Garulli B, Di Mario G, Stillitano M G, Compagnoni D, Titti F, Cafaro A, Ensoli B, Kawaoka Y, Castrucci M R
Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy ; Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, 00185 Rome, Italy.
Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy.
Biomed Res Int. 2014;2014:904038. doi: 10.1155/2014/904038. Epub 2014 May 14.
Recombinant influenza viruses hold promise as vectors for vaccines to prevent transmission of mucosal pathogens. In this study, we generated a recombinant WSN/TatΔ(51-59) virus in which Tat protein lacking residues 51 to 59 of the basic domain was inserted into the N-terminus of the hemagglutinin (HA) of A/WSN/33 virus. The TatΔ(51-59) insertion into the viral HA caused a 2-log reduction in viral titers in cell culture, compared with the parental A/WSN/33 virus, and severely affected virus replication in vivo. Nevertheless, Tat-specific antibodies and T cell responses were elicited upon a single intranasal immunization of BALB/c mice with WSN/TatΔ(51-59) virus. Moreover, Tat-specific immune responses were also detected following vaccine administration via the vaginal route. These data provide further evidence that moderately large HIV antigens can be delivered by chimeric HA constructs and elicit specific immune responses, thus increasing the options for the potential use of recombinant influenza viruses, and their derivatives, for prophylactic and therapeutic vaccines.
重组流感病毒有望作为预防黏膜病原体传播的疫苗载体。在本研究中,我们构建了一种重组WSN/TatΔ(51 - 59)病毒,其中缺失碱性结构域第51至59位残基的Tat蛋白被插入到A/WSN/33病毒血凝素(HA)的N端。与亲本A/WSN/33病毒相比,将TatΔ(51 - 59)插入病毒HA导致细胞培养中的病毒滴度降低了2个对数,并严重影响了病毒在体内的复制。然而,用WSN/TatΔ(51 - 59)病毒对BALB/c小鼠进行单次鼻内免疫后,可引发Tat特异性抗体和T细胞反应。此外,通过阴道途径接种疫苗后也检测到了Tat特异性免疫反应。这些数据进一步证明,中等大小的HIV抗原可通过嵌合HA构建体递送并引发特异性免疫反应,从而增加了重组流感病毒及其衍生物用于预防性和治疗性疫苗的潜在应用选择。