A whole virus pandemic influenza H1N1 vaccine is highly immunogenic and protective in active immunization and passive protection mouse models.
A whole virus pandemic influenza H1N1 vaccine is highly immunogenic and protective in active immunization and passive protection mouse models.
复制标题
DOI：
10.1371/journal.pone.0009349
复制
发表时间：
2010-02-23
期刊：
影响因子：
3.7
通讯作者：
Barrett PN
中科院分区：
文献类型：
--
作者：
Kistner O;Crowe BA;Wodal W;Kerschbaum A;Savidis-Dacho H;Sabarth N;Falkner FG;Mayerhofer I;Mundt W;Reiter M;Grillberger L;Tauer C;Graninger M;Sachslehner A;Schwendinger M;Brühl P;Kreil TR;Ehrlich HJ;Barrett PN
最近一种新型猪源性H1N1流感病毒的出现和迅速传播导致了本世纪第一次流感大流行。在开始大规模免疫运动之前，单价疫苗经历了临床前和临床开发。我们在小鼠主动免疫后进行了一系列免疫原性和保护研究，结果表明，全病毒无佐剂疫苗在低剂量下具有免疫原性，并能抵抗活病毒的攻击。该模型的免疫原性与全病毒H5N1疫苗相当，后者在临床研究中已被证明可诱导高水平的血清保护。H1N1大流行性流感疫苗在抵御活病毒攻击方面的效力也被认为与H5N1疫苗相当。使用严重联合免疫缺陷（SCID）小鼠模型也证实了H1N1疫苗的保护功效。结果表明，主动接种H1N1疫苗后获得的小鼠和豚鼠免疫血清在被动转移免疫血清和致死攻击后对SCID小鼠产生100%的保护作用。本研究还比较了对全病毒大流行H1N1和分裂季节性H1N1疫苗的免疫反应。结果表明，全病毒疫苗在小鼠体内诱导了平衡的Th-1和Th-2应答，而分裂疫苗主要诱导Th-2应答，仅诱导极少量的Th-1应答。这些数据支持开始使用相同低剂量的全病毒疫苗进行临床研究，这些全病毒疫苗在以前的全病毒H5N1疫苗临床研究中已被证明具有免疫原性。
The recent emergence and rapid spread of a novel swine-derived H1N1 influenza virus has resulted in the first influenza pandemic of this century. Monovalent vaccines have undergone preclinical and clinical development prior to initiation of mass immunization campaigns. We have carried out a series of immunogenicity and protection studies following active immunization of mice, which indicate that a whole virus, nonadjuvanted vaccine is immunogenic at low doses and protects against live virus challenge. The immunogenicity in this model was comparable to that of a whole virus H5N1 vaccine, which had previously been demonstrated to induce high levels of seroprotection in clinical studies. The efficacy of the H1N1 pandemic vaccine in protecting against live virus challenge was also seen to be equivalent to that of the H5N1 vaccine. The protective efficacy of the H1N1 vaccine was also confirmed using a severe combined immunodeficient (SCID) mouse model. It was demonstrated that mouse and guinea pig immune sera elicited following active H1N1 vaccination resulted in 100% protection of SCID mice following passive transfer of immune sera and lethal challenge. The immune responses to a whole virus pandemic H1N1 and a split seasonal H1N1 vaccine were also compared in this study. It was demonstrated that the whole virus vaccine induced a balanced Th-1 and Th-2 response in mice, whereas the split vaccine induced mainly a Th-2 response and only minimal levels of Th-1 responses. These data supported the initiation of clinical studies with the same low doses of whole virus vaccine that had previously been demonstrated to be immunogenic in clinical studies with a whole virus H5N1 vaccine.
登录
查看更多内容
影响因子：
120.7
作者：
Nolan, Terry;McVernon, Jodie;Greenberg, Michael
通讯作者：
Greenberg, Michael
影响因子：
168.9
作者：
Plennevaux, Eric;Sheldon, Eric;Denis, Martine
通讯作者：
Denis, Martine
影响因子：
158.5
作者：
Ehrlich, Hartmut J.;Mueller, Markus;Barrett, P. Noel
通讯作者：
Barrett, P. Noel
影响因子：
158.5
作者：
Treanor, JJ;Campbell, JD;Wolff, M
通讯作者：
Wolff, M
影响因子：
5.4
作者：
Gupta, M;Mahanty, S;Rollin, PE
通讯作者：
Rollin, PE