Rudenko Larisa, Kiseleva Irina, Naykhin Anatoly N, Erofeeva Marianna, Stukova Marina, Donina Svetlana, Petukhova Galina, Pisareva Maria, Krivitskaya Vera, Grudinin Michael, Buzitskaya Zhanna, Isakova-Sivak Irina, Kuznetsova Svetlana, Larionova Natalie, Desheva Julia, Dubrovina Irina, Nikiforova Alexandra, Victor John C, Neuzil Kathy, Flores Jorge, Tsvetnitsky Vadim, Kiselev Oleg
Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
Department of Epidemiology and Prophylaxis, Institute of Influenza, Saint Petersburg, Russia.
PLoS One. 2014 Feb 12;9(2):e87962. doi: 10.1371/journal.pone.0087962. eCollection 2014.
Live attenuated influenza vaccines (LAIVs) are being developed to protect humans against future epidemics and pandemics. This study describes the results of a double-blinded randomized placebo-controlled phase I clinical trial of cold-adapted and temperature sensitive H7N3 live attenuated influenza vaccine candidate in healthy seronegative adults.
The goal of the study was to evaluate the safety, tolerability, immunogenicity and potential shedding and transmission of H7N3 LAIV against H7 avian influenza virus of pandemic potential.
Two doses of H7N3 LAIV or placebo were administered to 40 randomly divided subjects (30 received vaccine and 10 placebo). The presence of influenza A virus RNA in nasal swabs was detected in 60.0% and 51.7% of subjects after the first and second vaccination, respectively. In addition, vaccine virus was not detected among placebo recipients demonstrating the absence of person-to-person transmission. The H7N3 live attenuated influenza vaccine demonstrated a good safety profile and was well tolerated. The two-dose immunization resulted in measurable serum and local antibody production and in generation of antigen-specific CD4⁺ and CD8⁺ memory T cells. Composite analysis of the immune response which included hemagglutinin inhibition assay, microneutralization tests, and measures of IgG and IgA and virus-specific T cells showed that the majority (86.2%) of vaccine recipients developed serum and/or local antibodies responses and generated CD4⁺ and CD8⁺ memory T cells.
The H7N3 LAIV was safe and well tolerated, immunogenic in healthy seronegative adults and elicited production of antibodies broadly reactive against the newly emerged H7N9 avian influenza virus.
ClinicalTrials.gov NCT01511419.
正在研发减毒活流感疫苗（LAIV）以保护人类抵御未来的流感流行和大流行。本研究描述了一种对健康血清阴性成年人进行的冷适应和温度敏感H7N3减毒活流感候选疫苗的双盲随机安慰剂对照I期临床试验结果。
本研究的目的是评估H7N3 LAIV针对具有大流行潜力的H7禽流感病毒的安全性、耐受性、免疫原性以及潜在的病毒脱落和传播情况。
将两剂H7N3 LAIV或安慰剂给予40名随机分组的受试者（30名接受疫苗，10名接受安慰剂）。首次和第二次接种后，分别在60.0%和51.7%的受试者鼻拭子中检测到甲型流感病毒RNA。此外，在安慰剂接受者中未检测到疫苗病毒，表明不存在人传人现象。H7N3减毒活流感疫苗显示出良好的安全性，耐受性良好。两剂免疫导致可测量的血清和局部抗体产生，并产生抗原特异性CD4⁺和CD8⁺记忆T细胞。对免疫反应的综合分析包括血凝抑制试验、微量中和试验以及IgG和IgA及病毒特异性T细胞的检测，结果显示大多数（86.2%）疫苗接种者产生了血清和/或局部抗体反应，并产生了CD4⁺和CD8⁺记忆T细胞。
H7N3 LAIV安全且耐受性良好，在健康血清阴性成年人中具有免疫原性，并引发了对新出现的H7N9禽流感病毒具有广泛反应性的抗体产生。
ClinicalTrials.gov NCT01511419。
