Belshe R B, Mendelman P M, Treanor J, King J, Gruber W C, Piedra P, Bernstein D I, Hayden F G, Kotloff K, Zangwill K, Iacuzio D, Wolff M
Department of Medicine, Saint Louis University, MO 63110, USA.
N Engl J Med. 1998 May 14;338(20):1405-12. doi: 10.1056/NEJM199805143382002.
Influenzavirus vaccine is used infrequently in healthy children, even though the rates of influenza in this group are high. We conducted a multicenter, double-blind, placebo-controlled trial of a live attenuated, cold-adapted, trivalent influenzavirus vaccine in children 15 to 71 months old.
Two hundred eighty-eight children were assigned to receive one dose of vaccine or placebo given by intranasal spray, and 1314 were assigned to receive two doses approximately 60 days apart. The strains included in the vaccine were antigenically equivalent to those in the inactivated influenzavirus vaccine in use at the time. The subjects were monitored with viral cultures for influenza during the subsequent influenza season. A case of influenza was defined as an illness associated with the isolation of wild-type influenzavirus from respiratory secretions.
The intranasal vaccine was accepted and well tolerated. Among children who were initially seronegative, antibody titers increased by a factor of four in 61 to 96 percent, depending on the influenza strain. Culture-positive influenza was significantly less common in the vaccine group (14 cases among 1070 subjects) than the placebo group (95 cases among 532 subjects). The vaccine efficacy was 93 percent (95 percent confidence interval, 88 to 96 percent) against culture-confirmed influenza. Both the one-dose regimen (89 percent efficacy) and the two-dose regimen (94 percent efficacy) were efficacious, and the vaccine was efficacious against both strains of influenza circulating in 1996-1997, A(H3N2) and B. The vaccinated children had significantly fewer febrile illnesses, including 30 percent fewer episodes of febrile otitis media (95 percent confidence interval, 18 to 45 percent; P<0.001).
A live attenuated, cold-adapted influenzavirus vaccine was safe, immunogenic, and effective against influenza A(H3N2) and B in healthy children.
尽管健康儿童中流感发病率较高，但流感病毒疫苗在这一群体中使用并不频繁。我们对15至71个月大的儿童进行了一项多中心、双盲、安慰剂对照试验，使用的是减毒活、冷适应三价流感病毒疫苗。
288名儿童被分配接受一剂通过鼻内喷雾给予的疫苗或安慰剂，1314名儿童被分配接受两剂，间隔约60天。疫苗中包含的毒株在抗原性上与当时使用的灭活流感病毒疫苗中的毒株相当。在随后的流感季节，通过病毒培养对受试者进行流感监测。流感病例定义为与从呼吸道分泌物中分离出野生型流感病毒相关的疾病。
鼻内疫苗被接受且耐受性良好。在最初血清学阴性的儿童中，根据流感毒株不同，抗体滴度提高四倍的比例在61%至96%之间。疫苗组中培养阳性的流感病例（1070名受试者中有14例）明显少于安慰剂组（532名受试者中有95例）。针对培养确诊的流感，疫苗效力为93%（95%置信区间，88%至96%）。单剂量方案（效力89%）和两剂量方案（效力94%）均有效，该疫苗对1996 - 199年流行的两种流感毒株A(H3N2)和B均有效。接种疫苗儿童的发热性疾病明显减少，包括发热性中耳炎发作减少30%（95%置信区间，18%至45%；P<0.001）。
减毒活、冷适应流感病毒疫苗对健康儿童中的甲型流感病毒A(H3N2)和乙型流感安全、具有免疫原性且有效。
