Garg R, Latimer L, Gerdts V, Potter A, van Drunen Littel-van den Hurk S
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.
Vaccine. 2015 Mar 10;33(11):1338-44. doi: 10.1016/j.vaccine.2015.01.041. Epub 2015 Jan 28.
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.
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。