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用新型组合佐剂配制的呼吸道合胞病毒融合蛋白可在带有母源抗体的羔羊中诱导平衡的免疫反应。

The respiratory syncytial virus fusion protein formulated with a novel combination adjuvant induces balanced immune responses in lambs with maternal antibodies.

作者信息

Garg R, Latimer L, Gerdts V, Potter A, van Drunen Littel-van den Hurk S

机构信息

VIDO-Intervac, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3.

VIDO-Intervac, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3; Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E3.

出版信息

Vaccine. 2015 Mar 10;33(11):1338-44. doi: 10.1016/j.vaccine.2015.01.041. Epub 2015 Jan 28.

DOI:10.1016/j.vaccine.2015.01.041
PMID:25637860
Abstract

Respiratory syncytial virus (RSV) causes severe respiratory illness in infants. There are no licensed vaccines to prevent RSV infection. The neonate receives short-term protection from maternally derived antibodies, which, however, can also interfere with the active response to vaccination. A RSV vaccine consisting of a truncated version of the fusion protein formulated with polyI:C, innate defense regulator peptide and polyphosphazene (ΔF/TriAdj), was evaluated in two to three week-old lambs. When delivered intrapulmonary, ΔF/TriAdj elicited IgA production in the lung in addition to a robust systemic response similar to that induced by intramuscular immunization. To investigate potential interference by maternal antibodies, pregnant ewes were vaccinated with ΔF/TriAdj. Lambs born to RSV F-immune or non-immune ewes were then given three vaccinations with ΔF/TriAdj at 3 days, 4 weeks and 8 weeks post-birth. Lambs immunized intramuscularly with ΔF/TriAdj vaccine developed high-affinity ΔF-specific serum IgG and virus neutralizing antibodies, and displayed an increase in the frequency of IFN-γ-secreting cells by in vitro restimulated peripheral blood mononuclear cells. Maternal antibodies did not interfere with the development of an immune response to ΔF/TriAdj in the newborn lambs. These results indicate that immunization of neonates with ΔF/TriAdj is effective even in the face of maternal antibodies.

摘要

呼吸道合胞病毒(RSV)可导致婴儿严重的呼吸道疾病。目前尚无获批用于预防RSV感染的疫苗。新生儿可从母体获得的抗体中获得短期保护,然而,这些抗体也可能干扰对疫苗接种的主动反应。一种由截短形式的融合蛋白与聚肌胞苷酸、先天性防御调节肽和聚磷腈(ΔF/TriAdj)配制而成的RSV疫苗,在2至3周龄的羔羊中进行了评估。当通过肺内给药时,ΔF/TriAdj除了引发类似于肌肉注射免疫诱导的强大全身反应外,还能在肺部诱导IgA产生。为了研究母体抗体的潜在干扰作用,对怀孕母羊接种了ΔF/TriAdj。然后,对RSV F免疫或非免疫母羊所生的羔羊在出生后3天、4周和8周时进行三次ΔF/TriAdj疫苗接种。用ΔF/TriAdj疫苗进行肌肉注射免疫的羔羊产生了高亲和力的ΔF特异性血清IgG和病毒中和抗体,并且通过体外再刺激外周血单核细胞显示分泌IFN-γ的细胞频率增加。母体抗体并未干扰新生羔羊对ΔF/TriAdj免疫反应的发展。这些结果表明,即使存在母体抗体,用ΔF/TriAdj对新生儿进行免疫也是有效的。

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