The long road of pandemic vaccine development to rollout: A systematic review on the lessons learnt from the 2009 H1N1 influenza pandemic.

BACKGROUND: The 2009 Influenza A(H1N1) pandemic prompted one of the largest public health responses in history. The continuous emergence of new and deadly pathogens has highlighted the need to reflect upon past experiences to improve pandemic preparedness. The aim of this study was to examine the development and rollout of 2009 influenza A(H1N1) pandemic vaccine and knowledge challenges for the effective implementation of vaccination programs for COVID-19 and future influenza pandemics. METHODS: A systematic review was conducted searching EMBASE (inception to current date) and PUBMED (from January 2009 to current date) databases for relevant published studies about influenza A(H1N1) pandemic vaccines. A Google search was conducted to identify relevant documents from gray literature. Selected Studies were reviewed and summarized. RESULTS: A total of 22, comprising of 12 original studies and 10 relevant documents met the inclusion criteria. Fourteen papers reported an initial high demand that outweighed production capacity and caused vaccine shortages. Vaccine procurement and supply were skewed toward high-income countries. Low vaccination rates of about 5%-50% were reported in all studies mainly due to a low-risk perception of getting infected, safety concerns, and the fear of adverse effects. CONCLUSIONS: Safety concerns about the approved H1N1 vaccines resulted in many unsuccessful vaccination campaigns worldwide. Understanding the factors that influence people's decision to accept or refuse vaccination, effective risk communication strategies, adequate resources for vaccine deployment initiatives and building local capacities through shared knowledge and technology transfer may help to improve COVID-19 vaccine uptake and accelerate pandemic control.

Disparities in H1N1 Vaccination Rates: a Systematic Review and Evidence Synthesis to Inform COVID-19 Vaccination Efforts.

BACKGROUND: Data suggest that there were disparities in H1N1 vaccine uptake, and these may inform COVID-19 vaccination efforts. We conducted a systematic review to evaluate disparities in H1N1 vaccine uptake, factors contributing to disparities, and interventions to reduce them. METHODS: We searched English-language articles in MEDLINE ALL, PsycINFO, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from database inception through May 8, 2020. Observational studies examining H1N1 vaccine uptake by race/ethnicity, socioeconomic status, rurality, and disability status in US settings were included. Two reviewers independently assessed study eligibility. Single-reviewer data abstraction was confirmed by a second reviewer. We conducted independent dual quality assessment, and collective strength of evidence assessment. RESULTS: We included 21 studies. African American/Black, Latino, and low-socioeconomic status participants had disproportionately lower H1N1 vaccination rates (low- to moderate-strength evidence). However, Latinos were more likely than Whites to intend to be vaccinated, and African American/Blacks and participants with lower-socioeconomic status were just as likely to intend to be vaccinated as their White and higher-socioeconomic status counterparts (low-strength evidence). Vaccine uptake for other groups has been insufficiently studied. Factors potentially contributing to disparities in vaccine uptake included barriers to vaccine access, inadequate information, and concerns about vaccine safety and efficacy. Studies were largely cross-sectional. Many of the studies are a decade old and were conducted in the context of a different pandemic. The categorization of racial and ethnic groups was not consistent across studies and not all groups were well-studied. DISCUSSION: Efforts to avoid disparities in COVID-19 vaccination uptake should prioritize vaccine accessibility and convenience in African American/Black, Latino, and low-SES communities; engage trusted stakeholders to share vaccine information; and address concerns about vaccine safety and efficacy. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. PROTOCOL REGISTRATION: PROSPERO CRD42020187078.

Anti-NMDA Receptor Encephalitis, Vaccination and Virus.

Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune disorder. The symptoms range from psychiatric symptoms, movement disorders, cognitive impairment, and autonomic dysfunction. Previous studies revealed that vaccination might induce this disease. A few cases were reported to be related to H1N1 vaccine, tetanus/diphtheria/pertussis and polio vaccine, and Japanese encephalitis vaccine. Although vaccination is a useful strategy to prevent infectious diseases, in a low risk, it may trigger serious neurological symptoms. In addition to anti-NMDA receptor encephalitis, other neurological diseases were reported to be associated with a number of vaccines. In this paper, the anti-NMDA receptor encephalitis cases related to a number of vaccines and other neurological symptoms that might be induced by these vaccines were reviewed. In addition, anti-NMDA receptor encephalitis cases that were induced by virus infection were also reviewed.

Impact of H1N1 Influenza Vaccination on Child Morbidity in Guinea-Bissau.

BACKGROUND: In addition to vaccines' specific effects, vaccines may have non-specific effects (NSEs) altering the susceptibility to unrelated infections. Non-live vaccines have been associated with negative NSEs. In 2010, a campaign with the non-live H1N1-influenza vaccine targeted children 6-59 months in Guinea-Bissau. METHODS: Bandim Health Project runs a health and demographic surveillance system site in Guinea-Bissau. Using a Cox proportional hazards model, we compared all-cause consultation rates after vs. before the campaign, stratified by participation status. RESULTS: Among 10 290 children eligible for the campaign, 60% had participated, 18% had not and for 22% no information was obtained. After the H1N1 campaign, the consultation rates tended to decline less for participants [HR = 0.80 (95% confidence interval, CI: 0.75; 0.85)] than for non-participants [HR = 0.68 (95% CI: 0.58; 0.79)], p = 0.06 for same effect. CONCLUSION: The decline in the vaccinated group may have been smaller than the decline in the non-vaccinated group consistent with H1N1-vaccine increasing susceptibility to unrelated infections.

A pilot study using a novel pyrotechnically driven prototype applicator for epidermal powder immunization in piglets.

Epidermal powder immunization (EPI) is an alternative technique to the classical immunization route using needle and syringe. In this work, we present the results of an in vivo pilot study in piglets using a dried influenza model vaccine which was applied by EPI using a novel pyrotechnically driven applicator. A liquid influenza vaccine (Pandemrix®) was first concentrated by tangential flow filtration and hemagglutinin content was determined by RP-HPLC. The liquid formulation was then transformed into a dry powder by collapse freeze-drying and subsequent cryo-milling. The vaccine powder was attached to a membrane of a novel pyrotechnical applicator using oily adjuvant components. Upon actuation of the applicator, particles were accelerated to high speed as determined by a high-speed camera setup. Piglets were immunized twice using either the novel pyrotechnical applicator or classical intramuscular injection. Blood samples of the animals were collected at various time points and analyzed by enzyme-linked immunosorbent assay. Our pilot study shows that acceleration of a dried vaccine powder to supersonic speed using the pyrotechnical applicator is possible and that the speed and impact of the particles is sufficient to breach the stratum corneum of piglet skin. Importantly, the administration of the dry vaccine powder resulted in measurable anti-H1N1 antibody titres in vivo.

Recurrent pityriasis rosea: A case report.

Pityriasis rosea is a papulosquamous skin disorder that occurs most commonly between the ages of 10 and 35 years. Recurrent pityriasis rosea is rare. We report a patient suffering from recurrent pityriasis rosea, whose etiology may be related to either vaccine-induced stimulation of the immune system, or some rare vaccine component(influenza A [H1N1] vaccine, hepatitis B vaccine). We believe that such a case is unique and it has not been reported previously. The patient was successfully treated with a combination of oral cetirizine, a topical steroid cream, and narrowband-ultraviolet B phototherapy. The symptoms of this disorder should be recognized by dermatologists.

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

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

Spontaneous reporting of suspected narcolepsy after vaccination against pandemic influenza A (H1N1) in Germany.

PURPOSE: We aimed at investigating whether, in Germany, the number of individual case safety reports (ICSR) of confirmed narcolepsy following Pandemrix® vaccination notified to the Paul-Ehrlich-Institut (PEI, German Federal Institute for Vaccines and Biomedicines) was higher than expected when compared with the prepandemic background incidence rates. METHODS: ICSR of narcolepsy after vaccination with Pandemrix® notified to the PEI until September 2016 were reviewed and validated according to the criteria of narcolepsy defined by the Brighton Collaboration (BC). Cases fulfilling the criteria of BC levels of diagnostic certainty 1 to 4a with symptoms onset after vaccination with Pandemrix® were eligible. Adjustment for underreporting was performed with cases of narcolepsy recruited within the scope of the German Narcolepsy Study using capture-recapture methods. An observed versus expected (OvE) analysis was conducted based on adjusted case numbers using risk windows for symptoms onset within 4 and 6 months following vaccination. RESULTS: By the end of September 2016, a total of 85 ICSR of narcolepsy after vaccination with Pandemrix® had been notified to the PEI 52 of which were eligible. The OvE estimates for the 4 and 6 months risk windows were 3.8 (95% CI: 2.6-5.4) and 2.8 (95% CI: 2.0-3.9), respectively. The number of excess cases was higher in children and adolescents (15-fold and 11.7-fold increased OvE estimate) than in adults (2.1-fold and 1.5-fold increased estimate). CONCLUSIONS: Compared with the prepandemic background incidence rate, the number of incident narcolepsy cases was 3.8-fold and 2.8-fold as high.

Caspase 3 role and immunohistochemical expression in assessment of apoptosis as a feature of H1N1 vaccine-caused Drug-Induced Liver Injury (DILI).

BACKGROUND: Drug-Induced Liver Injury (DILI) changes, occur post exposure to natural or chemical compounds including apoptosis. AIM: To assess the H1N1 vaccine-caused DILI by histochemical and immunohistochemical methods. METHODS: This 2014's experimental study was conducted on 70 albino rats. They were given ArepanrixTM H1N1 vaccine and were divided into 7 groups; 10 mice each, as control (non-vaccinated), vac2 and vac4 injected with 1st and 2nd doses of vaccine (suspension only) and euthanized after 3 weeks each, vac5 euthanized 6 weeks after 2nd dose, mix2 and mix4 injected with 1st and 2nd doses of vaccine (mixture of suspension and adjuvant) and euthanized after 3 weeks each, mix5 and euthanized 6 weeks after 2nd dose. Histopathological evaluation and histochemical assessment of metabolic protein, glycogen and collagen changes using PAS, bromophenol blue, Mallory's trichrome and immunohistochemistry for caspase 3 on liver tissue paraffin sections were done. Image analysis system Leica QIIN 500 was used. Data were analyzed by SPSS software, using descriptive statistics and ANOVA. RESULTS: Histopathological changes ranging from subtle up to necrosis were noticed, mainly in mix groups. Metabolic protein and glycogen changes were the maximum in mix5 group (p<0.01). Collagen deposition in sinusoids was higher in mix groups, and maximally in vac5 and mix5. Apoptotic hepatocytes expressing diffuse strong nuclear and cytoplasmic caspase 3 were the highest in mix5. CONCLUSION: H1N1 vaccine can cause DILI by either direct toxic or idiosyncratic metabolic type reactions rather than immunologic hypersensitivity type. It ranges from subtle changes up to necrosis. Caspase 3 is pivotal in liver damage etiology, apoptosis induction and processing. Follow up for at least 2 months after the 2nd dose of H1N1 vaccine is recommended to rule out H1N1-induced DILI.

Distinct patterns of cellular immune response elicited by influenza non-adjuvanted and AS03-adjuvanted monovalent H1N1(pdm09) vaccine.

The study aimed at identifying biomarkers of immune response elicited by non-adjuvanted-(NAV) and adjuvanted-(AV) H1N1(pdm09) vaccines. The results showed that despite both vaccines elicited similar levels of anti-H1N1 antibodies at day30 after vaccination, higher reactivity was observed in AV at day180. While AV induced early changes in cell-surface molecules on monocytes, CD4+, CD8+ T-cells and B-cells, NAV triggered minor changes, starting later on at day3. Furthermore, AV induced a late and persistent increase in TLR gene expression after day3, except for tlr4, while NAV displayed earlier but transient tlr3/4/7/9 up-regulation. Contrasting with NAV, prominent chemokine gene expression (cxcl8,cxcl9,ccl5) and a broad spectrum up-regulation of plasmatic biomarkers (CXCL8,IL-6,IL-1ß,IL-12,IL-10) was evident in AV, which showed a major involvement of TNF and IL-10. Similarly, AV induced a robust IL-10-modulated proinflammatory storm, with early and persistent involvement of TNF-α/IL-12/IFN-γ axis derived from NK-cells, CD4+ and CD8+ T-cells along with promiscuous production of IL-4/IL-5/IL-13. Conversely, NAV promotes a concise and restricted intracytoplasmic chemokine/cytokine response, essentially mediated by TNF-α and IL-4, with late IL-10 production by CD8+ T-cells. Systems biology approach underscored that AV guided the formation of an imbricate network characterized by a progressive increase in the number of neighborhood connections amongst innate and adaptive immunity. In AV, the early cross-talk between innate and adaptive immunity, followed by the triad NK/CD4+/CD8+ T-cells at day3, sponsored a later/robust biomarker network. These findings indicate the relevance of adjuvanted vaccination to orchestrate broad, balanced and multifactorial cellular immune events that lead ultimately to a stronger H1N1 humoral immunity.

Characterization of naive and memory T cell after immunization with H1N1 influenza vaccine for children / 中国免疫学杂志

Objective:To elucidate the characterization of CD8+T cell in H1N1 influenza vaccine for children.Methods:PBMCs were isolated from 31 children aged from 3 to 6 years old who had accepted H 1N1 influenza vaccine during December 2009 to January 2010.The lymphocytes were joined with the H 1N1 influenza vaccine as experimental group and cultured .The experiment set without vaccine group as control group .At last we detected the surface molecules by FCM .The CCK-8 assay was added to detecting cellular proliferation and cellular proliferation index were detected by CCK-8.Results: CD8+T cells of PBMC in the two groups were 13.41%and 9.41%,P>0.05.CD8+CD45RAA+naive T cells in the two groups were up to more than 80%,P>0.05.The proportion of CD8+CD45ROA+memory T cells in two groups were up to 17%-19%,P>0.05.Two subsets of CD8+CD45ROA+memory T cells :CCR7+and CD62L+single positive memory T cell subsets in the experimental group were significantly lower than that of the control group,P<0.05.The CCK-8 assay was added to detect cellular proliferation .Only 51.16% of which cellular proliferation index was greater than 0.8,with none was greater than 1 in this study.Conclusion:This study showed that the CD4+T cells were low-level,naive T cells (CD8+CD45RAA+)were higher,with antigen stimulation and response.H1N1 vaccination specific memory T cells were few in number , specific memory T cell subsets were diversity , control memory cells were the main phenotypic characteristics .Cellular proliferation index showed that the proliferation of specific CD 8+T cells vaccine was poor .

Fetal death and preterm birth associated with maternal influenza vaccination: systematic review.

BACKGROUND: Before 2012, few studies had addressed pregnancy outcomes following maternal influenza vaccination; however, the number of publications on this topic has increased recently. OBJECTIVES: To review comparative studies evaluating fetal death or preterm birth associated with influenza vaccination during pregnancy. SEARCH STRATEGY: We searched bibliographic databases from inception to April 2014. SELECTION CRITERIA: Experimental or observational studies assessing the relationship between influenza vaccination during pregnancy and fetal death or preterm birth. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data from studies meeting the inclusion criteria. MAIN RESULTS: We included one randomised clinical trial and 26 observational studies. Meta-analyses were not considered appropriate because of high clinical and statistical heterogeneity. Three studies of fetal death at any gestational age reported adjusted effect estimates in the range 0.56-0.79, and four of five studies of fetal death at <20 weeks reported adjusted estimates between 0.89 and 1.23, all with confidence intervals including 1.0. Adjusted effect estimates for four of five studies of fetal death at ≥20 weeks ranged from 0.44 to 0.77 (two with confidence intervals not crossing 1.0), whereas a fifth reported a non-significant effect in the opposite direction. Among 19 studies of preterm birth, there was no strong evidence suggesting any increased risk, and meta-regression did not explain the moderate between-study heterogeneity (I(2) = 57%). AUTHORS' CONCLUSIONS: Most studies reported no association between fetal death or preterm birth and influenza vaccination during pregnancy. Although several reported risk reductions, results may be biased by methodological shortcomings of observational studies of influenza vaccine effectiveness.

A/H1N1 vaccine intentions in college students: an application of the theory of planned behavior.

OBJECTIVE: To test the applicability of the Theory of Planned Behavior (TPB) in college students who have not previously received the A/H1N1 vaccine. PARTICIPANTS: Undergraduate communication students at a metropolitan southern university. METHODS: In January-March 2010, students from voluntarily participating communication classes completed a hardcopy survey assessing TPB and clinically significant constructs. Hierarchical regression equations predicted variance in vaccine intentions of students who had not received a flu shot (N=198; 70% Caucasian). RESULTS: The TPB model explained 51.7% (p<.001) of variance in vaccine intentions. Controlling for side effects, self-efficacy and perceived comparative susceptibility predicted intentions when entered in the first block, whereas attitudes, subjective norms, and perceived behavioral control significantly contribute when entered in the second block. CONCLUSIONS: For students who have not previously received a flu vaccine, vaccine communication should utilize self-efficacy and perceived comparative susceptibility to employ the TPB to promote vaccine intentions.

Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: exposure prevalence, preterm delivery, and specific birth defects.

UNLABELLED: We estimated exposure prevalence and studied potential risks for preterm delivery (PTD) and specific birth defects associated with exposure to the unadjuvanted pH1N1-containing vaccines in the 2009-2010 and 2010-2011 influenza seasons. We used data from 4 regional centers in the United States collected as part of the Slone Epidemiology Center's Birth Defects Study. For PTD, propensity score-adjusted time-varying hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for exposure anytime in pregnancy and for each trimester. For 41 specific major birth defects, propensity score-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Among 4191 subjects, there were 3104 mothers of malformed (cases) and 1087 mothers of nonmalformed (controls). Exposure prevalences among controls were 47% for the 2009-2010 season and 38% for the 2010-2011 season; prevalence varied by geographic region. Results for PTD differed between the two seasons, with risks above and below the null for the 2009-2010 and 2010-2011 seasons, respectively. For 41 specific birth defects, most adjusted ORs were close to 1.0. Three defects had adjusted ORs>2.0 and four had risks<0.5; however, 95% CIs for these were wide. CONCLUSIONS: Among women exposed to pH1N1 vaccine, we found a decreased risk for PTD in the 2010-2011 season; risk was increased in 2009-2010, particularly following exposure in the first trimester, though the decrease in gestational length was less than 2 days. For specific major defects, we found no meaningful evidence of increased risk for specific congenital malformations following pH1N1 influenza vaccinations in the 2009-2010 and 2010-2011 seasons.

International collaboration to assess the risk of Guillain Barré Syndrome following Influenza A (H1N1) 2009 monovalent vaccines.

BACKGROUND: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination. METHODS: The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach. RESULTS: We found a relative incidence of GBS of 2.42 (95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09 (95% CI 1.28-3.42) using the meta-analytic approach. CONCLUSIONS: This study demonstrates that international collaboration to evaluate serious outcomes using a common protocol is feasible. The significance and consistency of our findings support a conclusion of an association between 2009 H1N1 vaccination and GBS. Given the rarity of the event the relative incidence found does not provide evidence in contradiction to international recommendations for the continued use of influenza vaccines.

Immune response to 2009 H1N1 vaccine in HIV-infected adults in Northern Thailand.

BACKGROUND: In late 2009, the Thai Ministry of Public Health provided two million doses of the monovalent pandemic influenza H1N1 2009 vaccine (Panenza®, Sanofi Pasteur), which was the only vaccine formulation available in Thailand, to persons at risk of more severe manifestations of the disease including HIV infection. Several studies have shown poorer immune responses to the 2009 H1N1 vaccines in HIV-infected individuals. There are limited data in this population in resource-limited countries. RESULTS: At day 28 post-vaccination, seroconversion was found in 32.0% (95%CI 24.5 - 40.2) of the HIV-infected group and 35.0% (95%CI 15.4- 59.2) of the healthy controls (p = 0.79). Seroprotection rate was observed in 33.3% (95%CI 25.8-41.6) and 35.0% (95%CI 15.4-59.2) of the HIV-infected group and the control group, respectively (p = 0.88). Among HIV-infected participants, the strongest factor associated with vaccine response was age 42 y or younger (p = 0.05). METHODS: We evaluated the immunogenicity of a single, 15µg/0.5ml dose of a monovalent, non-adjuvanted 2009 H1N1 vaccine in 150 HIV-infected Thai adults and 20 healthy controls. Immunogenicity was measured by hemagglutination inhibition assay (HI) at baseline and 28 d after vaccination. Seroconversion was defined as 1) pre-vaccination HI titer < 1:10 and post-vaccination HI titer ≥ 1:40, or 2) pre-vaccination HI titer ≥ 1:10 and a minimum of 4-fold rise in post-vaccination HI titer. Seroprotection was defined as a post-vaccination HI titer of ≥ 1:40. CONCLUSIONS: A low seroconversion rate to the 2009 H1N1 vaccine in both study groups, corresponding with data from trials in the region, may suggest that the vaccine used in our study is not very immunogenic. Further studies on different vaccines, dosing, adjuvants, or schedule strategies may be needed to achieve effective immunization in HIV-infected population.

A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1)inactivated monovalent vaccines with different adjuvant systems

We conducted a phase I, multicenter, randomized, double-blind, placebo-controlled, multiarm(10) parallel study involving healthy adults to evaluate the safety and immunogenicity of influenzaA (H1N1) 2009 non-adjuvanted and adjuvanted candidate vaccines. Subjects received two intramuscularinjections of one of the candidate vaccines administered 21 days apart. Antibody responses weremeasured by means of hemagglutination-inhibition assay before and 21 days after each vaccination. Thethree co-primary immunogenicity end points were the proportion of seroprotection >70%, seroconversion40%, and the factor increase in the geometric mean titer 2.5. A total of 266 participants were enrolled into the study. No deaths or serious adverse eventswere reported. The most commonly solicited local and systemic adverse events were injection-site painand headache, respectively. Only three subjects (1.1%) reported severe injection-site pain. Four 2009 influenza A (H1N1) inactivated monovalent candidate vaccines that met the three requirements to evaluateinfluenza protection, after a single dose, were identified: 15 g of hemagglutinin antigen withoutadjuvant; 7.5 g of hemagglutinin antigen with aluminum hydroxide, MPL and squalene; 3.75 g ofhemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 g of hemagglutinin antigen with aluminum hydroxide and squalene.Adjuvant systems can be safely used in influenza vaccines, including the adjuvant monophosphory lipid A (MPL) derived from Bordetella pertussis with squalene and aluminum hydroxide, MPL with aluminum hydroxide, and squalene and aluminum hydroxide.

Preventive behaviors, beliefs, and anxieties in relation to the swine flu outbreak among college students aged 18-24 years.

AIM: The objective of this study was to assess beliefs, misconception, and anxiety in relation to swine flu outbreak and whether perception of the outbreak predicted changes in behavior. SUBJECT AND METHODS: In November 2009, we conducted an Internet-based cross-sectional survey of college students aged 18-24 years in a Midwestern State in the USA. We collected information on swine flu knowledge, perception on immunization safety, perceived efficacy of recommended behavior, changed behavior, and anxiety. RESULTS: Of the 236 respondents, 83.1% had some anxiety about swine flu, 64.8% believed avoiding crowded places was preventive, 33.5% believed the 2009 swine flu vaccine was safe, and 36.9% showed interest in receiving the vaccine. Misconceptions about swine flu contagion via eating cooked pork, water sources, and insect bites were common. Respondents were unaware of transmissions via contaminated objects and droplets. Only 42.6% were satisfied with governmental efforts. Women were more likely to wash hands frequently than men (odds ratio 2.80, p < 0.001). CONCLUSION: There is a gap in swine flu knowledge, minimal risk reduction, increased amount of anxiety, and skepticism about swine flu vaccine safety. These gaps warrant serious attention to inform the public about specific actions regarding swine flu.

Analysis of Hematuria and Proteinuria Caused by Influenza A/H1N1 Vaccine in Our Hospital / 中国药房

OBJECTIVE:To probe into the safety of influenza A/H1N1 vaccine. METHODS:1 200 medical staff who were vaccinated influenza A/H1N1 vaccine on Oct. 27 th of 2009 were followed up on next day. Those cases of severe hematuria and proteinuria were analyzed and reported. RESULTS:A 32 years old woman developed abdominal pain,lumbago,accompanied by frequent urination,urgency of urination and odynuria in 20 hours after vaccinated influenza A/H1N1 vaccine. Routine urine tests showed dark red turbid urine,RBC(+ + +),proteinuria(+ + +). 20 days later,the index of routine urine test returned to normal. CONCLUSION:Hematuria and proteinuria caused by influenza A/H1N1 vaccine shows rare adverse reaction while great importance should be attached to it.