Preclinical assessment of safety of maternal vaccination against respiratory syncytial virus (RSV) in cotton rats.
Preclinical assessment of safety of maternal vaccination against respiratory syncytial virus (RSV) in cotton rats.
复制标题
棉花大鼠中母体疫苗接种对呼吸道合胞病毒（RSV）的安全性评估。
DOI：
10.1016/j.vaccine.2017.06.009
复制
发表时间：
2017-07-13
期刊：
影响因子：
5.5
通讯作者：
Boukhvalova MS
中科院分区：
文献类型：
--
作者：
Blanco JCG;Pletneva LM;Otoa RO;Patel MC;Vogel SN;Boukhvalova MS
针对控制新生儿和婴儿RSV感染的母体免疫是目前正在开发的一种有吸引力的疫苗接种策略。在这项工作中，我们模拟了棉鼠（CR）的RSV母体疫苗接种，以回答关于母体疫苗安全性的两个基本问题。我们测试了（i）已知的不安全RSV疫苗（即，FI-RSV批次100疫苗）在存在被动转移的RSV母体免疫的情况下诱导疫苗增强的疾病，以及（ii）当用于对其RSV致敏的母体进行免疫时，相同的FI-RSV疫苗是否可以在CR窝仔中诱导疫苗增强的疾病。我们的数据表明，FI-RSV免疫的幼崽与随后的RSV感染导致疫苗增强的疾病，无论幼崽出生的RSV血清阳性或RSV血清阴性的母亲，和FI-RSV免疫的RSV血清阳性的母亲不存在健康风险的母亲或婴儿。我们的研究还提出了一个关于婴儿免疫接种的新问题，即“安全的”RSV疫苗（例如，肌内施用活RSV）可在血清阳性母亲所生的RSV感染的幼崽中诱导疫苗增强的疾病。最后，我们首次描述了免疫血清阳性CR在分娩时RSV中和抗体滴度的急剧下降。这种下降可能反映了母体免疫抑制，可能准确地指出了RSV感染的脆弱性增加的窗口，可以通过对孕妇进行有效的免疫接种来缓解。
Maternal immunization directed to control RSV infection in newborns and infants is an appealing vaccination strategy currently under development. In this work we have modeled maternal vaccination against RSV in cotton rats (CR) to answer two fundamental questions on maternal vaccine safety. We tested (i), whether a known, unsafe RSV vaccine (i.e., FI-RSV Lot 100 vaccine) induces vaccine enhanced disease in the presence of passively transferred, RSV maternal immunity, and (ii) whether the same FI-RSV vaccine could induce vaccine enhanced disease in CR litters when used to immunize to their RSV-primed mothers. Our data show that FI-RSV immunization of pups with subsequent RSV infection results in vaccine-enhanced disease independent of whether the pups were born to RSV-seropositive or RSV-seronegative mothers, and that FI-RSV immunization of RSV-seropositive mothers does not present a health risk to either the mother or the infant. Our study also raises a novel concern regarding infant immunization, namely that “safe” RSV vaccines (e.g., live RSV administered intramuscularly) may induce vaccine-enhanced disease in RSV-infected pups born to seropositive mothers. Finally, we describe for the first time a sharp decrease in RSV neutralizing antibody titers in immunized seropositive CR at the time of delivery. This decline may reflect maternal immune suppression, potentially pinpointing a window of increased vulnerability to RSV infection that could be alleviated by effective immunization of expectant mothers.
登录
查看更多内容
影响因子：
5.5
作者：
Glenn, Gregory M.;Fries, Louis F.;Flyer, David
通讯作者：
Flyer, David
影响因子：
3.7
作者：
Chu, Helen Y.;Katz, Joanne;Englund, Janet A.
通讯作者：
Englund, Janet A.
DOI：
10.1056/nejmoa0804877
发表时间：
2009-02-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hall CB;Weinberg GA;Iwane MK;Blumkin AK;Edwards KM;Staat MA;Auinger P;Griffin MR;Poehling KA;Erdman D;Grijalva CG;Zhu Y;Szilagyi P
通讯作者：
Szilagyi P
影响因子：
5.5
作者：
Boukhvalova, Marina S.;Prince, Gregory A.;Blanco, Jorge C. G.
通讯作者：
Blanco, Jorge C. G.
影响因子：
5.1
作者：
GLEZEN, WP;PAREDES, A;FRANK, AL
通讯作者：
FRANK, AL