What the public was saying about the H1N1 vaccine: perceptions and issues discussed in on-line comments during the 2009 H1N1 pandemic

During the 2009 H1N1 pandemic, a vaccine was made available to all Canadians. Despite efforts to promote vaccination, the public's intent to vaccinate remained low. In order to better understand the public's resistance to getting vaccinated, this study addressed factors that influenced the public's decision making about uptake. To do this, we used a relatively novel source of qualitative data--comments posted on-line in response to news articles on a particular topic. This study analysed 1,796 comments posted in response to 12 articles dealing with H1N1 vaccine on websites of three major Canadian news sources. Articles were selected based on topic and number of comments. A second objective was to assess the extent to which on-line comments can be used as a reliable data source to capture public attitudes during a health crisis. The following seven themes were mentioned in at least 5% of the comments (% indicates the percentage of comments that included the theme): fear of H1N1 (18.8%); responsibility of media (17.8%); government competency (17.7%); government trustworthiness (10.7%); fear of H1N1 vaccine (8.1%); pharmaceutical companies (7.6%); and personal protective measures (5.8%). It is assumed that the more frequently a theme was mentioned, the more that theme influenced decision making about vaccination. These key themes for the public were often not aligned with the issues and information officials perceived, and conveyed, as relevant in the decision making process. The main themes from the comments were consistent with results from surveys and focus groups addressing similar issues, which suggest that on-line comments do provide a reliable source of qualitative data on attitudes and perceptions of issues that emerge in a health crisis. The insights derived from the comments can contribute to improved communication and policy decisions about vaccination in health crises that incorporate the public's views.     

Attitudes toward and uptake of H1N1 vaccine among health care workers during the 2009 H1N1 pandemic

Background

Though recommended by many and mandated by some, influenza vaccination rates among health care workers, even in pandemics, remain below optimal levels. The objective of this study was to assess vaccination uptake, attitudes, and distinguishing characteristics (including doctor-nurse differences) of health care workers who did and did not receive the pandemic H1N1 influenza vaccine in late 2009.

Methodology/Principal Findings

In early 2010 we mailed a self-administered survey to 800 physicians and 800 nurses currently licensed and practicing in Minnesota. 1,073 individuals responded (cooperation rate: 69%). 85% and 62% of Minnesota physicians and nurses, respectively, reported being vaccinated. Accurately estimating the risk of vaccine side effects (OR 2.0; 95% CI 1.5–2.7), agreeing with a professional obligation to be vaccinated (OR 10.1; 95% CI 7.1–14.2), an ethical obligation to follow public health authorities'' recommendations (OR 9.9; 95% CI 6.6–14.9), and laws mandating pandemic vaccination (OR 3.1; 95% CI 2.3–4.1) were all independently associated with receiving the H1N1 influenza vaccine.

Conclusions/Significance

While a majority of health care workers in one midwestern state reported receiving the pandemic H1N1 vaccine, physicians and nurses differed significantly in vaccination uptake. Several key attitudes and perceptions may influence health care workers'' decisions regarding vaccination. These data inform how states might optimally enlist health care workers'' support in achieving vaccination goals during a pandemic.     

The responses of Aboriginal Canadians to adjuvanted pandemic (H1N1) 2009 influenza vaccine

Background:

Because many Aboriginal Canadians had severe cases of pandemic (H1N1) 2009 influenza, they were given priority access to vaccine. However, it was not known if the single recommended dose would adequately protect people at high risk, prompting our study to assess responses to the vaccine among Aboriginal Canadians.

Methods:

We enrolled First Nations and Métis adults aged 20–59 years in our prospective cohort study. Participants were given one 0.5-mL dose of ASO3-adjuvanted pandemic (H1N1) 2009 vaccine (Arepanrix, GlaxoSmithKline Canada). Blood samples were taken at baseline and 21–28 days after vaccination. Paired sera were tested for hemagglutination-inhibiting antibodies at a reference laboratory. To assess vaccine safety, we monitored the injection site symptoms of each participant for seven days. We also monitored patients for general symptoms within 7 days of vaccination and any use of the health care system for 21–28 days after vaccination.

Results:

We enrolled 138 participants in the study (95 First Nations, 43 Métis), 137 of whom provided all safety data and 136 of whom provided both blood samples. First Nations and Métis participants had similar characteristics, including high rates of chronic health conditions (74.4%–76.8%). Pre-existing antibody to the virus was detected in 34.3% of the participants, all of whom boosted strongly with vaccination (seroprotection rate [titre ≥ 40] 100%, geometric mean titre 531–667). Particpants with no pre-existing antibody also responded well. Fifty-eight of 59 (98.3%) First Nations participants showed seroprotection and a geometric mean titre of 353.6; all 30 Métis participants with no pre-existing antibody showed seroprotection and a geometric mean titre of 376.2. Pain at the injection site and general symptoms frequently occurred but were short-lived and generally not severe, although three participants (2.2%) sought medical attention for general symptoms.

Interpretation:

First Nations and Métis adults responded robustly to ASO3-adjuvanted pandemic (H1N1) 2009 vaccine. Virtually all participants showed protective titres, including those with chronic health conditions.

Trial registration:

ClinicalTrials.gov trial register no. NCT.01001026.During the first wave of the H1N1 pandemic in Canada in 2009, some First Nations communities were severely affected, with younger adults and children most at risk for severe disease.^1,2 Whereas Aboriginal Canadians make up 3.4% of the population (with 1.14 million people), they accounted for 16% of admissions to hospital during the first wave of the pandemic, and 43% of Aboriginal patients had underlying medical conditions.³ The increased rate of severe disease might have resulted from residential crowding, prevalence of chronic health conditions, delayed access to health care or suboptimal immune responses to infection.⁴ When a federally funded, ASO3-adjuvanted (squalene/tocopherol) pandemic vaccine became available for Canadians later in 2009,⁵ Aboriginal people were given priority access to it.³ However, dosing requirements at the time were tentative. Previous studies of an ASO3-adjuvanted influenza A (H5N1) vaccine established that two doses were needed for immunity in adults.⁶ Because the 2009 influenza (H1N1) pandemic occurred without warning, no prepandemic studies had been done with vaccines based on this novel swine-derived virus.⁷The ASO3-adjuvanted pandemic (H1N1) 2009 vaccine manufactured in Canada (Arepanrix, GlaxoSmithKline, Laval, Quebec) was released for public use as soon as it was available, unstudied, to mitigate morbidity during the pandemic’s second wave, which was already in progress. A single 3.75-μg dose of hemagglutinin was recommended for adults using the preliminary results of a European trial of another ASO3-adjuvanted vaccine (Pandemrix, GlaxoSmithKline, Rixensart, Belgium) given to 65 adults aged 18–60 years.⁸ The European product was believed to be equivalent to the Canadian-made vaccine, but this had not yet been shown.We wondered if the recommended single dose would be adequate for Aboriginal Canadian adults given their heightened risk of severe influenza during the first wave. We were unable to identify any previous studies of influenza vaccines involving Aboriginal Canadians to determine if their responses would be similar to other Canadians or to the healthy European study participants on whom the dosing recommendation was based. Consequently, we undertook a study involving First Nations and Métis adults to assess their responses to the pandemic vaccine.     

Immunogenicity and efficacy of flagellin-fused vaccine candidates targeting 2009 pandemic H1N1 influenza in mice

We have previously demonstrated that the globular head of the hemagglutinin (HA) antigen fused to flagellin of Salmonella typhimurium fljB (STF2, a TLR5 ligand) elicits protective immunity to H1N1 and H5N1 lethal influenza infections in mice (Song et al., 2008, PLoS ONE 3, e2257; Song et al., 2009, Vaccine 27, 5875–5888). These fusion proteins can be efficiently and economically manufactured in E. coli fermentation systems as next generation pandemic and seasonal influenza vaccines. Here we report immunogenicity and efficacy results of three vaccine candidates in which the HA globular head of A/California/07/2009 (H1N1) was fused to STF2 at the C-terminus (STF2.HA1), in replace of domain 3 (STF2R3.HA1), or in both positions (STF2R3.2xHA1). For all three vaccines, two subcutaneous immunizations of BALB/c mice with doses of either 0.3 or 3 µg elicit robust neutralizing (HAI) antibodies, that lead to > = 2 Log₁₀ unit reduction in day 4 lung virus titer and full protection against a lethal A/California/04/2009 challenge. Vaccination with doses as low as 0.03 µg results in partial to full protection. Each candidate, particularly the STF2R3.HA1 and STF2R3.2xHA1 candidates, elicits robust neutralizing antibody responses that last for at least 8 months. The STF2R3.HA1 candidate, which was intermediately protective in the challenge models, is more immunogenic than the H1N1 components of two commercially available trivalent inactivated influenza vaccines (TIVs) in mice. Taken together, the results demonstrate that all three vaccine candidates are highly immunogenic and efficacious in mice, and that the STF2R3.2xHA1 format is the most effective candidate vaccine format.     

Transmission characteristics of the 2009 H1N1 influenza pandemic: comparison of 8 Southern hemisphere countries

While in Northern hemisphere countries, the pandemic H1N1 virus (H1N1pdm) was introduced outside of the typical influenza season, Southern hemisphere countries experienced a single wave of transmission during their 2009 winter season. This provides a unique opportunity to compare the spread of a single virus in different countries and study the factors influencing its transmission. Here, we estimate and compare transmission characteristics of H1N1pdm for eight Southern hemisphere countries/states: Argentina, Australia, Bolivia, Brazil, Chile, New Zealand, South Africa and Victoria (Australia). Weekly incidence of cases and age-distribution of cumulative cases were extracted from public reports of countries'' surveillance systems. Estimates of the reproduction numbers, R ₀, empirically derived from the country-epidemics'' early exponential phase, were positively associated with the proportion of children in the populations (p = 0.004). To explore the role of demography in explaining differences in transmission intensity, we then fitted a dynamic age-structured model of influenza transmission to available incidence data for each country independently, and for all the countries simultaneously. Posterior median estimates of R ₀ ranged 1.2–1.8 for the country-specific fits, and 1.29–1.47 for the global fits. Corresponding estimates for overall attack-rate were in the range 20–50%. All model fits indicated a significant decrease in susceptibility to infection with age. These results confirm the transmissibility of the 2009 H1N1 pandemic virus was relatively low compared with past pandemics. The pattern of age-dependent susceptibility found confirms that older populations had substantial – though partial - pre-existing immunity, presumably due to exposure to heterologous influenza strains. Our analysis indicates that between-country-differences in transmission were at least partly due to differences in population demography.     

Overview/reflections on the 2009 H1N1 pandemic

The Influenza A H1N1 2009 pandemic was a test of the global public health response. Strategies that worked included mass vaccine production and antivirals while quarantine and isolation proved futile. Among the lessons learned was the importance of severity in the definition of a pandemic.     

Comparative analysis of hemagglutinin of 2009 H1N1 influenza A pandemic indicates its evolution to 1918 H1N1 pandemic

To gain insight into the possible origin of the hemagglutinin of 2009 outbreak, we performed its comparative analysis with hemagglutinin of influenza viral strains from 2005 to 2008 and the past pandemics of 1977, 1968, 1957 and 1918. This insilico analysis showed a maximum sequence similarity between 2009 and 1918 pandemics. Primary structure analysis, antigenic and glycosylation site analyses revealed that this protein has evolved from 1918 pandemic. Phylogenetic analysis of HA amino acid sequence of 2009 influenza A(H1N1) viruses indicated that this virus possesses a distinctive evolutionary trait with 1918 influenza A virus. Although the disordered sequences are different among all the isolates, the disordered positions and sequences between 2009 and 1918 isolates show a greater similarity. Thus these analyses contribute to the evidence of the evolution of 2009 pandemic from 1918 influenza pandemic. This is the first computational evolutionary analysis of HA protein of 2009 H1N1 pandemic.     

Modelling mitigation strategies for pandemic (H1N1) 2009

Background

The 2009 influenza A (H1N1) pandemic has required decision-makers to act in the face of substantial uncertainties. Simulation models can be used to project the effectiveness of mitigation strategies, but the choice of the best scenario may change depending on model assumptions and uncertainties.

Methods

We developed a simulation model of a pandemic (H1N1) 2009 outbreak in a structured population using demographic data from a medium-sized city in Ontario and epidemiologic influenza pandemic data. We projected the attack rate under different combinations of vaccination, school closure and antiviral drug strategies (with corresponding “trigger” conditions). To assess the impact of epidemiologic and program uncertainty, we used “combinatorial uncertainty analysis.” This permitted us to identify the general features of public health response programs that resulted in the lowest attack rates.

Results

Delays in vaccination of 30 days or more reduced the effectiveness of vaccination in lowering the attack rate. However, pre-existing immunity in 15% or more of the population kept the attack rates low, even if the whole population was not vaccinated or vaccination was delayed. School closure was effective in reducing the attack rate, especially if applied early in the outbreak, but this is not necessary if vaccine is available early or if pre-existing immunity is strong.

Interpretation

Early action, especially rapid vaccine deployment, is disproportionately effective in reducing the attack rate. This finding is particularly important given the early appearance of pandemic (H1N1) 2009 in many schools in September 2009.Jurisdictions in the northern hemisphere are bracing for a “fall wave” of pandemic (H1N1) 2009.^1–3 Decision-makers face uncertainty, not just with respect to epidemiologic characteristics of the virus,⁴ but also program uncertainties related to feasibility, timeliness and effectiveness of mitigation strategies.⁵ Policy decisions must be made against this backdrop of uncertainty. However, the effectiveness of any mitigation strategy generally depends on the epidemiologic characteristics of the pathogen as well as the other mitigation strategies adopted. Mathematical models can project strategy effectiveness under hypothetical epidemiologic and program scenarios.^6–12 In the case of pandemic influenza, models have been used to assess the effectiveness of school closure⁷ and optimal use of antiviral drug^6,9,10 and vaccination strategies.⁸ However, model projections can be sensitive to input parameter values; thus, data uncertainty is an issue.¹³ Uncertainty analysis can help address the impact of uncertainties on model predictions but is often underutilized.¹³In this article, we present a simulation model of pandemic influenza transmission and mitigation in a population. This model projects the overall attack rate (percentage of people infected) during an outbreak. We introduce a formal method of uncertainty analysis that has not previously been applied to pandemic influenza, and we use this method to assess the impact of epidemiologic and program uncertainties. The model is intended to address the following policy questions that have been raised during the 2009 influenza pandemic: What is the impact of delayed vaccine delivery on attack rates? Can attack rates be substantially reduced without closing schools? What is the impact of pre-existing immunity from spring and summer 2009? We addressed these questions using a simulation model that projects the impact of vaccination, school closure and antiviral drug treatment strategies on attack rates.     

Seroprevalence of pandemic H1N1 antibody among health care workers in Hong Kong following receipt of monovalent 2009 H1N1 influenza vaccine

Background

Healthcare workers in many countries are recommended to receive influenza vaccine to protect themselves as well as patients. A monovalent H1N1 vaccine became available in Hong Kong in December 2009 and around 10% of local healthcare workers had received the vaccine by February 2010.

Methods

We conducted a cross-sectional study of the prevalence of antibody to pandemic (H1N1) 2009 among HCWs in Hong Kong in February–March 2010 following the first pandemic wave and the pH1N1 vaccination campaign. In this study we focus on the subset of healthcare workers who reported receipt of non-adjuvanted monovalent 2009 H1N1 vaccine (Panenza, Sanofi Pasteur). Sera collected from HCWs were tested for antibody against the pH1N1 virus by hemagglutination inhibition (HI) and viral neutralization (VN) assays.

Results

We enrolled 703 HCWs. Among 104 HCWs who reported receipt of pH1N1 vaccine, 54% (95% confidence interval (CI): 44%–63%) had antibody titer ≥1∶40 by HI and 42% (95% CI: 33%–52%) had antibody titer ≥1∶40 by VN. The proportion of HCWs with antibody titer ≥1∶40 by HI and VN significantly decreased with age, and the proportion with antibody titer ≥1∶40 by VN was marginally significantly lower among HCWs who reported prior receipt of 2007–08 seasonal influenza vaccine (odds ratio: 0.43; 95% CI: 0.19–1.00). After adjustment for age, the effect of prior seasonal vaccine receipt was not statistically significant.

Conclusions

Our findings suggest that monovalent H1N1 vaccine may have had suboptimal immunogenicity in HCWs in Hong Kong. Larger studies are required to confirm whether influenza vaccine maintains high efficacy and effectiveness in HCWs.     

Improved antigen yield in pandemic H1N1 (2009) candidate vaccine viruses with chimeric hemagglutinin molecules

The candidate pandemic H1N1 vaccine virus NIBRG-121 was derived by reverse genetics and comprises the hemagglutinin (HA) and neuraminidase (NA) genes from A/California/7/2009 (CAL) on an A/Puerto Rico/8/34 (PR8) backbone. NIBRG-121 was found to grow poorly in eggs, compared to seasonal H1N1 candidate vaccine viruses. Based on our previous study with H5N1 candidate vaccine viruses, we generated two new viruses with chimeric PR8/CAL HA genes. Here we show that these new viruses have considerably improved growth in eggs and are therefore better candidate vaccine viruses for use in production of pandemic H1N1 (2009) vaccine.     

The age-specific cumulative incidence of infection with pandemic influenza H1N1 2009 was similar in various countries prior to vaccination

Background

During the influenza pandemic of 2009 estimates of symptomatic and asymptomatic infection were needed to guide vaccination policies and inform other control measures. Serological studies are the most reliable way to measure influenza infection independent of symptoms. We reviewed all published serological studies that estimated the cumulative incidence of infection with pandemic influenza H1N1 2009 prior to the initiation of population-based vaccination against the pandemic strain.

Methodology and Principal Findings

We searched for studies that estimated the cumulative incidence of pandemic influenza infection in the wider community. We excluded studies that did not include both pre- and post-pandemic serological sampling and studies that included response to vaccination. We identified 47 potentially eligible studies and included 12 of them in the review. Where there had been a significant first wave, the cumulative incidence of pandemic influenza infection was reported in the range 16%–28% in pre-school aged children, 34%–43% in school aged children and 12%–15% in young adults. Only 2%–3% of older adults were infected. The proportion of the entire population infected ranged from 11%–18%. We re-estimated the cumulative incidence to account for the small proportion of infections that may not have been detected by serology, and performed direct age-standardisation to the study population. For those countries where it could be calculated, this suggested a population cumulative incidence in the range 11%–21%.

Conclusions and Significance

Around the world, the cumulative incidence of infection (which is higher than the cumulative incidence of clinical disease) was below that anticipated prior to the pandemic. Serological studies need to be routine in order to be sufficiently timely to provide support for decisions about vaccination.     

Estimating transmission probability in schools for the 2009 H1N1 influenza pandemic in Italy

Background

Epidemic models are being extensively used to understand the main pathways of spread of infectious diseases, and thus to assess control methods. Schools are well known to represent hot spots for epidemic spread; hence, understanding typical patterns of infection transmission within schools is crucial for designing adequate control strategies. The attention that was given to the 2009 A/H1N1pdm09 flu pandemic has made it possible to collect detailed data on the occurrence of influenza-like illness (ILI) symptoms in two primary schools of Trento, Italy.

Results

The data collected in the two schools were used to calibrate a discrete-time SIR model, which was designed to estimate the probabilities of influenza transmission within the classes, grades and schools using Markov Chain Monte Carlo (MCMC) methods. We found that the virus was mainly transmitted within class, with lower levels of transmission between students in the same grade and even lower, though not significantly so, among different grades within the schools. We estimated median values of R ₀ from the epidemic curves in the two schools of 1.16 and 1.40; on the other hand, we estimated the average number of students infected by the first school case to be 0.85 and 1.09 in the two schools.

Conclusions

The discrepancy between the values of R ₀ estimated from the epidemic curve or from the within-school transmission probabilities suggests that household and community transmission played an important role in sustaining the school epidemics. The high probability of infection between students in the same class confirms that targeting within-class transmission is key to controlling the spread of influenza in school settings and, as a consequence, in the general population.

     

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics.     

Prevalence of seroprotection against the pandemic (H1N1) virus after the 2009 pandemic

Background

Before pandemic (H1N1) 2009, less than 10% of serum samples collected from all age groups in the Lower Mainland of British Columbia, Canada, showed seroprotection against the pandemic (H1N1) 2009 virus, except those from very elderly people. We reassessed this profile of seroprotection by age in the same region six months after the fall 2009 pandemic and vaccination campaign.

Methods

We evaluated 100 anonymized serum samples per 10-year age group based on convenience sampling. We measured levels of antibody against the pandemic virus by hemagglutination inhibition and microneutralization assays. We assessed geometric mean titres and the proportion of people with seroprotective antibody levels (hemagglutination inhibition titre ≥ 40). We performed sensitivity analyses to evaluate titre thresholds of 80, 20 and 10.

Results

Serum samples from 1127 people aged 9 months to 101 years were obtained. The overall age-standardized proportion of people with seroprotective antibody levels was 46%. A U-shaped age distribution was identified regardless of assay or titre threshold applied. Among those less than 20 years old and those 80 years and older, the prevalence of seroprotection was comparably high at about 70%. Seroprotection was 44% among those aged 20–49 and 30% among those 50–79 years. It was lowest among people aged 70–79 years (21%) and highest among those 90 years and older (88%).

Interpretation

We measured much higher levels of seroprotection after the 2009 pandemic compared than before the pandemic, with a U-shaped age distribution now evident. These findings, particularly the low levels of seroprotection among people aged 50–79 years, should be confirmed in other settings and closer to the influenza season.In a previous age-based survey of about 1000 anonymized serum samples collected before substantial pandemic (H1N1) 2009 activity in the Lower Mainland of the province of British Columbia, Canada, we found that less than 10% of children and adults under 70 years of age had seroprotective levels of antibody against the pandemic (H1N1) virus.¹ This proportion was slightly higher among people aged 70–79 years (27%) and substantially higher among those above 80 years of age (77%).¹The 2009 influenza pandemic and the broad and effective vaccination campaign introduced major changes to this population’s immune status. The first wave in the province, in the spring and summer months, was of limited activity and was followed by a second, more substantial and widespread wave in the fall that peaked during the last week of October and resolved by the end of 2009.² Meanwhile, a highly immunogenic adjuvanted vaccine was provided free of charge through a universal vaccination campaign that targeted all Canadians.³ Supply was limited initially, requiring sequenced rollout of the vaccine, starting with children under five years of age, pregnant women, and people under 65 years who had comorbidities.⁴ The uptake of the vaccine of about 35%–45% in the province overall^4–6 and 44% in the Lower Mainland (Dr. Monika Naus, BC Centre for Disease Control, Vancouver, BC: personal communication, 2010) was estimated to be moderate compared with rates of uptake in other provinces.To assess seroprotective antibody levels after the 2009 pandemic, we repeated our age-based survey of antibody levels against the pandemic (H1N1) 2009 virus in a further 1000 serum samples collected from people in the Lower Mainland in May and June 2010, more than six months after the last peak of the epidemic.     

Immune protection induced on day 10 following administration of the 2009 A/H1N1 pandemic influenza vaccine

Background

The 2009 swine-origin influenza virus (S-OIV) H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation.

Methodology/Principal Findings

58 volunteers were vaccinated with a 2009 A/H1N1 pandemic influenza monovalent split-virus vaccine (15 µg, single-dose). The sera were collected before Day 0 (pre-vaccination) and on Days 3, 5, 10, 14, 21, 30, 45 and 60 post vaccination. Specific antibody responses induced by the vaccination were analyzed using hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). After administration of the 2009 A/H1N1 influenza vaccine, specific and protective antibody response with a major subtype of IgG was sufficiently developed as early as Day 10 (seroprotection rate: 93%). This specific antibody response could maintain for at least 60 days without significant reduction. Antibody response induced by the 2009 A/H1N1 influenza vaccine could not render protection against seasonal H1N1 influenza (seroconversion rate: 3% on Day 21). However, volunteers with higher pre-existing seasonal influenza antibody levels (pre-vaccination HI titer ≥1∶40, Group 1) more easily developed a strong antibody protection effect against the 2009 A/H1N1 influenza vaccine as compared with those showing lower pre-existing seasonal influenza antibody levels (pre-vaccination HI titer <1∶40, Group 2). The titer of the specific antibody against the 2009 A/H1N1 influenza was much higher in Group 1 (geometric mean titer: 146 on Day 21) than that in Group 2 (geometric mean titer: 70 on Day 21).

Conclusions/Significance

Recipients could gain sufficient protection as early as 10 days after vaccine administration. The protection could last at least 60 days. Individuals with a stronger pre-existing seasonal influenza antibody response may have a relatively higher potential for developing a stronger humoral immune response after vaccination with the 2009 A/H1N1 pandemic influenza vaccine.     

人群预存免疫力是2009甲型H1N1流感大流行表现温和的重要原因

历史上最具杀伤力的1918年西班牙流感大流行由H1N1亚型流感病毒引起[1],随后H1N1亚型流感继续在人群中流行,并且在20世纪20年代到50年代又引起了数次暴发[2-3]。1957年,H1N1流     

甲型H1N1流感病毒裂解疫苗的免疫原性和安全性

目的评价甲型H1N1流感病毒裂解疫苗(简称甲型H1N1流感疫苗)的免疫原性和安全性。方法按照随机、双盲、安慰剂对照的原则,采用0、21天免疫程序,选择3岁及3岁以上健康者1 202人。分组为3~11岁、12~17岁、≥60岁组,按照人数基本为1∶1的比例随机分别接种7.5μg和15.0μg甲型H1N1流感疫苗;18~59岁组按照人数基本为1∶1∶1的比例随机分别接种7.5μg、15.0μg甲型H1N1流感疫苗和安慰剂对照。观察各组接种后的不良反应率以及免疫前后血凝抑制(HI)抗体阳转率、保护率、GMT水平和平均增长倍数。结果受试对象的安全性结果显示7.5μg和15.0μg组不良反应发生率分别为8.74%(48/549)和13.88%(74/533),其中Ⅱ级反应率分别为0.36%(2/549)和1.13%(6/533),未观察到Ⅲ级及以上不良反应和其他异常反应及严重不良事件。2剂接种未见不良反应叠加现象。7.5μg或15.0μg试验疫苗首剂免疫后,血清抗体阳性率分别为85.13%(395/464)和90.77%(413/455),保护率分别为85.56%(397/464)和91.43%(416/455),抗体GMT较免疫前分别增长36.1倍和52.6倍。2剂免疫后,血清抗体阳性率分别是97.84%(454/464)和99.12%(451/455),保护率分别是98.06%(455/464)和9 9.56%(453/455),抗体GMT较免疫前分别增长63.3倍和96.0倍。4个年龄组(3~11岁、12~17岁、18~59岁及≥60岁年龄组)7.5μg和15.0μg组HI抗体阳性率和保护率均大于70%,GMT较免疫前均增长2.5倍以上,结果显示7.5μg和15.0μg甲型H1N1流感疫苗接种1剂后抗体水平已达到研究方案中设定的预期标准,免疫2剂后抗体阳性率和抗体水平明显提高。结论临床试验表明甲型H1N1流感疫苗具有良好的安全性和免疫原性,且接种1剂15.0μg甲型H1N1流感疫苗,即可在3岁和3岁以上人群中产生良好的免疫效果。     

Surface glycoproteins determine the feature of the 2009 pandemic H1N1 virus

After the outbreak of the swine-origin influenza A H1N1 virus in April 2009, World Health Organization declared this novel H1N1 virus as the first pandemic influenza virus (2009 pH1N1) of the 21^st century. To elucidate the characteristics of 2009 pH1N1, the growth properties of A/Korea/01/09 (K/09) was analyzed in cells. Interestingly, the maximal titer of K/09 was higher than that of a seasonal H1N1 virus isolated in Korea 2008 (S/08) though the RNP complex of K/09 was less competent than that of S/08. In addition, the NS1 protein of K/09 was determined as a weak interferon antagonist as compared to that of S/08. Thus, in order to confine genetic determinants of K/09, activities of two major surface glycoproteins were analyzed. Interestingly, K/09 possesses highly reactive NA proteins and weak HA cell-binding avidity. These findings suggest that the surface glycoproteins might be a key factor in the features of 2009 pH1N1. [BMB Reports 2012; 45(11): 653-658]     

Response to 2009 pandemic influenza A (H1N1) vaccine in HIV-infected patients and the influence of prior seasonal influenza vaccination

Background

The immunogenicity of 2009 pandemic influenza A(H1N1) (pH1N1) vaccines and the effect of previous influenza vaccination is a matter of current interest and debate. We measured the immune response to pH1N1 vaccine in HIV-infected patients and in healthy controls. In addition we tested whether recent vaccination with seasonal trivalent inactivated vaccine (TIV) induced cross-reactive antibodies to pH1N1. (clinicaltrials.gov Identifier:{"type":"clinical-trial","attrs":{"text":"NCT01066169","term_id":"NCT01066169"}}NCT01066169)

Methods and Findings

In this single-center prospective cohort study MF59-adjuvanted pH1N1 vaccine (Focetria®, Novartis) was administered twice to 58 adult HIV-infected patients and 44 healthy controls in November 2009 (day 0 and day 21). Antibody responses were measured at baseline, day 21 and day 56 with hemagglutination-inhibition (HI) assay. The seroprotection rate (defined as HI titers ≥1∶40) for HIV-infected patients was 88% after the first and 91% after the second vaccination. These rates were comparable to those in healthy controls. Post-vaccination GMT, a sensitive marker of the immune competence of a group, was lower in HIV-infected patients. We found a high seroprotection rate at baseline (31%). Seroprotective titers at baseline were much more common in those who had received 2009–2010 seasonal TIV three weeks prior to the first dose of pH1N1 vaccine. Using stored serum samples of 51 HIV-infected participants we measured the pH1N1 specific response to 2009–2010 seasonal TIV. The seroprotection rate to pH1N1 increased from 22% to 49% after vaccination with 2009–2010 seasonal TIV. Seasonal TIV induced higher levels of antibodies to pH1N1 in older than in younger subjects.

Conclusion

In HIV-infected patients on combination antiretroviral therapy, with a median CD4+ T-lymphocyte count above 500 cells/mm³, one dose of MF59-adjuvanted pH1N1 vaccine induced a high seroprotection rate comparable to that in healthy controls. A second dose had a modest additional effect. Furthermore, seasonal TIV induced cross-reactive antibodies to pH1N1 and this effect was more pronounced in older subjects.     

Age-matched comparison of children hospitalized for 2009 pandemic H1N1 influenza with those hospitalized for seasonal H1N1 and H3N2

BACKGROUND: A wide spectrum of clinical manifestation ranging from deaths to a mild course of disease has been reported in children infected with the 2009 pandemic H1N1 (pH1N1) influenza. METHODOLOGY/MAJOR FINDINGS: We conducted an age-matched control study comparing children hospitalized for pH1N1 with historic controls infected with seasonal H1N1 and H3N2 influenza to correct for the effect of age on disease susceptibility and clinical manifestations. We also compared children with pH1N1 to children concurrently admitted for seasonal influenza during the pandemic period to adjust for differences in health-seeking behavior during the pandemic or other potential bias associated with historic controls. There was no death or intensive care admission. Children with pH1N1 were more likely to have at least one risk condition for influenza, an underlying chronic pulmonary condition, more likely to have asthma exacerbation and to be treated with oseltamivir. There was no difference in other aspects of the clinical course or outcome. CONCLUSION: Disease manifestation of children hospitalized for pH1N1 infection was mild in our patient population.