-protection of 38% (19-53%) for confirmed illness. One case-control study reported cross-protection of 50% (40-59%) against hospitalisation. (2) VE of A(H1N1)pdm09 for confirmed illness was 86% (73-93%) based on 11 case-control studies and 79% (22-94%) based on two cohort studies; VE against medically-attended ILI was 32% (8-50%) in one cohort study. TIVs provided moderate cross-protection against both laboratory-confirmed A(H1N1)pdm09 illness (based on eight case-control studies with low risk of bias and one RCT) and also hospitalisation. A finding of increased risk from seasonal vaccine was limited to cases recruited early in the pandemic. A(H1N1)pdm09 vaccines were highly effective against confirmed A(H1N1)pdm09 illness. Although cross-protection was less than the direct effect of strain-specific vaccination against A(H1N1)pdm09, TIV was generally beneficial before A(H1N1)pdm09 vaccine was available.     

No association between 2008-09 influenza vaccine and influenza A(H1N1)pdm09 virus infection, Manitoba, Canada, 2009

We conducted a population-based study in Manitoba, Canada, to investigate whether use of inactivated trivalent influenza vaccine (TIV) during the 2008-09 influenza season was associated with subsequent infection with influenza A(H1N1)pdm09 virus during the first wave of the 2009 pandemic. Data were obtained from a provincewide population-based immunization registry and laboratory-based influenza surveillance system. The test-negative case-control study included 831 case-patients with confirmed influenza A(H1N1)pdm09 virus infection and 2,479 controls, participants with test results negative for influenza A and B viruses. For the association of TIV receipt with influenza A(H1N1)pdm09 virus infection, the fully adjusted odds ratio was 1.0 (95% CI 0.7-1.4). Among case-patients, receipt of 2008-09 TIV was associated with a statistically nonsignificant 49% reduction in risk for hospitalization. In agreement with study findings outside Canada, our study in Manitoba indicates that the 2008-09 TIV neither increased nor decreased the risk for infection with influenza A(H1N1)pdm09 virus.     

Responses to live attenuated influenza vaccine in children vaccinated previously with Pandemrix (ASO3B adjuvanted pandemic A/H1N1pdm09)

BackgroundWe report a phase III/IV open-label study on the immunogenicity of a single dose of a Live Attenuated Influenza Vaccine (LAIV) (Fluenz™) in children naïve to, or in previous receipt of, AS03_B adjuvanted A/H1N1pdm09 influenza vaccine (Pandemrix™), to investigate whether early exposure to an adjuvanted subunit influenza vaccine impacts on subsequent response to quadrivalent LAIV (qLAIV).Method and findingsEligible children were enrolled to receive qLAIV and stratified according to previous Pandemrix™ vaccination. Functional antibody for the vaccine strains were analysed using Haemagglutination Inhibition (HAI); in addition antibodies to the A/H1N1pdm09 strain were measured by Neuraminidase Antibody Inhibition (NAI) and neutralisation assays. Fourfold titre increases by HAI were observed for 39% (95% confidence interval 33–46%) and 43% (37–51%) of subjects for the two influenza B vaccine strains and 8% (5–13%) for the A/H3N2 strain with no significant differences between the Pandemrix™ naïve or previously vaccinated groups in antibody tites pre- or post-vaccination or seroconversion rates. In both groups, the response to the qLAIV A/H1N1pdm09 component was barely detectable, overall HAI seroconversion rate 1.8% (0.5–4.7%). Previous receipt of Pandemrix™ was associated with significantly higher levels of A/H1N1pdm09 neutralising antibody, but decreased NAI titres pre-vaccination, with the differences maintained post-vaccination.ConclusionPrevious receipt of Pandemrix™ has had a significant impact on the influenza immune status of children several years later. Higher levels of neutralising antibody to A/H1N1pdm09 pre- and post-vaccination, but significantly lower levels of antibody to NA, were observed compared with Pandemrix™-naïve children, while responses to influenza B and A/H3N2 and antibody levels prior to vaccination were similar in both groups. This suggests that early vaccination with a powerful adjuvant maintains functional immunity for several years, which prevents natural infection. Alternatively, the AS03_B adjuvant may have re-directed the immune response, with focus towards viral HA and away from viral NA.     

Pandemic influenza A(H1N1)pdm09 improves vaccination routine in subsequent years: A cohort study from 2009 to 2011

Background

In 2009 the pandemic influenza virus A(H1N1)pdm09 emerged with guidance that people at risk should be vaccinated. It is unclear how this event affected the underlying seasonal vaccination rate in subsequent years.

Purpose

To investigate the association of pandemic influenza A(H1N1)pdm09 and seasonal flu vaccination status in 2009 with vaccination rates in 2010 and 2011.

Methods

Data were collected in 40 Dutch family practices on patients at risk for influenza during 2009–2011; data analysis was conducted in 2012.

Results

A multilevel logistic regression model (n = 41,843 patients) adjusted for practice and patient characteristics (age and gender, as well as those patient groups at risk), showed that people who were vaccinated against A(H1N1)pdm09 in 2009 were more likely to have been vaccinated in 2010 (OR 6.02; 95%CI 5.62–6.45, p < .0001). This likelihood was even more for people who were vaccinated against seasonal flu in 2009 (OR 13.83; 95%CI 12.93–14.78, p < .0001). A second analysis on the uptake rate in 2011 (n = 39,468 patients) showed that the influence of the vaccination state in 2009 declined after two years, but the diminishing effect was smaller for people vaccinated against A(H1N1)pdm09 than for seasonal flu (OR 5.50; 95%CI 5.13–5.90, p < .0001; OR 10.98; 95%CI 10.26–11.75, p < .0001, respectively).

Conclusion

Being vaccinated against A(H1N1)pdm09 and seasonal influenza in the pandemic year 2009 enhanced the probability of vaccination in the next year and this was still effective in 2011. This suggests that peoples’ vaccination routines were not changed by the rumor around the outbreak of A(H1N1)pdm09, but rather confirmed underlying behavior.     

Long term effectiveness of adjuvanted influenza A(H1N1)pdm09 vaccine in children

BackgroundImmunological studies have indicated that the effectiveness of AS03 adjuvanted monovalent influenza A(H1N1)pdm09 vaccine (Pandemrix^®) may be of longer duration than what is seen for non-adjuvanted seasonal influenza vaccines. Sixty-nine percent of children 6 months–18 years of age in Stockholm County received at least one dose of Pandemrix^® during the 2009 pandemic. We studied the effectiveness of the vaccine during the influenza seasons 2010–2011 and 2012–2013 in children hospitalized with virologically confirmed influenza. The season 2011–2012 was not included, since influenza A(H3N2) was the predominant circulating strain.MethodsIn a retrospective case-control study using a modified test-negative design we compared the percentage vaccinated with Pandemrix^® among children diagnosed with influenza A(H1N1)pdm09 (cases), with that of those diagnosed with influenza A(H3N2) or influenza B (controls) during the two seasons. We excluded children born after July 1, 2009, since only children who were 6 months of age or older received the pandemic vaccine in October–December 2009.ResultsDuring the 2010–2011 season, 3/16 (19%) of children diagnosed with influenza A(H1N1)pdm09, vs. 32/41 (78%) of those with influenza A(H3N2) or influenza B had been vaccinated with Pandemrix^® in 2009. The odds ratio, after adjustment for sex, age and underlying diseases, for becoming a case when vaccinated with Pandemrix^® was 0.083 (95%CI 0.014, 0.36), corresponding to a VE of 91.7%. During the season 2012–2013, there was no difference between the two groups; 59% of children diagnosed with influenza A(H3N2)/B and 60% of those with influenza A(H1N1)pdm09 had been vaccinated with Pandemrix^® in 2009.ConclusionThe AS03 adjuvanted monovalent influenza A(H1N1) pdm09 vaccine (Pandemrix^®) was effective in preventing hospital admission for influenza A(H1N1)pdm09 in children during at least two seasons.     

Key points in evaluating immunogenicity of pandemic influenza vaccines: A lesson from immunogenicity studies of influenza A(H1N1)pdm09 vaccine

IntroductionImmunogenicity studies on pandemic influenza vaccine are necessary to inform rapid development and implementation of a vaccine during a pandemic. Thus, strategies for immunogenicity assessment are required.ObjectiveTo identify essential factors to consider when evaluating the immunogenicity of pandemic influenza vaccines using the experience in Japan with the influenza A(H1N1)pdm09 vaccine.MethodsWe conducted a search of observational studies using PubMed and IchushiWeb. Search terms included “influenza vaccine AND (immunogenicity OR immune response) AND Japan AND (2009 OR pdm09) NOT review,” and was limited to studies conducted in humans.ResultsA total of 33 articles were identified, of which 16 articles met the inclusion criteria. Immunogenicity of the commercially available influenza A(H1N1)pdm09 vaccine satisfied the international criteria for influenza vaccine immunogenicity in all study populations. The most remarkable immune response was observed in junior high school students, while the lowest immune response was observed in hematological malignancy patients. Similar to immunogenicity studies on seasonal influenza vaccines, factors such as patient background (e.g., age, underlying condition, pre-vaccination titer, body mass index, etc.) and study procedure (e.g., concurrent measurement of pre- and post-vaccination antibody titer, effects of infection during the study period) may have affected the assessment of immunogenicity to the influenza A(H1N1)pdm09 vaccine. In addition, prior vaccination with the seasonal influenza vaccine may inhibit antibody induction by the influenza A(H1N1)pdm09 vaccine.ConclusionsThis review discusses factors and strategies that must be considered and addressed during immunogenicity assessments of pandemic influenza vaccines, which may provide useful information for future influenza pandemics.     

HI responses induced by seasonal influenza vaccination are associated with clinical protection and with seroprotection against non-homologous strains

Vaccination against influenza induces homologous as well as cross-specific hemagglutination inhibiting (HI) responses. Induction of cross-specific HI responses may be essential when the influenza strain does not match the vaccine strain, or even to confer a basic immune response against a pandemic influenza virus. We carried out a clinical study to evaluate the immunological responses after seasonal vaccination in healthy adults 18-60 years of age, receiving the yearly voluntary vaccination during the influenza season 2006/2007. Vaccinees of different age groups were followed for laboratory confirmed influenza (LCI) and homologous HI responses as well as cross-specific HI responses against the seasonal H1N1 strain of 2008 and pandemic H1N1 virus of 2009 (H1N1pdm09) were determined. Homologous HI titers that are generally associated with protection (i.e. seroprotective HI titers ≥40) were found in more than 70% of vaccinees. In contrast, low HI titers before and after vaccination were significantly associated with seasonal LCI. Cross-specific HI titers ≥40 against drifted seasonal H1N1 were found in 69% of vaccinees. Cross-specific HI titers ≥40 against H1N1pdm09 were also significantly induced, especially in the youngest age group. More specifically, cross-specific HI titers ≥40 against H1N1pdm09 were inversely correlated with age. We did not find a correlation between the subtype of influenza which was circulating at the age of birth of the vaccinees and cross-specific HI response against H1N1pdm09. These data indicate that the HI titers before and after vaccination determine the vaccination efficacy. In addition, in healthy adults between 18 and 60 years of age, young adults appear to be best able to mount a cross-protective HI response against H1N1pdm09 or drifted seasonal influenza after seasonal vaccination.     

No association between influenza A(H1N1)pdm09 vaccination and narcolepsy in South Korea: An ecological study

Background

There is concern about a possible association between influenza A(H1N1)pdm09 vaccination and narcolepsy. In this study, we assessed the incidence and incidence rate of narcolepsy in the South Korean population before and after the implementation of an A(H1N1)pdm09 vaccination campaign to see if vaccination led to a change in the occurrence of narcolepsy.

Methods

We conducted an ecological study, comparing incident cases and incidence rates for newly diagnosed narcolepsy case-patients in South Korea, between July 2006 and June 2011. We used data from the Health Insurance Review Agency and Korea Centers for Disease Control and Prevention, which have limited information on case ascertainment. During vaccination campaign period, South Korea used non-adjuvanted and MF59-adjuvanted A(H1N1)pdm09 vaccines.

Results

Generally, incidence rate was highest in prepandemic period. No trend toward increase in the incidence of narcolepsy after pandemic period was found. Observation of incidence by season did not suggest any time pattern for occurrence of narcolepsy.

Conclusion

No increase in cases or incidence rate for narcolepsy during the A(H1N1)pdm09 vaccination campaign was found in South Korea. Our data do not support the use of MF59-adjuvanted or non-adjuvanted A(H1N1)pdm09 vaccine as a trigger for narcolepsy on a population level.     

重型甲型H1N1流感患者外周血免疫细胞变化及其临床意义

目的 通过动态观察重型甲型H1N1流感(重症及危重症)患者外周血淋巴细胞的数量变化,探讨患者的免疫病理机制及淋巴细胞亚群检测在甲型H1N1流感诊断中的临床意义.方法 采用流式细胞技术检测2009年10-12月在我院住院治疗的41例重症、危重症甲型H1N1流感患者和同期41例轻症患者的外周血T、B和NK细胞数量.结果 在发病初期,重症及危重症患者外周血总T细胞、CD8+T细胞、NK细胞较轻症甲型H1N1流感患者显著降低(P＜0.01),CD4+T细胞较轻症患者降低(P＜0.05);危重症患者总T细胞、CD4+T细胞、CD8+T细胞、NK细胞低于重症患者(P＜0.01).恢复期重症及危重症甲型H1N1流感患者总T细胞、CD8+T细胞低于轻症患者(P＜0.05),NK细胞低于轻症患者(P＜0.01),B细胞高于轻症患者(P＜0.05).结论 重症及危重症甲型H1N1流感患者存在明显的细胞免疫损伤.     

Antibody but not memory B-cell responses are tuned-down in vertically HIV-1 infected children and young individuals being vaccinated yearly against influenza

Yearly immunization against seasonal influenza is highly recommended for HIV-1 infected individuals but evaluating the success of vaccination by serological markers may not be fully informative in this population. Recently, it has been hypothesized that the generation of long-lasting immune responses may depend on whether similar antigens challenge the immune system frequently and intermittently. In the present study, in order to search for additional correlates of vaccine-induced protective immunity and to further dissect this theory, both humoral and memory B-cell responses to the trivalent 2012–2013 seasonal influenza vaccination has been evaluated by strain-specific (separately for H1N1, H3N2 and B strain) standard hemagglutination inhibition (HI) assay and B-cell enzyme-linked immunosorbent spot (ELISpot) in a cohort of vertically HIV-1 infected children and young individuals as compared to age-matched healthy controls. A high number of HIV-1 infected individuals had protective antibody levels prior to vaccination and showed low seroconversion rates after vaccination as compared to healthy controls. On the contrary, similar frequencies of influenza-specific memory B-cells were detected by B-cell ELISpot in both groups suggesting that an adequate B-cell response has been elicited. Data from the H1N1 strain, which is recurrent in seasonal influenza vaccines since 2009, pointed out decreasing antibody but not memory B-cell responses for HIV-1 infected patients being vaccinated for a greater number of years. Further investigations are required to standardize the influenza-specific B-cell ELISpot and to understand whether it could be used routinely as an additional tool to evaluate response to influenza vaccination in immune-compromised individuals being vaccinated yearly.     

A Historical Perspective of Influenza A(H1N2) Virus

The emergence and transition to pandemic status of the influenza A(H1N1)A(H1N1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. Within a short time of the initial emergence of A(H1N1)pdm09 virus, novel reassortants were isolated from swine. In late 2011, a variant (v) H3N2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase with limited person-to-person transmission. During 2012 in the United States, an A(H1N2)v virus was transmitted to humans from swine. During the same year, Australia recorded its first H1N2 subtype infection among swine. The A(H3N2)v and A(H1N2)v viruses contained the matrix protein from the A(H1N1)pdm09 virus, raising the possibility of increased transmissibility among humans and underscoring the potential for influenza pandemics of novel swine-origin viruses. We report on the differing histories of A(H1N2) viruses among humans and animals.     

Seasonal influenza vaccines induced high levels of neutralizing cross-reactive antibody responses against different genetic group influenza A(H1N1)pdm09 viruses

Influenza A(H1N1)pdm09 viruses have been circulating throughout the world since the 2009 pandemic. A/California/07/2009 (H1N1) virus was included in seasonal influenza vaccines for seven years altogether, providing a great opportunity to analyse vaccine-induced immunity in relation to the postpandemic evolution of the A(H1N1)pdm09 virus. Serum antibodies against various epidemic strains of influenza A(H1N1)pdm09 viruses were measured among health care workers (HCWs) by haemagglutination inhibition and microneutralization tests before and after 2010 and 2012 seasonal influenza vaccinations. We detected high responses of vaccine-induced neutralizing antibodies to six distinct genetic groups. Our results indicate antigenic similarity between vaccine and circulating A(H1N1)pdm09 strains, and substantial vaccine-induced immunity against circulating epidemic viruses.     

2018-2019年宁夏甲型H1N1流感病毒血凝素基因组序列分析

目的 了解宁夏2018-2019流感监测年度流感病毒病原学检测情况,分析甲型H1N1流感病毒血凝素（HA）基因特征。方法 采用real time RT-PCR方法对流感监测哨点医院采集的流感样病例（ILI）标本进行核酸检测;对阳性标本进行毒株分离;提取甲型H1N1毒株的RNA,采用RT-PCR方法扩增HA片段并测序,利用生物信息软件对测序结果进行比对分析。结果 宁夏流感网络实验室检测咽拭子标本共5214份,核酸检测阳性数为760份,其中甲型H1N1阳性数为485份,占总阳性数的63.82%,分离出甲型H1N1毒株 161株。宁夏分离毒株与疫苗株A/Califaoria/07/2009不在同一进化分支,同源性为92.6%~96.3%;与疫苗株A/Michigan/45/2015(H1N1)为同一进化分支,同源性为96.6%~98.1%。与疫苗株A/Califaoria/07/2009比较,抗原位点、受体结合位点及其他位点均有变异,除毒株 A/Ningxia_Xixia/SWL1176/2019(H1N1)第222位氨基酸发生D222G变异外,其他甲型H1N1流感毒株均未发生D222G变异。所有毒株增加糖基化位点162NQT,个别毒株糖基化位点增加2~3个。结论 宁夏2018 -2019年度流感优势毒株为甲型H1N1毒株。序列分析表明甲型H1N1病毒发生了不同程度的变异,在抗原特异性、毒力和感染性上有可能已经发生变化,需要及时更换疫苗株成分。     

Adaptation of influenza A(H1N1)pdm09 virus in experimental mouse models

In the present study, three mouse-adapted variants of influenza A(H1N1)pdm09 virus were obtained by lung-to-lung passages of BALB/c, C57BL/6z and CD1 mice. The significantly increased virulence and pathogenicity of all of the mouse-adapted variants induced 100% mortality in the adapted mice. Genetic analysis indicated that the increased virulence of all of the mouse-adapted variants reflected the incremental acquisition of several mutations in PB2, PB1, HA, NP, NA, and NS2 proteins. Identical amino acid substitutions were also detected in all of the mouse-adapted variants of A(H1N1)pdm09 virus, including PB2 (K251R), PB1 (V652A), NP (I353V), NA (I106V, N248D) and NS1 (G159E). Apparently, influenza A(H1N1)pdm09 virus easily adapted to the host after serial passages in the lungs, inducing 100% lethality in the last experimental group. However, cross-challenge revealed that not all adapted variants are pathogenic for different laboratory mice. Such important results should be considered when using the influenza mice model.     

Effectiveness of the current and prior influenza vaccinations in Northern Spain, 2018–2019

BackgroundThe population targeted for influenza vaccination can be repeatedly vaccinated over successive seasons, and vaccines received in previous seasons may retain preventive effect. This study aims to estimate the effectiveness of inactivated influenza vaccines received in the current and prior seasons in the 2018–2019 season.MethodsInfluenza-like illness patients attended by sentinel general practitioners or admitted to hospitals in Navarre, Spain, were tested for influenza. Vaccination status in the current and three prior seasons was obtained from the vaccination registry. The test-negative design was used to estimate the vaccine effectiveness.ResultsA total of 381 influenza A(H1N1)pdm09 cases, 341 A(H3N2) cases and 1222 controls were analysed. As compared to individuals unvaccinated in the current and three prior seasons, the influenza vaccine effectiveness against A(H1N1)pdm09 was 57% (95% confidence interval [CI]: 40%, 70%) for current season vaccination regardless of prior doses and 48% (95%CI: 14%, 68%) for vaccination in prior seasons but not in the current season. These estimates were 12% (95%CI: −23%, 37%) and 27% (95%CI: −22%, 56%), respectively, against influenza A(H3N2). Individuals vaccinated with the two A(H1N1)pdm09 strains in influenza vaccines since 2009, A/Michigan/45/2015 and A/California/07/2009, had higher protection (68%; 95%CI: 53%, 77%) than those vaccinated with A/Michigan/45/2015 only (29%, p = 0.020) or with A/California/07/2009 only (34%, p = 0.005).ConclusionThese results suggest moderate effectiveness of influenza vaccination against A(H1N1)pdm09 and low effectiveness against A(H3N2) influenza in the 2018–2019 season. Vaccination in prior seasons maintained a notable protective effect. Strains included in previous vaccines were as effective as the current vaccine strain, and both added their effects against influenza A(H1N1)pdm09.