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    Home > Active Ingredient News > Infection > NEJM: Cell culture-based quadrivalent influenza vaccine has a higher protective effect on children, expert comments

    NEJM: Cell culture-based quadrivalent influenza vaccine has a higher protective effect on children, expert comments

    • Last Update: 2021-11-05
    • Source: Internet
    • Author: User
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    The annual seasonal influenza epidemic can cause 3 million to 5 million severe cases and 290,000 to 650,000 respiratory disease-related deaths worldwide
    .

    In particular, this year's global COVID-19 pandemic is still continuing, and there may be a superimposed epidemic of COVID-19 and influenza and other respiratory infectious diseases this winter and next spring
    .

    Influenza vaccination is the most effective way to prevent influenza, but flu vaccines based on traditional chicken embryo culture have insufficient problems, such as immunogenic mutations and limited production capacity
    .

    Influenza vaccine based on cell culture can overcome these shortcomings
    .

     On October 14, 2021, the New England Journal of Medicine (NEJM) published a randomized controlled trial on the preventive efficacy of a quadrivalent influenza vaccine made by cell culture technology in children.
    The results show that whether or not they have been vaccinated before Influenza vaccine, the quadrivalent influenza vaccine has a protective effect against influenza in healthy children and adolescents
    .

    "NEJM Frontiers of Medicine" invites the team of Professor Luo Zhengxiu from the Children's Hospital of Chongqing Medical University to comment on this research in depth
    .

     To read the full text translation, please visit the official website and APP of "NEJM Medical Frontier" or click on the picture of the WeChat applet
    .

    Zhang Qian, Luo Zhengxiu* Department of Respiratory Diseases, Children’s Hospital of Chongqing Medical University; National Research Center for Child Health and Disease Clinical Medicine; Key Laboratory of Child Developmental Disease Research of Ministry of Education; Chongqing Key Laboratory of Child Infection and Immunity* Corresponding author Influenza is a common respiratory tract in children Infectious diseases bring a heavy burden to medical care
    .

    Although the results of randomized controlled trials show that influenza vaccination can prevent influenza [1], the actual protective effect of influenza vaccine is not good [2]
    .

    Because vaccine strains are prone to gene mutations when they are passaged in chicken embryos [3], the protective efficacy of influenza vaccines produced by chicken embryo culture may be affected
    .

    Using cell culture to produce influenza vaccines can reduce the risk of gene mutations and shorten the vaccine production cycle.
    When new influenza viruses appear, corresponding vaccines can be quickly produced [4,5]
    .

     Current studies have found that the tetravalent inactivated influenza vaccine (IIV4c) based on cell culture has better immune response and safety in children [6], but the protective efficacy of IIV4c in children is still unclear
    .

    On October 14, 2021, the team of Professor Jonathan Edelman of the Murdoch Children’s Research Institute in Melbourne published the results of a global multicenter randomized controlled trial in the New England Journal of Medicine (NEJM) to explore the protective effect of IIV4c on children[ 7]
    .

     The study was a randomized study of phases 3-4, blinded to observers, and stratified.
    It included 4,514 healthy children and adolescents from 2 to 18 years old (average age of 8.
    8±4.
    1 years) from eight countries, and compared IIV4c with The protective efficacy, immunogenicity and safety of non-influenza vaccines (epidemic cerebrospinal meningitis vaccine [A, C, Y, W135 group conjugate vaccine]), follow-up time of at least 180 days
    .

    All study subjects received 1 dose of trial vaccine
    .

    Children aged 2-9 years in the IIV4c group who had not received influenza vaccine received the second dose of vaccine on the 29th day, and the control group was injected with the same amount of normal saline
    .

    The main outcome indicator is that from 14 days after the last vaccination to the end of the flu season, the research subjects first had flu confirmed by testing (considering the results of RT-PCR and virus culture)
    .

    The test uses Cox regression model to evaluate the protective efficacy of IIV4c
    .

     The overall protective efficacy of IIV4c against influenza in the study population was 54.
    6% (95% CI, 45.
    7%~62.
    1%), and the protective efficacy against influenza A H1N1 was 80.
    7% (95% CI, 69.
    2%~87.
    9%), against influenza A The protective effect of influenza H3N2 was 42.
    1% (95% CI, 20.
    3%~57.
    9%), and the protective effect of influenza B was 47.
    6% (95% CI, 31.
    4%~60.
    0%) (see Table 1 for details)
    .

    IIV4c showed consistent protective efficacy among healthy children and adolescents of different ages, genders, races, and flu vaccination history (see Figure 1 for details)
    .

      Table 1.
    The absolute efficacy of influenza and vaccines confirmed by RT-PCR or virus culture [7] Figure 1.
    The absolute efficacy of laboratory-confirmed influenza and vaccines [7] After vaccination with IIV4c, the subjects all produced neutralization against influenza viruses Antibodies, the geometric mean titer of neutralizing antibodies against H1N1 increased from 283.
    5 to 380.
    7, the geometric mean titer of neutralizing antibodies against H3N2 increased from 67.
    6 to 168.
    7, and the geometric mean titer of neutralizing antibodies against influenza B virus Victoria line increased from 45.
    3 It rose to 66.
    8, and the geometric mean titer of the neutralizing antibody of the Yamagata strain of influenza B virus rose from 52.
    8 to 108.
    5
    .

    The control group did not produce influenza virus neutralizing antibodies
    .

     Within 6 hours to 7 days after vaccination, the incidence of adverse events in the IIV4c group and the control group were 51.
    4% and 48.
    6%, respectively.
    The local and systemic adverse events reported by the two groups were similar
    .

    The most reported adverse reactions were flu-like symptoms, and the incidence of new chronic diseases in both groups was less than 1%
    .

     Recently, major domestic and foreign institutions have updated their recommendations for childhood influenza vaccination
    .

    The Chinese Center for Disease Control and Prevention and the Respiratory Group of the Pediatrics Branch of the Chinese Medical Association recommend that IIV4 can be used for vaccination for people ≥ 6 months old, and 6 to 23 months old and 2 to 5 years old are priority vaccination groups [8,9]
    .

    However, the type of evidence cited is case-control studies and guidelines, rather than high-quality randomized controlled trials or systematic reviews
    .

    The American Academy of Pediatrics also recommends IIV4 vaccination for infants and children over 6 months of age [10].
    Although the evidence cited includes a randomized controlled trial, the randomized controlled trial only explored the immunogenicity and safety of IIV4 and did not study its protection.
    Effectiveness [11]
    .

    Other randomized controlled trials targeting IIV4 also have the problem of not exploring the protective efficacy of IIV4, and these influenza vaccines are based on chicken embryo culture rather than cell culture [12,13]
    .

     This randomized controlled trial explored the protective effect of IIV4c based on cell culture for the first time.
    The method is rigorous, and it provides high-quality evidence-based medicine evidence for IIV4c's recommendations in guidelines and the application of IIV4c in clinical practice
    .

     Although the study is a global multi-center, randomized controlled trial with a large sample size, it still needs further improvement in the following aspects
    .

     First, the study did not select other types of influenza vaccines as controls, and it was impossible to determine whether the cell-cultured influenza vaccines had a stronger protective effect on children than the traditional chicken embryo-cultured influenza vaccines
    .

    Therefore, it is still necessary to carry out high-quality randomized controlled trials or real-world studies in children to compare the protective efficacy or effects of different influenza vaccines
    .

     Second, the study did not include Chinese children.
    Therefore, the protective efficacy, immunogenicity, and safety of the influenza vaccine in Chinese children are still unclear, and it is necessary to be cautious in its promotion in Chinese children
    .

    Encourage future research to include Chinese children, produce Chinese data, and provide Chinese evidence to the world
    .

     Third, the study did not evaluate the cost-effectiveness and cost-effectiveness of IIV4c
    .

    China has a large number of children who need to be vaccinated against influenza.
    If the vaccine has a complicated production process, high research and development costs, and high transportation and storage costs, it may limit its use and promotion in populations in China or underdeveloped areas
    .

    Encourage future research to evaluate the cost-effectiveness and cost-effectiveness of vaccines
    .

     The study found that regardless of previous influenza vaccination, IIV4c has protective effects on healthy children and adolescents, and no serious adverse reactions related to IIV4c were found.
    The study provides high-quality medical evidence for IIV4c to prevent influenza in children
    .

    However, it should be noted that the study was not included in the Chinese children population, and it was not compared with other influenza vaccines.
    It is not clear whether its protective efficacy, safety and cost-effectiveness are better.
    Therefore, the evidence of this study was transformed in Chinese children.
    , It is necessary to carefully evaluate the restricted indicators and use IIV4c reasonably to prevent side effects and adverse events
    .

    References 1.
    Claeys C, Zaman K, Dbaibo G, et al.
    Prevention of vaccine-matched and mismatched influenza in children aged 6-35 months: a multinational randomised trial acrossfive influenza seasons.
    Lancet Child Adolesc Health 2018;2:338-49.
    2 .
    Belongia EA, Simpson MD, King JP, et al.
    Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis oftest-negative design studies.
    Lancet Infect Dis 2016;16:942-51.
    3.
    Barr IG, Donis RO, Katz JM, et al.
    Cell culture-derived influenza vaccines in thesevere 2017-2018 epidemic season: a step towards improved influenza vaccineeffectiveness.
    NPJ Vaccines 2018;3:44.
    4.
    Manini I, Trombetta CM, Lazzeri G, et al.
    Egg-independent influenzavaccines and vaccine candidates.
    Vaccines (Basel) 2017;5:18.
    5.
    Carrat F, Flahault A.
    Influenza vaccine: the challenge of antigenic drift.
    Vaccine 2007;25:6852-62.
    6.
    Hartvickson R, Cruz M, Ervin J, et al.
    Non-inferiority of mammalian cell derivedquadrivalent subunit influenza virus vaccines compared to trivalent subunitinfluenza virus vaccines in healthy children: a phase III randomized,multicenter, double-blind clinical trial.
    Int J Infect Dis2015;41:65-72.
    7.
    Nolan T, Fortanier AC, Leav B, et al.
    Efficacy of a Cell-culture derived quadrivalent Influenza vaccine in children.
    N Engl J Med 2021;385:1485-95.
    8.
    National Respiratory Disease Clinic Medical Research Center, Respiratory Group of Pediatrics Branch of Chinese Medical Association.
    Expert consensus on diagnosis and treatment of children with influenza (2020 edition).
    Chinese Journal of Practical Pediatrics 2020;35:1281-8.
    9.
    National Immunization Program Technical Working Group Influenza Vaccine Working Group.
    Technical Guidelines for Influenza Vaccination in China (2020-2021).
    Chinese Journal of Preventive Medicine 2020:1035-59.
    10.
    COMMITTEE ON INFECTIOUS DISEASES.
    Recommendations for prevention and control of influenza in children, 2021-2022.
    Pediatrics 2021September 7 DOI:10.
    1542/peds.
    2021-053745( Epub ahead of print).
    11.
    Robertson CA, Mercer M, Selmani A, Klein NP,Jeanfreau R, Greenberg DP.
    Safety and immunogenicity of a full-dose, split-virion,inactivated, quadrivalent influenza vaccine in healthy children 6-35 months of age:a randomized controlled clinical trial.
    Pediatr Infect Dis J 2019;38:323- 8.
    12.
    Claeys C, Drame M, García-Sicilia J, et al.
    Assessment of an optimized manufacturing process for inactivated quadrivalentinfluenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults.
    BMC Infect Dis 2018; 18:186.
    13.
    Liu Shuzhen, Meng Li, Xi Peipei, et al.
    Safety and immunogenicity evaluation of the quadrivalent influenza virus split vaccine.
    Preventive Medicine 2020;327:17-21.
    Author introduction Luo Zhengxiu, chief physician, professor, affiliated to Chongqing Medical University Director of Respiratory Department of Children's Hospital, PhD supervisorGarcía-Sicilia J, et al.
    Assessment of an optimized manufacturing process for inactivated quadrivalentinfluenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults.
    BMC Infect Dis 2018;18:186.
    13.
    Liu Shuzhen, Meng Li , Xi Peipei, et al.
    Evaluation of the safety and immunogenicity of the quadrivalent influenza virus split vaccine.
    Preventive Medicine 2020;327:17-21.
    Author introduction Luo Zhengxiu, chief physician, professor, director of the Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, PhD student tutorGarcía-Sicilia J, et al.
    Assessment of an optimized manufacturing process for inactivated quadrivalentinfluenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults.
    BMC Infect Dis 2018;18:186.
    13.
    Liu Shuzhen, Meng Li , Xi Peipei, et al.
    Evaluation of the safety and immunogenicity of the quadrivalent influenza virus split vaccine.
    Preventive Medicine 2020;327:17-21.
    Author introduction Luo Zhengxiu, chief physician, professor, director of the Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, PhD student tutor
    .

    He has been engaged in pediatric clinical work for 25 years, and is good at clinical diagnosis and treatment of respiratory tract infections and allergic diseases in children.
    He is the first to carry out hypertonic saline treatment for bronchiolitis in China.
    The research results are cited in the US 2014 Management Guidelines for bronchiolitis
    .

    Vice Chairman of the Child Allergy Specialty Committee of the China Association for the Advancement of Human Health Science and Technology, Vice Chairman of the Chronic Cough Cooperation Group and Member of the Asthma Cooperation Group of the Pediatric Branch of the Chinese Medical Association, Vice Chairman of the Child Health Specialty Committee of Chongqing Women and Children's Association, Chongqing Children Leader of the Asthma Collaboration Group, Chongqing Elite Innovation Leader Winner
    .

     Copyright information This article was translated, written or commissioned by the "NEJM Frontiers of Medicine" jointly created by the Jiahui Medical Research and Education Group (J-Med) and the "New England Journal of Medicine" (NEJM)
    .

    The Chinese translation of the full text and the included diagrams are exclusively authorized by the NEJM Group
    .

    If you need to reprint, please leave a message or contact nejmqianyan@nejmqianyan.
    cn
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