Hoft Daniel F, Lottenbach Kathleen R, Blazevic Azra, Turan Aldin, Blevins Tamara P, Pacatte Thomas P, Yu Yinyi, Mitchell Michelle C, Hoft Stella G, Belshe Robert B
Division of Infectious Diseases, Allergy & Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA
Division of Infectious Diseases, Allergy & Immunology, Department of Internal Medicine, Saint Louis University, St. Louis, Missouri, USA.
Clin Vaccine Immunol. 2017 Jan 5;24(1). doi: 10.1128/CVI.00414-16. Print 2017 Jan.
Both live attenuated influenza vaccines (LAIV) and inactivated influenza vaccines (IIV) induce protective immunity against influenza. There is evidence that LAIV induces superior protection in children, whereas IIV may induce superior protection in adults. The immune mechanisms responsible for these differences have not been identified. We previously compared LAIV and IIV in young children of 6 to 36 months of age, and we demonstrated that while both induced similar hemagglutination inhibition (HAI) antibody responses, only LAIV induced significant increases in T cell responses. In the present study, 37 healthy adult subjects of 18 to 49 years of age were randomized to receive seasonal influenza vaccination with LAIV or IIV. Influenza virus-specific HAI, T cell, and secretory IgA (sIgA) responses were studied pre- and postvaccination. In contrast to the responses seen in young children, LAIV induced only minimal increases in serum HAI responses in adults, which were significantly lower than the responses induced by IIV. Both LAIV and IIV similarly induced only transient T cell responses to replication-competent whole virus in adults. In contrast, influenza virus-specific sIgA responses were induced more strongly by LAIV than by IIV. Our previous studies suggest that LAIV may be more protective than IIV in young children not previously exposed to influenza virus or influenza vaccines due to increased vaccine-induced T cell and/or sIgA responses. Our current work suggests that in adults with extensive and partially cross-reactive preexisting influenza immunity, LAIV boosting of sIgA responses to hemagglutinin (HA) and non-HA antigenic targets expressed by circulating influenza virus strains may be an important additional mechanism of vaccine-induced immunity.
减毒活流感疫苗(LAIV)和灭活流感疫苗(IIV)均可诱导针对流感的保护性免疫。有证据表明,LAIV在儿童中诱导的保护作用更强,而IIV在成人中可能诱导更强的保护作用。导致这些差异的免疫机制尚未明确。我们之前比较了6至36个月大的幼儿中的LAIV和IIV,结果表明,虽然二者诱导的血凝抑制(HAI)抗体反应相似,但只有LAIV能显著增加T细胞反应。在本研究中,37名18至49岁的健康成人受试者被随机分配接受LAIV或IIV季节性流感疫苗接种。在接种疫苗前后研究了流感病毒特异性HAI、T细胞和分泌型IgA(sIgA)反应。与在幼儿中观察到的反应不同,LAIV在成人中仅诱导血清HAI反应出现极小的增加,显著低于IIV诱导的反应。LAIV和IIV在成人中均同样仅诱导对具有复制能力的全病毒的短暂T细胞反应。相比之下,LAIV诱导的流感病毒特异性sIgA反应比IIV更强。我们之前的研究表明,由于疫苗诱导的T细胞和/或sIgA反应增加,LAIV在未接触过流感病毒或流感疫苗的幼儿中可能比IIV更具保护作用。我们目前的研究表明,在具有广泛且部分交叉反应的预先存在的流感免疫力的成人中,LAIV增强对循环流感病毒株表达的血凝素(HA)和非HA抗原靶点的sIgA反应可能是疫苗诱导免疫的一个重要附加机制。