Potency of an inactivated influenza vaccine prepared from A/duck/Mongolia/119/2008 (H7N9) against the challenge with A/Anhui/1/2013 (H7N9)

H7N9 influenza virus infection in humans was reported in China on March 31, 2013. Humans are immunologically naïve to the H7N9 subtype, for which the seasonal influenza vaccine is not effective. Thus, the development of an H7N9 influenza virus vaccine is an urgent issue. To prepare for the emergence of an influenza pandemic, we have established a library comprising more than 1300 influenza virus strains with 144 different combinations of 16 HA and 9 NA subtypes. An H7N9 virus strain isolated from a 35-year-old woman, A/Anhui/1/2013 (H7N9), was found to be antigenically similar to H7N9 influenza viruses isolated from migratory ducks. In the present study, the potency of an inactivated whole virus particle vaccine prepared from an H7N9 low pathogenic avian influenza virus, A/duck/Mongolia/119/2008 (H7N9), selected from the library, was assessed by a challenge with A/Anhui/1/2013 (H7N9). The results indicate that the test vaccine was potent enough to induce sufficient immunity to reduce the impact of disease caused by the challenge with A/Anhui/1/2013 (H7N9) in mice. The present results indicate that an inactivated whole virus particle vaccine prepared from an influenza virus strain stored in the library could be useful as a vaccine strain in case of an influenza pandemic.     

上海市长宁区不同人群H7N9禽流感知识及态度调查

目的了解上海市长宁区不同人群对H7N9禽流感的知识、态度、行为现状,为开展社区健康教育提供依据。方法运用随机整群抽样的方法在教育、企业、居民3类人群中,抽取656名人员,用自制问卷进行调查。结果长宁区居民对人感染H7N9禽流感的主要临床表现和预防措施了解不一,能够全面了解H7N9禽流感主要临床表现的只占35．67％（234／656）,只回答出其中的1个临床表现的为17．84％（117／656）。结论长宁区居民对H7N9禽流感相关知识了解不全面,应加强对居民的健康教育。     

Analysis of the immunogenicity and bioactivities of a split influenza A/H7N9 vaccine mixed with MF59 adjuvant in BALB/c mice

The H7N9 influenza virus caused significant mortality and morbidity in humans during an outbreak in China in 2013. A recombinant H7N9 influenza seed with hemagglutinin (HA) and neuraminidase (NA) gene segments from A/Zhejiang/DTID-ZJU01/2013(H7N9) and six internal protein gene segments from A/Puerto Rico/8/34(H1N1; PR8) were generated using reverse genetics. We sought to determine the immunogenic, protective properties, and mechanisms of a split avian influenza A/H7N9 vaccine mixed with MF59 adjuvant in comparison to vaccines that included other adjuvant. BALB/c mice were vaccinated with two doses of different amounts and combinations of this novel A/ZJU01/PR8/2013 split vaccine with adjuvant. Mice were subsequently challenged with A/Zhejiang/DTID-ZJU01/2013(H7N9) by intranasal inoculation. We verified that MF59 enhanced the HI, MN, and IgG antibody titers to influenza antigens. Compared with alum, MF59 could more potentially induce humoral immune responses and Th2 cytokine production after virus infection, while both MF59 and alum can slightly increase NK cell activity. This split H7N9 influenza vaccine with MF59 adjuvant could effectively induce antibody production and protect mice from H7N9 virus challenge. We have selected this vaccine for manufacture and future clinical studies to protect humans from H7N9 virus infection.     

我国6个省份全人群流感疫苗接种及认知情况调查

目的 了解调查地区全年龄组人群流感预防知识的认知及流感疫苗接种情况，探索影响流感疫苗接种的相关因素。方法 采用横断面调查设计，选择北京市、内蒙古自治区、上海市、广东省、云南省和甘肃省6个省份，通过12320卫生热线采用随机数字表拨打电话的抽样方法，于2018年3-5月开展全年龄组人群的流感防控知识、流感疫苗接种情况的电话调查，调查估计样本量为9 438人。结果 本调查应答率为46.4%（10 045/21 658），10 045名调查对象中，"流感和普通感冒有区别"的知晓率为75.3%（7 564/10 045），"流感病毒会引起严重后果"的知晓率为82.0%（8 241/10 045）。出现流感样症状后采取频繁洗手、戴口罩和自我隔离的健康行为率分别为80.4%（7 936/9 873）、75.8%（7 506/9 899）和73.6%（7 228/9 822）。最近1年流感疫苗接种率为5.7%（570/10 037）。最近1年流感疫苗接种率的相关多因素logistic回归分析结果显示，调查对象来自甘肃省或北京市、职业是医务人员或全日制学生、调查对象共同居住人数≥ 2人、出现流感样症状后戴口罩，最近1年流感疫苗接种率相对较高。结论 6个省份调查对象流感相关知识的知晓率、出现流感相关症状后的健康行为率和最近1年流感疫苗接种率均有待进一步提高。应加强流感预防知识和疫苗接种的健康教育，探索流感疫苗免费接种策略。     

Determinants of 2009 A/H1N1 Influenza Vaccination Among Pregnant Women in Hong Kong

During the 2009–2010 A/H1N1 influenza pandemic, pregnant women infected with the virus experienced excess morbidity and mortality when compared with other groups. Once a vaccine was available, pregnant women were a priority group for vaccination. Only a few studies have reported on the uptake of 2009 A/H1N1 influenza vaccine among pregnant women during the pandemic and none were from Asia. The purpose of this study was to examine factors associated with 2009 A/H1N1 influenza vaccine uptake among pregnant women in Hong Kong. Using a multi-center, cross-sectional design, we recruited 549 postpartum women from four post-natal wards in Hong Kong over a 4-month period during the second wave of the A/H1N1 influenza pandemic in the winter and spring of 2010. Only 6.2% (n = 34) of participants had received the 2009 A/H1N1 influenza vaccine and 4.9% (n = 27) had received the seasonal influenza vaccine. The most common reasons for not receiving the 2009 A/H1N1 vaccine were fear of causing harm to themselves or their fetus. A high knowledge level (OR = 19.06; 95% CI 5.55, 65.48), more positive attitudes (OR = 3.52; 95% CI 1.37, 9.07), and having a family member who had the 2009 A/H1N1 influenza vaccine (OR = 7.69; 95% CI 2.92, 20.19) were independently and positively associated with vaccination. Study results show an unacceptably low uptake of the pandemic A/H1N1 influenza vaccine among pregnant women in Hong Kong. Interventions to increase influenza vaccine knowledge and uptake among this group should be a priority for future pandemic planning and seasonal vaccination campaigns.     

北京市昌平区3种人群对人感染H7N9禽流感知识、心理、行为状况调查

目的了解北京市昌平区不同人群对人感染H7N9禽流感的认知、心理、行为状况和对政府实施措施的满意度情况。方法制定统一调查表,随机抽取2013年4月食品从业人员、学生和社区居民共670人,采取当场自填式和个别面对面询问相结合的问卷调查。结果95．4％的人知道北京市出现了人感染H7N9禽流感疫情;有75．6％的调查对象对政府采取措施感到满意;有44．5％的人对疫情动态比较关注;对发生人感染H7N9禽流感有47．8％的人有点紧张,紧张的原因中有47．3％的人担心疫情扩大;在6项人感染H7N9禽流感相关知识中,食品从业人员有3项回答正确率较高,学生有3项回答正确率较高,居民有I项回答正确率较高。有23．9％的调查人群在北京市发生人感染H7N9禽流感疫情后有行为改变,其中以社区居民行为改变率最高。获得禽流感知识的渠道以电视（90．9％）和网络（76．3％）为主。结论昌平区不同人群对人感染H7N9禽流感有较高的认知度,但部分人群表现对人感染H7N9禽流感的紧张情结。应继续加大对人感染H7N9禽流感防治知识的宣传和培训力度,正确引导媒体舆论,防止因对人感染H7N9禽流感疫情认识不足而引起社会恐慌。     

H7N3 live attenuated influenza vaccine has a potential to protect against new H7N9 avian influenza virus

After recent emergence of new avian influenza A(H7N9) viruses in humans many people and Governments are asking about H7 influenza vaccine which could provide cross-protection against new viruses, until H7N9 vaccine is prepared from a relevant strain. Here we scientifically justify that available H7N3 live attenuated influenza vaccine (LAIV) can be protective against H7N9 viruses due to the presence of conserved immune epitopes in its hemagglutinin. We used Immune Epitope Database analysis resource to predict B-cell and CTL epitopes distributed across H7N3 HA molecule and assessed their identity with new H7N9 viruses at near 70% and 60% of the epitopes, respectively. In addition, we tested serum samples of volunteers participated in phase I clinical trial of H7N3 LAIV for the presence of anti-H7N9 hemagglutination-inhibition and neutralizing antibodies and found seroconversions in 44.8% of vaccinated persons, which suggests the potential of H7N3 LAIV to protect against new H7N9 avian influenza viruses.     

Genetic characterization and protective immunity of cold-adapted attenuated avian H9N2 influenza vaccine

H9N2 influenza viruses are endemic in many Asian countries including China and Korea, and cause a considerable economic loss to chicken industry by reduction in egg production and about 30% mortality. Here we developed live cold-adapted attenuated H9N2 influenza vaccine by adaptation of viruses in hen's eggs at 25 degrees C. Genetic analysis shows that the cold-adapted H9N2 (A/Chicken/Korea/S1/03) viruses contain a total of 44 amino acid substitutions, of which 7 amino acids are identical to the loci identified in the cold-adapted H2N2 (A/Ann Arbor/6/60) vaccine strain compared to genes in wild-type H9N2 (A/Chicken/Korea/S1/03) influenza viruses. When cold-adapted H9N2 (A/Chicken/Korea/S1/03) influenza viruses were inoculated in layers viruses were detectable in the tracheas, not in the lungs, no reduction of egg production and mortality was observed in contrast to the infection of wild-type H9N2 influenza viruses, and CD8+ T lymphocytes expressing IFN-gamma were induced. When layers vaccinated with cold-adapted attenuated H9N2 (A/Chicken/Korea/S1/03) influenza viruses were challenged with wild-type H9N2 (A/Chicken/Korea/521/04) influenza viruses, they were protected from the loss of egg production and mortality. Our results suggest that cold-adapted attenuated H9N2 vaccine can be used for controlling the infection of H9N2 influenza viruses in chickens.     

Generation and evaluation of the trivalent inactivated reassortant vaccine using human, avian, and swine influenza A viruses

Reassortant technology was used to obtain three interspecific reassortant influenza viruses using three influenza viruses of A/Puerto Rico/8/34(H1N1), A/swine/Hebei/1/2005(H3N2) and A/chicken/Guangdong/126/2002(H9N2). The high-growth reassortant strains were H9/PR8, H3/H9N2 and H1/H9N2 that contained hemagglutinin (HA) and neuraminidase (NA) genes from the inactivated parental viruses and the other 6 internal genes from the live parental viruses. The trivalent formalin-inactivated vaccine, containing H1, H3 and H9 subtype antigens from human, swine and avian influenza viruses respectively, was prepared using these reassortant viruses. Animal studies showed that the vaccine was safe and immunogenic. Two-dosing regimen of the influenza vaccine induced high titers of hemagglutination inhibiting (HI) antibodies and influenza-specific IgG antibodies without antigenic cross-interference. It protected 100% chickens from challenge of A/chicken/Guangdong/126/2002 virus and protected 100% mice against challenges with different combinations of the three infective parental viruses. These results indicated that the trivalent vaccine could offer multi-protection against multi-influenza viruses synchronously. This kind of multivalent inactivated reassortant influenza vaccine maybe enlightens the pandemic influenza preparedness as the emergency measure.     

北京市普通人群甲型H1N1流感病毒血清抗体阳性影响因素的病例对照研究

目的探讨影响北京市普通人群血清甲型H1N1流感病毒抗体阳性的因素。方法按1∶1配对的病例对照研究设计,采用问卷调查方法,收集65例血清甲型H1N1流感病毒抗体阳性病例和65例阴性对照者的人口统计学特征、疫苗接种史,卫生习惯等信息。结果单因素分析显示,疫苗接种史、旅游史、调查前曾出现流感样症状、周围有确诊的甲型H1N1流感患者、调查前曾去医院发热门诊、勤洗手习惯等与血清甲型H1N1流感病毒抗体阳性有关。多因素条件Logistic回归分析结果表明,甲型H1N1流感病毒疫苗接种史（OR=4.82,95%CI：1.23-19.91）、调查前1月内曾出现过流感样症状（OR=2.53,95%CI：1.01-6.25）,勤洗手习惯（OR=0.21,95%CI：0.06-0.74）等3个因素与血清甲型H1N1流感病毒抗体阳性有关。结论甲型H1N1流感疫苗接种史、旅游史、曾出现流感样症状、曾与确诊的甲型H1N1流感患者接触、勤洗手习惯等与血清甲型H1N1流感病毒抗体阳性有关。提示应当继续推行甲型H1N1流感疫苗的接种,加强手卫生等一般措施是预防甲型H1N1流感的重要手段。     

Protection against H1, H5, H6 and H9 influenza A infection with liposomal matrix 2 epitope vaccines

The recent emergence of multiple avian influenza A subtypes that cause human disease (i.e., H5N1, H9N2 and H7N7), coupled with the fear that one of these strains might precipitate a new pandemic, underscores the need to develop new technological approaches to immunization which elicit protective immune responses against multiple subtypes of influenza A. In response to this demand, several matrix 2 protein ectodomain segments (M2eA) corresponding to the H1N1, H5N1 and H9N2 influenza strains were formulated using a novel liposome-based vaccine technology and evaluated as potential immunogens for developing a "universal" influenza vaccine. Mice immunized with liposomal M2eA survived homologous challenges with H1N1 (100% survival) or H9N2 (80% survival) influenza strains. There were significant reductions in their lung viral load as well as in immunized mice challenged with the H5N1 subtype. The mice vaccinated with an M2eA segment corresponding to the H1N1 and H6N2 (a reassortant influenza A virus carrying the M2eA from PR8/34) strains elicited elevated IgG ELISA antibody titers to this M2eA epitope segment and antiserum from these immunized mice provided passive protection (100% survival) to na?ve mice receiving a lethal dose of H6N2 influenza virus. These results provide the first evidence that recombinant M2eA epitopes to multiple subtypes elicited immune protection against a homologous challenge and provides further evidence in favor of the development of a "universal" influenza vaccine based on M2eA.     

Human Exposure to Live Poultry and Psychological and Behavioral Responses to Influenza A(H7N9), China

To investigate human exposure to live poultry and changes in risk perception and behavior after the April 2013 influenza A(H7N9) outbreak in China, we surveyed 2,504 urban residents in 5 cities and 1,227 rural residents in 4 provinces and found that perceived risk for influenza A(H7N9) was low. The highest rate of exposure to live poultry was reported in Guangzhou, where 47% of those surveyed reported visiting a live poultry market >1 times in the previous year. Most (77%) urban respondents reported that they visited live markets less often after influenza A(H7N9) cases were first identified in China in March 2013, but only 30% supported permanent closure of the markets to control the epidemic. In rural areas, 48% of respondents reported that they raised backyard poultry. Exposure to live commercial and private poultry is common in urban and rural China and remains a potential risk factor for human infection with novel influenza viruses.     

A highly immunogenic vaccine against A/H7N9 influenza virus

Since the first case of human infection in March 2013, continued reports of H7N9 cases highlight a potential pandemic threat. Highly immunogenic vaccines to this virus are urgently needed to protect vulnerable populations who lack protective immunity. In this study, an egg- and adjuvant-independent adenoviral vector-based, hemagglutinin H7 subtype influenza vaccine (HAd-H7HA) demonstrated enhanced cell-mediated immunity as well as serum antibody responses in a mouse model. Most importantly, this vaccine provided complete protection against homologous A/H7N9 viral challenge suggesting its potential utility as a pandemic vaccine.     

Safety and immunogenicity of an 8 year interval heterologous prime-boost influenza A/H7N7-H7N9 vaccination

Background

Influenza A/H7N9 viruses are undergoing antigenic drift since their emergence in 2013, and vaccination strategies are needed for pandemic preparedness. Two doses of adjuvanted monovalent inactivated influenza A/H7N9 vaccine (IIV1 A/H7N9) are needed for optimal serological responses. However, administering 2 doses in a pandemic setting might be challenging. We evaluated the immunogenicity of “boosting” with IIV1 A/H7N9 in subjects “primed” 8?years previously with IIV1 A/H7N7.

Microbial adaptation and change: avian influenza

The evolution of influenza is a continuing process involving viral and host factors. The increasing frequency of emergence of the highly pathogenic H5N1, H7N3 and H7N7 influenza viruses and the panzootic spread of H9N2 influenza virus, all of which can be potentially transmitted to humans, are of great concern to both veterinary and human public health officials. The question is how soon the next pandemic will emerge. A convergence of factors, including the population densities of poultry, pigs and humans, are likely factors affecting the evolution of the virus. Highly concentrated poultry and pig farming, in conjunction with traditional live animal or 'wet' markets, provide optimal conditions for increased mutation, reassortment and recombination of influenza viruses. Strategies to reduce the evolution of influenza and the emergence of pandemics include the separation of species, increased biosecurity, the development of new vaccine strategies and better basic knowledge of the virus. More effective co-operation between scientists and veterinary and public health officials is required to achieve these goals.     

A vaccine prepared from a non-pathogenic H7N7 virus isolated from natural reservoir conferred protective immunity against the challenge with lethal dose of highly pathogenic avian influenza virus in chickens

During 2001-2004, 41 H7 influenza viruses (2 H7N1 and 39 H7N7 strains) were isolated from fecal samples of migratory ducks that flew from Siberia in the autumn of each year to Japan and Mongolia. A phylogenetic analysis of the hemagglutinin (HA) genes of the nine representative isolates revealed that they belonged to the Eurasian lineage and the deduced amino acid sequence at the cleavage site of the HAs represented apathogenic profiles. One of the H7 isolates A/duck/Mongolia/736/02 (H7N7) was chosen from these H7 isolates for the preparation of the test vaccine. To improve the growth potential of A/duck/Mongolia/736/02 (H7N7) in chicken embryos, A/duck/Hokkaido/Vac-2/04 (H7N7) was generated by genetic reassortment between A/duck/Mongolia/736/02 (H7N7) as the donor of the PB2, PB1, PA, HA, NA, and NS genes and A/duck/Hokkaido/49/98 (H9N2) as that of NP and M genes. The test vaccine was prepared as follows; A/duck/Hokkaido/Vac-2/04 (H7N7) was propagated in chicken embryos and the virus in the allantoic fluid was inactivated and adjuvanted to form an oil-in-water emulsion. The test vaccine conferred immunity to chickens, completely protecting the manifestation of clinical signs against the challenge with lethal dose of H7 highly pathogenic avian influenza virus. These results indicate that influenza viruses isolated from natural reservoirs are useful for vaccine strains.     

Avian influenza A (H7N9) virus infection in humans: Epidemiology,evolution, and pathogenesis

New human influenza A virus strains regularly emerge causing seasonal epidemics and occasional pandemics. Lately, several zoonotic avian influenza A strains have been reported to directly infect humans. In early 2013, a novel avian influenza A virus (H7N9) strain was discovered in China to cause severe respiratory disease in humans. Since then, over 450 human cases of H7N9 infection have been discovered and 165 of them have died. Multiple epidemiological, phylogenetic, in vivo, and in vitro studies have been done to determine the origin and pathogenesis of novel H7N9 strain. This article reviews the literature related to the epidemiology, evolution, and pathogenesis of the H7N9 strain since its discovery in February 2013 till August 2014. The data available so far indicate that H7N9 was originated by a two-step reassortment process in birds and transmitted to humans through direct contact with live-bird markets. H7N9 is a low-pathogenic avian virus and contains several molecular signatures for adaptation in mammals. The severity of the respiratory disease caused by novel H7N9 virus in humans can be partly attributed to the age, sex, and underlying medical conditions of the patients. A universal influenza vaccine is not available, though several strain-specific H7N9 candidate vaccine viruses have been developed. Further, novel H7N9 virus is resistant to antiviral drug amantadine and some H7N9 isolates have acquired the resistance to neuraminidase-inhibitors. Therefore, constant surveillance and prompt control measures combined with novel research approaches to develop alternative and effective anti-influenza strategies are needed to overcome influenza A virus.     

Intranasal seasonal influenza vaccine and a TLR-3 agonist,rintatolimod, induced cross-reactive IgA antibody formation against avian H5N1 and H7N9 influenza HA in humans

The intranasal use of rintatolimod, a specific TLR-3 agonist, combined with trivalent seasonal influenza vaccine generated cross-protection against highly pathogenic H5N1 avian influenza in mice. The purpose of this clinical trial is to assess the safety and impact of rintatolimod on intranasal influenza vaccine in healthy adults. During Stage I of this Phase I/II clinical trial, 12 volunteers were immunized intranasally with 3 doses of FluMist^® seasonal influenza vaccine on Days 0, 28, and 56 followed by intranasal rintatolimod (50 μg, 200 μg, or 500 μg) 3 days later. Parotid saliva and nasal wash samples were collected at baseline and on Days 25, 53, 84, and 417. The samples were tested for IgA and IgG specific antibodies (Ab) directed against the homologous FluMist^® viral hemagglutinins (HAs). In addition, viral specific responses against influenza A HAs were tested for IgA Ab cross-reactivity against 3 H5 clades: HA (H5N1) A/Indonesia/5/2005, HA (H5N1) A/Hong Kong/483/97 and HA (H5N1) A/Vietnam/1194/2004, as well as, two H7 strains, HA (H7N9) A/Shanghai/2/2013 and HA (H7N3) A/chicken/Jalisco/CPA1. The combination of the intranasal FluMist^® along with the rintatolimod generated specific secretory IgA responses of at least 4-fold over baseline against at least one of the homologous vaccine strains included in the vaccine in 92% of the vaccinees. Additionally, this vaccination strategy induced cross-reactive secretory IgA against highly pathogenic avian influenza virus strains H5N1, H7N9, and H7N3 with pandemic potential for humans. The combination of rintatolimod and FluMist^® was well-tolerated.     

Estimating efficacy of trivalent,cold-adapted,influenza virus vaccine (CAIV-T) against influenza A (H1N1) and B using surveillance cultures

The authors report on a community-based, nonrandomized, open-label study, conducted during the 2000-2001 influenza season in Temple-Belton, Texas, of the protective effectiveness of trivalent, cold-adapted, influenza virus vaccine (CAIV-T) in children aged 18 months-18 years. The dominant circulating strains in 2000-2001 were influenza A/New Caledonia/20/99 (H1N1) and influenza B/Sichuan/379/99. Children had access to CAIV-T during the 1998-1999, 1999-2000, and 2000-2001 influenza seasons. The vaccine included influenza A/Sydney/5/97 (H3N2) and B/Beijing/184/93-like (B/Ann Arbor/l/94) strains in all three seasons. The vaccine included A/Beijing/262/95 (H1N1) in 1998-1999 and 1999-2000, which was replaced by A/New Caledonia/20/99 (H1N1) in 2000-2001. When medically attended acute respiratory illness (MAARI) was used as the outcome, the protective effectiveness for children vaccinated in 2000 was 18% (95% confidence interval (CI): 11, 25). Based on a combination of a validation sample of surveillance cultures and the MAARI outcome, protective efficacy against combined influenza A (H1N1) and B was 79% (95% CI: 51, 91). The efficacy estimate, after accounting for missing influenza culture status, against influenza A (H1N1) alone was 92% (95% CI: 42, 99) and against a new variant of influenza B alone was 66% (95% CI: 9, 87). CAIV-T provides substantial protection against a mixture of influenza A (H1N1) and B. Results demonstrate the powerful potential of using validation sets for outcomes in vaccine field studies.     

Vaccination against pandemic influenza A/H1N1 among healthcare workers and reasons for refusing vaccination in Istanbul in last pandemic alert phase

Coverage of the HCWs as target population is one of the important determinants for the impact of vaccination. To determine the vaccination against the pandemic influenza A/H1N1 among HCWs, we conducted a cross-sectional questionnaire survey in a public hospital in Istanbul from December 7 to December 22, 2009. Out of total 941 HCWs 718 (76.3%) completed the questionnaires. Nearly one-fourth (23.1%) of the participants were vaccinated against pandemic influenza A/H1N1. Occupation (being a doctor), receiving seasonal influenza vaccine in 2009, agreement with safety of pandemic influenza A/H1N1 vaccine and being comprehend that HCWs have a professional responsibility for getting vaccinated was the strongest independent predictive factor for accepting the pandemic influenza A/H1N1 vaccine (p < .0001). The most frequent reasons for refusing pandemic vaccine were fear of side effects and doubts about vaccine efficacy. Among HCWs 59.6% were recommending pandemic influenza vaccination to a patient even if indicated. In conclusion vaccination against pandemic influenza A/H1N1 is insufficient among HCWs. Misinformed or inadequately informed HCWs are important barrier to pandemic influenza vaccine coverage of the general public also. Educational campaigns concerning HCWs should include evidence based and comprehensible information about possible adverse effects and their incidence besides the advantages of vaccine.