Venovenous extracorporeal membrane oxygenation for COVID-19 and influenza H1N1 associated acute respiratory distress syndrome:A comparative cohort study in China

Background Venovenous extracorporeal membrane oxygenation(VV-ECMO)has been demonstrated to be effective in treating patients with virus-induced acute respiratory distress syndrome(ARDS).However,whether the management of ECMO is different in treating H1N1 influenza and coronavirus disease 2019(COVID-19)-associated ARDS patients remains unknown.Methods This is a retrospective cohort study.We included 12 VV-ECMO-supported COVID-19 patients admitted to The First Affiliated Hospital of Guangzhou Medical University,Guangzhou Eighth People's Hospital,and Wuhan Union Hospital West Campus between January 23 and March 31,2020.We retrospectively included VV-ECMO-supported patients with COVID-19 and H1N1 influenza-associated ARDS.Clinical characteristics,respiratory mechanics including plateau pressure,driving pressure,mechanical power,ventilatory ratio(VR)and lung compliance,and outcomes were compared.Results Data from 25 patients with COVID-19(n=12)and H1N1(n=13)associated ARDS who had received ECMO support were analyzed.COVID-19 patients were older than H1N1 influenza patients(P=0.004).The partial pressure of arterial carbon dioxide(PaCO_(2))and VR before ECMO initiation were significantly higher in COVID-19 patients than in H1N1 influenza patients(P<0.001 and P=0.004,respectively).COVID-19 patients showed increased plateau and driving pressure compared with H1N1 subjects(P=0.013 and P=0.018,respectively).Patients with COVID-19 remained longer on ECMO support than did H1N1 influenza patients(P=0.015).COVID-19 patients who required ECMO support also had fewer intensive care unit and ventilator-free days than H1N1.Conclusions Compared with H1N1 influenza patients,COVID-19 patients were older and presented with increased PaCO_(2) and VR values before ECMO initiation.The differences between ARDS patients with COVID-19 and influenza on VV-ECMO detailed herein could be helpful for obtaining a better understanding of COVID-19 and for better clinical management.

Clinical Predictors for Diagnosing Pandemic (H1N1) 2009 and Seasonal Influenza (H3N2) in Fever Clinics in Beijing,China

Objective Symptomatic predictors of influenza could assess risks and improve decisions about isolation and outpatient treatment. To develop such predictors, we undertook a prospective analysis of pandemic （HIN1） 2009 and seasonal influenza （H3N2） in patients attending fever clinics. Methods From 1 May 2009 to 1 January 2010, all adult patients admitted to fever clinics for suspected influenza, confirmed by real time RT-PCR, were enrolled. Predictors of influenza virus infection were selected with logistic regression models. Measures of sensitivity, specificity, positive and negative likelihood ratios （LRs） were calculated to identify the best predictors. Results The clinical features and routine blood test results of influenza （H1N1） 2009 and seasonal influenza were similar. The positive and negative LRs of current US CDC influenza-like illness （ILl） criteria were modest in predicting influenza infection. Our modified clinic predictors improved the ability of the positive and negative LRs to recognize pandemic （HIN1） 2009 and seasonal influenza. The revised criteria are： fever ~ 38 ~C accompanied by at least one of the following--cough, arthralgia or relative iymphopenia. Conclusion Patients with symptoms and signs that meet the new criteria are likely to have influenza and timely antiviral therapy may be appropriate. In addition, physicians should ascertain if influenza is circulating within the community or if there is a contact history of influenza and combine this information with the newly developed criteria to clinically diagnose influenza.

Novel H1N1 influenza A virus infection in a patient with acute rejection after liver transplantation

BACKGROUND:The 2009 H1N1 influenza A virus was first identified in April 2009 and rapidly evolved into a pandemic. Recipients of solid-organ transplants have a higher risk for severe infection because of immunosuppression.There are limited reports of 2009 H1N1 influenza in liver transplant recipients,especially in China. METHODS:We present a case of a 48-year-old male liver transplant recipient with 2009 H1N1 influenza A virus.He received therapy for acute rejection after transplantation and was confirmed with H1N1 virus infection. RESULTS:The patient was started on oseltamivir(75 mg, orally twice daily)and had a benign hospital course,with defervescence and resolution of symptoms within 72 hours. The follow-up chest radiograph after discharge was normal. CONCLUSIONS:The 2009 H1N1 influenza in this hospitalized transplant recipient was relatively mild,and prolonged viral shedding was not noted.Oseltamivir can be a valid measure in immunocompromised individuals.

Severe Novel Influenza A(H1N1) in Shanghai:Clinical Features, Therapeutic Management and Risk Factors for Mortality

Objective To analyze the clinical features,therapeutic management and risk factors for mortality of patients with severe novel A(H1N1)influenza in Shanghai,China.Methods All patients were diagnosed by influenza A(H1N1)virus mRNA detection.Chest CT scan,routine blood,hepatic function,humoral and cellular immunity,sputum smears,and sputum cultures were performed.Logistic analysis was applied to identify risk factors for mortality.Results Total of 68 patients were enrolled in this study,the primary clinical symptoms including cough(66,97.1%),expectoration(41,60.3%),and polypnea(41,60.3%).Altogether,37(54.4%)and 11(16.2%)patients were infected with bacterial and fungal,respectively.CT scan demonstrated that 67(98.6%)patients had pneumonia.Oxygen therapy,oseltamivir,antibiotic and antifungal drugs were performed in 68(100%),66(97.1%),39(57.4%),and 11(16.2%)patients,respectively.Finally,4 of 68 patients died.Logistic analysis demonstrated that there was a significant correlation between the percentage of neutrophils and mortality before therapy and direct bilirubin content and mortality after therapy,respectively.Conclusions Patients with severe H1N1 influenza were susceptible to bacterial and/or fungal infection.The risk factors for mortality may be associated with pre-therapeutic neutrophil percentage and post-therapeutic direct bilirubin content.

Knowledge and preventive measures practiced by junior high school students from Mexico City regarding influenza A (H1N1)

Background: Influenza A (H1N1) is the most recent pandemic disease that has affected the human population. Objective: To evaluate knowledge and preventive measures related with this disease one year after the epidemic of Mexico- that took place in 2009. Material and methods: An epidemiologic survey regarding influenza A (H1N1) was conducted in June 2010 among 2541 students from the second grade of all public high schools in a borough in Mexico City. The questionnaire included items on the knowledge of the disease and practice of preventive measures. Results: Most students obtained the information from television, half of them from parents and only one fifth from teachers;72% of the participants had a favorable knowledge about the disease and the measures to avoid being infected. However, only 37% practiced such preventive measures. Conclusion: Knowledge has a positive influence on practices towards health. Parents and teachers have an important role in health education, thus efforts should be directed to involve them more intensely in health education.

Effect of Aluminum Hydroxide Adjuvant on the Immunogenicity of the 2009 Pandemic Influenza A/H1N1 Vaccine:Multi-level Modeling of Data with Repeated Measures

Objective To evaluate the effect of the aluminum hydroxide （Al-OH） adjuvant on the 2009 pandemic influenza A/H1N1 （pH1N1） vaccine. Methods In a multicenter, double-blind, randomized, placebo-controlled trial, participants received two doses of split-virion formulation containing 15 ug hemagglutinin antigen, with or without aluminum hydroxide （N-OH）. We classified the participants into six age categories （〉61 years, 41-60 years, 19-40 years, 13-18 years, 8-12 years, and 3-7 years） and obtained four blood samples from each participant on days 0, 21, 35, and 42 following the first dose of immunization. We assessed vaccine immunogenicity by measuring the geometric mean titer （GMT） of hemagglutination inhibiting antibody. We used a two-level model to evaluate the fixed effect of aluminum Al-OH and other factors, accounting for repeated measures. Results The predictions of repeated measurement on GMTs of formulations with or without Al-OH, were 80.35 and 112.72, respectively. Al-OH significantly reduced immunogenicity after controlling for time post immunization, age-group and gender. Conclusion The Al-OH adjuvant does not increase but actually reduces the immunogenicity of the split-virion pH1N1 vaccine.

In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1

This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1.Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures.The docking result showed that AD3BF2 D ligand（N-[（1S,6R）-5-amino-5-{[（2R,3S,4S）-3,4-dihydroxy-4-（hydroxymethyl） tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-1-yl]acetamide-3-（1-ethylpropoxy）-1-cyclohexene-1-carboxylate） had better binding energy values than standard oseltamivir.AD3BF2 D had several interactions,including hydrogen bonds,with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation.The results showed that AD3BF2 D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.

Traditional Chinese medicine as monotherapy or combined with oseltamivir in the treatment of H1N1 influenza:a systematic review and meta-analysis

Objective This study aimed to assess the efficacy and safety of traditional Chinese medicine,alone or in combination with oseltamivir,in patients with H1N1 Influenza.Methods In the present study,we searched the Cochrane Central Register of Controlled Trials,PUBMED,EMBASE,Chinese Biomedical Literature Database,China Science and Technology Journal Database,China National Knowledge Infrastructure Database,and WanFang Data for studies published in or before February 8,2022.Data were extracted and checked by two investigators.Review Manager 5.4 and STATA statistical software 16.0 were used for the data analysis.Results We identified 22 individual studies reporting data from 2292 individuals with H1N1 influenza.Compared with oseltamivir,the fever clearance duration[MD=-3.99,95%CI(-6.89,-1.09)]and sore throat relief time[MD=-5.39,95%CI(-10.19,-0.59)]in the intervention group of traditional Chinese medicine monotherapy or combined with oseltamivir were shorter.Maxingshigan was the primary component of Lianhuaqingwen.The subgroup analyses indicated that Maxingshigan shortened fever clearance time[MD=-3.23,95%CI(-5.60,-0.85)],and also had certain advantages in relieving sore throat[RR=-4.55,95%CI(-10.04,0.95)].However,as for the effective rate,fever duration,cough disappearance time,hospital length of stay,clinical symptoms time as well as viral shedding duration,there were no significant differences between the two groups.Besides,no serious adverse effects were reported in the included studies.Conclusion Although we couldn’t get a definitive conclusion due to the small sample sizes and high risk of bias in the included studies,most traditional Chinese medicine showed similar effects to oseltamivir in treating H1N1 influenza.Some were showed to have a statistically significant shorter time of fever clearance and sore throat remission when they were used alone or in combination with oseltamivir and were well-tolerated treatment,such as Maxingshigan.

Morphofunctional Characteristics of Pulmonary Surfactant System and Its Effect on Immune Cells in Influenza A (H1N1) Pathogenesis

There is an annual increase of influenza-related SARI cases in winter months. Despite the high relevance of this problem, influenza pathogenesis and the role of surfactant system and its SP-A (surfactant protein A) enzyme in antiviral defense remain poorly understood. SP-A activates macrophage M1 polarization and triggers an antiviral response due to the activation of T-cells and dendritic cells. Therefore, surfactant system is an important element of infection protection and a promising therapeutic target.

Seroprevalence study of infection with influenza A(H1N1)pdm09 virus in San Felipe Town, Chile

Objective: To know the natural history of the first wave of pandemic influenza A(H1N1)pdm09 in the Southern hemisphere, through the detection of antibodies against influenza A(H1N1)pdm09 in a selected community, to estimate the population attack rate and its variations, the consultation rates, hospitallization and mortality rates. Methodology: A representative random sample of the population of a commune in Chile (San Felipe) was interviewed and taken blood samples between January and March 2010. A study against the antibodies of the influenza A(H1N1) pdm09 virus was conducted, by the technique of the Hemaglutination Inhibition (HAI) according to standardized methodology. Subjects with antibody titers ≥1:40 were considered positive. Results: 13.5% of the population of San Felipe had antibodies against influenza A(H1N1)pdm09;this percentage reached 30% of the population between 0 and 18 years and 6.1% among those over 19 years. The age variable was the only factor that evidenced significant differences in the prevalence of antibodies. There were no significant differences related to gender, vaccination history against seasonal inluenza, or comorbidity. 51% of people with positive serology showed IN-FLUENZA-LIKE SYMPTOMS. Conclusions: A relevant percentage of subclinical disease was detected in the first pandemic wave in Chile and the proportion of people with SARI and deaths was small. Data from epidemiological surveillance were useful to estimate the trend of TSI but not its magnitude.

A Review on 2009 Influenza A Virus

[Objective] The paper was to introduce the research progress of 2009 influenza A virus. [Method] 2009 influenza A virus was introduced from the aspects of classification and host, virology, molecular characteristics and vaccine. [Result] A novel influenza A/H1N1 virus emerged in early April 2009 quickly spread worldwide through human-to-human transmission. The virus contained a group of novel gene segments, the nearest known precursor was the virus found in swine. The virus appeared to retain the potential to infect swine again and thus continued reassort with swine viruses. All registered 2009 influenza A vaccines were tested for safety and immunogenicity in clinical trials on human volunteers, and all vaccines were found to be safe, single dose of vaccine could cause protective antibody responses. [Conclusion] The paper provided basis for further study on 2009 influenza A virus.

Immunogenic and Protective Properties of the First Kazakhstan Vaccine against Pandemic Influenza А(Н1N1) pdm09 in Ferrets

This paper presents the results of a pre-clinical study of the immunogenicity and efficacy of an egg-derived, inactivated, whole-virion adjuvanted vaccine （Refluvac） on ferret models. For this purpose, groups of eight ferrets （6 to 7 months old） were injected with 0.5 mL of vaccine specimens containing 3.75, 7.5 or 15.0 μg of virus hemagglutinin. Administration was intramuscular and given either as a single dose or as two doses 14 days apart. All vaccine specimens manifested immunogenicity in ferrets for single （HI titer, from 51 ± 7 to 160 ± 23） and double （HI titer, from 697± 120 to 829 ± 117） administrations. To assess the protective effects of the vaccine, ferrets from the vaccinated and control groups were infected intranasally with pandemic virus A/California/7/09 （H1N1） pdm09 at a dose of 106 106/0.5 mL. Fourteen days post-infection, the ferrets inoculated with single or double vaccines containing 3.75, 7.5 or 15.0 ~g of hemagglutinin per dose showed no signs of influenza infection, weight loss, or body temperature rise, and no premature deaths occurred. The number of vaccinated ferrets shedding the virus via the upper airway, as well as the amount of virus shed after infection, was significantly reduced in comparison with animals from the control group. Based on our results, we suggest that a single vaccination at a dose of 3.75 or 7.5 μg hemagglutinin be used for Phase I clinical trials.

Close Relationship between the 2009 H1N1 Virus and South Dakota AIV Strains

Although previous publications suggest the 2009 pandemic influenza A (H1N1) virus was reassorted from swine viruses of North America and Eurasia,the immediate ancestry still remains elusive due to the big evolutionary distance between the 2009 H1N1 virus and the previously isolated strains. Since the unveiling of the 2009 H1N1 influenza,great deal of interest has been drawn to influenza,consequently a large number of influenza virus sequences have been deposited into the public sequence databases. Blast analysis demonstrated that the recently submitted 2007 South Dakota avian influenza virus strains and other North American avian strains contained genetic segments very closely related to the 2009 H1N1 virus,which suggests these avian influenza viruses are very close relatives of the 2009 H1N1 virus. Phylogenetic analyses also indicate that the 2009 H1N1 viruses are associated with both avian and swine influenza viruses circulating in North America. Since the migrating wild birds are preferable to pigs as the carrier to spread the influenza viruses across vast distances,it is very likely that birds played an important role in the inter-continental evolution of the 2009 H1N1 virus. It is essential to understand the evolutionary route of the emerging influenza virus in order to find a way to prevent further emerging cases. This study suggests the close relationship between 2009 pandemic virus and the North America avian viruses and underscores enhanced surveillance of influenza in birds for understanding the evolution of the 2009 pandemic influenza.

Natural herbal medicine Lianhuaqingwen capsule anti-influenza A （H1N1） trial： a randomized, double blind, positive controlled clinical trial

Background The 2009 influenza A （H1N1） virus infection is associated with the high risk of severe complications and is spreading more rapidly throughout the world than other reported seasonal influenzas. This study aimed to evaluate the efficacy and safety of the nature herbal medicine Lianhuaqingwen capsule （LHC） in patients infected with influenza A （H1N1） virus. Methods A total of 244 patients aged 16-65 years confirmed with influenza A （H1N1） virus infection by the real time RT-PCR were randomized to one of two treatment groups of 122 patients each. Each group assigned to receive either LHC or Oseltamivir for five days and observation for seven days. The patients were enrolled within 36 hours of illness onset if they had an axillary temperature of ≥37.4℃ and with at least one of the following symptoms： nasal obstruction, runny nose, cough, sore throat, fatigue, headache, myalgia, chills and sweating. The primary end point was the duration of illness. Results Of 244 patients, 240 （98.36%） patients with a median age 21 years completed the study between October 24, 2009 and November 23, 2009. There were no significant overall differences between LHC treated and Oseltamivir treated patients in the median duration of illness （LHC 69 hours vs. Oseltamivir 85 hours P 〉0.05） or the median duration of viral shedding （LHC 103 hours vs. Oseltamivir 96 hours, P 〉0.05）. However, it was worthwhile to note that LHC significantly reduced the severity of illness and the duration of symptoms including fever, cough, sore throat, and fatigue （P〈0.05）. Both study medications were well tolerated. No drug related serious adverse events occurred during the study. Conclusions Compared with Oseltamivir, LHC achieved a similar therapeutic effectiveness reduction of the duration of illness and duration of viral shedding. Therefore, LHC might be an alternative therapeutic measure for influenza A （H1N1） virus infections.

Reduning plus ribavirin display synergistic activity against severe pneumonia induced by H1N1 influenza A virus in mice

OBJECTIVE:To investigate synergistic effect of Reduning(RDN)injection plus ribavirin against severe pneumonia induced by H1 N1 influenza A virus in mice.METHODS:We established a mouse model of severe pneumonia induced by influenza A virus by infecting Balb/c mice with CA07 virus.We randomly assigned the infected mice into four groups,and treated them with normal saline(NS group),RDN(injection,86.6 mg/kg),ribavirin(injection,66.6 mg/kg)or double Ribavirin plus RDN group,the same dosage as used in the single treatments)for 5 d.Lung index and lung pathology were recorded or calculated in terms of the curative effective.Cytokines,NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome related protein including caspase-associated recruitment domain(CARD)domain Apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),caspase-1 and NOD-like receptor family,pyrin domain containing 3(NLRP3),and reactive oxygen species were simultaneously investigated.RESULTS:RDN plus ribavirin treatment,not RDN or ribavirin alone,provided a significant survival benefit to the influenza A virus-infected mice.The combination treatment protected the mice against severe influenza infection by attenuating the severe lung injury.The combined treatment also reduced the viral titers in mouse lungs and lung index,downregulated their immunocytokine levels,including IL-1βand IL-18,and down regulated the NLRP3,especially the transcription and translation of caspase-1.Meanwhile NS group had significantly higher reactive oxygen species(ROS)expression which could was dramatically reduced by the treatment of RDN plus ribavirin.CONCLUSION:Our study showed that RDN combined with ribavirin could protect the mice,and reduce the lung immunopathologic damage caused by severe influenza pneumonia.The mechanism could be that it reduced ROS produce and inhibited NLRP3 inflammasome activation so that mainly lower the downstream inflammatory cytokines IL-1βand IL-18.

Hospitalized patients with novel influenza A （H1N1） virus infection： Shanghai, June-July 2009

Background From late May 2009, sporadic imported cases of novel influenza A （HIN1） were continuously confirmed in Shanghai, but there were few reports on its clinical presentation in China. The aim of the study was to investigate the demographic and clinical features of the laboratory-confirmed cases and the treatment with oseltamivir. Method We performed a retrospective study in the Shanghai Public Health Clinical Center （SHAPHC）, reviewing the medical records of the laboratory-confirmed patients derived from June 10 to July 20, 2009. Results A total of 156 cases were enrolled, of whom 152 had a history of recent travel. The mean age was 22.6 years and 89 cases （57.1%） were males. The most common symptoms were fever, cough, and sore throat, with children more likely to run a temperature above 38.5℃ than adults. The mean leucocyte count was 5.4×10^9/L, the mean neutrophil count 3.2×10^9/L and the mean lymphocyte count 1.4×10^9/L. Other findings included a normal range or elevated level of C-reactive protein （CRP） and glutamic-pyruvic transaminase and a normal or decreased level of prealbumin; the levels of prealbumin and CRP were significantly lower in the children than in the adults. Fifty-two patients had abnormal chest CT results, with small unilateral or bilateral pulmonary infiltrates, axillary and mediastinal lymphadenopathy and local pleural thickening, while no cases showed symptoms of hypoxia. All the patients received oseltamivir and recovered without complications, but the duration of fever and virus shedding were significantly longer in the children than in the adults. Conclusions Travel-related circulation may be an important reason for the H1N1 epidemic in the non-epidemic areas, and the virus caused mild respiratory symptoms. The infection in children was more severe in terms of prealbumin levels, temperature, the duration of fever and virus shedding. Oseltamivir was effective for H1N1, but more effective in the adults than in the children.

Influenza A pandemic （H1N1） 2009 virus infection

The clinical spectrum of the 2009 pandemic influenza A （H1N1） infection ranged from self-limited mild illness to progressive pneumonia, or even a fatal outcome. We summarize the clinical manifestations, risk factors for severe and fatal cases, pathologic findings and treatment of this disease in this paper based on current reports from different regions of the world.

Clinical features of initial cases of 2009 pandemic influenza A （H1N1） in Macao, China

Background The first case of pandemic influenza A （H1N1） virus infection in Macao Special Administrative Region （SAR） of the People＇s Republic of China was documented on June 18, 2009. Subsequently, persons with suspected infection or of contact with suspected cases received screening. All the confirmed cases were hospitalized and treated with oseltamivir. Their clinical features were observed. This may help for better management for later patients and be of benefit to the government of Macao SAR to adjust its strategy to combat the pandemic influenza A （H1N1） virus infection more efficiently. Methods From June to July 2009, the initial 72 cases of influenza A （H1N1） in Macao were hospitalized in Common Hospital Centre S. Januario （CHCSJ）. The infection was confirmed by real-time reverse-transcriptase polymerase chain reaction （RT-PCR）. The clinical features of the disease were closely observed and documented. Oseltamivir was given to all patients within 48 hours after the onset of disease and maintained for 5 days. Results The mean age of the 72 patients was 21 years old. Forty of them were men and 32 were women. The median incubation of the virus was 2 days （1 to 7 days）. The most common symptoms were fever （97.2%） and cough （77.8%）. The rate of gastrointestinal symptoms including nausea, vomiting, and diarrhea was 2.8%. Fever typically lasted for 3 days （1 to 9 days）. The median time from the onset to positive results of real-time RT-PCR was 6 days （3 to 13 days）. After treatment with oseltamivir, most patients became afebrile within 48 hours. Only one aged patient with a history of glaucoma and hypothyroidism was found to have lung infiltration on chest X-ray. Conclusions The initial cases of pandemic influenza A （H1N1） virus infection in Macao SAR showed that most of the infected persons had a mild course. The virus could be detected by real-time RT-PCR within a median of 6 days from the onset. Oseltamivir was effective.

Influence of extreme weather and meteorological anomalies on outbreaks of influenza A (H1N1)

Biological experiments and epidemiological evidence indicate that variations in environment have important effect on the occurrence and transmission of epidemic influenza.It is therefore important to understand the characteristic patterns of transmission for prevention of disease and reduction of disease burden.Based on case records,we analyzed the environmental characteristics including climate variables in Changsha,and then constructed a meteorological anomaly susceptive-infective-removal (SIR) model on the basis of the results of influenza A (H1N1) transmission.The results showed that the outbreak of influenza A (H1N1) in Changsha showed significant correlation with meteorological conditions;the spread of influenza was sensitive to meteorological anomalies,and that the outbreak of influenza A (H1N1) in Changsha was influenced by a combination of absolute humidity anomalous weather conditions,contact rates of the influenza patients and changes in population movements.These findings will provide helpful information regarding prevention strategies under different conditions,a fresh understanding of the emergence and re-emergence of influenza outbreaks,and a new perspective on the transmission dynamics of influenza.

Response of BALB/c mice to a monovalent influenza A （H1N1） 2009 split vaccine

The novel influenza A （H1N1） 2009 virus has emerged to cause the first pandemic of the twenty-first century. Disease outbreaks caused by the influenza A （H 1N 1） virus have prompted concerns about the potential for a pandemic and have driven the development of vaccines against this subtype of influenza A. In this study, we developed a monovalent influenza A （H 1N 1） split vaccine and evaluated its effects in BALB/c mice. Mice were immunized subcutaneously with 2 doses of the vaccine containing hemagglutinin （HA） alone or HA plus an aluminum hydroxide （AI（OH）3） adjuvant. Immunization with varying doses of HA （3.75, 7.5, 15, 30, 45 or 60μg） was performed to induce the production of neutralizing antibodies. The vaccine elicited strong hemagglutination inhibition （HI） and microneutralization, and addition of the adjuvant augmented the antibody response. A preliminary safety evaluation showed that the vaccine was not toxic at large doses （0.5 ml containing 60 μg HA＋600 μg AI（OH）3 or 60 μg HA）. Moreover, the vaccine was found to be safe at a dose of 120 μg HA＋ 1200 μg AI（OH）3 or 120 μg HA in 1.0 ml in rats. In conclusion; the present study provides support for the clinical evaluation of influenza A （H1N1） vaccination as a public health intervention to mitigate a possible pandemic. Additionally, our findings support the further evaluation of the vaccine used in this study in primates or humans.