Swedish University of Agricultural Sciences, Host Pathogen Interaction Group, Department of Clinical Sciences, Uppsala, Sweden.
INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France.
PLoS One. 2014 Jun 19;9(6):e100392. doi: 10.1371/journal.pone.0100392. eCollection 2014.
The development of safe and effective vaccines against both bovine and human respiratory syncytial viruses (BRSV, HRSV) to be used in the presence of RSV-specific maternally-derived antibodies (MDA) remains a high priority in human and veterinary medicine. Herein, we present safety and efficacy results from a virulent BRSV challenge of calves with MDA, which were immunized with one of three vaccine candidates that allow serological differentiation of infected from vaccinated animals (DIVA): an SH gene-deleted recombinant BRSV (ΔSHrBRSV), and two subunit (SU) formulations based on HRSV-P, -M2-1, and -N recombinant proteins displaying BRSV-F and -G epitopes, adjuvanted by either oil emulsion (Montanide ISA71VG, SUMont) or immunostimulating complex matrices (AbISCO-300, SUAbis). Whereas all control animals developed severe respiratory disease and shed high levels of virus following BRSV challenge, ΔSHrBRSV-immunized calves demonstrated almost complete clinical and virological protection five weeks after a single intranasal vaccination. Although mucosal vaccination with ΔSHrBRSV failed to induce a detectable immunological response, there was a rapid and strong anamnestic mucosal BRSV-specific IgA, virus neutralizing antibody and local T cell response following challenge with virulent BRSV. Calves immunized twice intramuscularly, three weeks apart with SUMont were also well protected two weeks after boost. The protection was not as pronounced as that in ΔSHrBRSV-immunized animals, but superior to those immunized twice subcutaneously three weeks apart with SUAbis. Antibody responses induced by the subunit vaccines were non-neutralizing and not directed against BRSV F or G proteins. When formulated as SUMont but not as SUAbis, the HRSV N, P and M2-1 proteins induced strong systemic cross-protective cell-mediated immune responses detectable already after priming. ΔSHrBRSV and SUMont are two promising DIVA-compatible vaccines, apparently inducing protection by different immune responses that were influenced by vaccine-composition, immunization route and regimen.
针对牛和人呼吸道合胞病毒（BRSV、HRSV）的安全有效疫苗的开发，以应对存在 RSV 特异性母体来源抗体（MDA）的情况，在人类和兽医医学中仍然是一个高度优先事项。在此，我们介绍了在具有 MDA 的小牛中进行强毒 BRSV 攻毒的安全性和有效性结果，这些小牛接种了三种疫苗候选物之一，这三种疫苗候选物允许对感染和接种动物进行血清学区分（DIVA）：一种 SH 基因缺失的重组 BRSV（ΔSHrBRSV），以及两种基于 HRSV-P、-M2-1 和 -N 重组蛋白的亚单位（SU）制剂，显示 BRSV-F 和 -G 表位，佐剂为油乳剂（Montanide ISA71VG，SUMont）或免疫刺激复合物基质（AbISCO-300，SUAbis）。虽然所有对照动物在 BRSV 攻毒后均出现严重的呼吸道疾病并大量排出病毒，但单次鼻腔接种后五周，ΔSHrBRSV 免疫的小牛几乎完全具有临床和病毒学保护作用。尽管黏膜接种 ΔSHrBRSV 未能诱导可检测的免疫反应，但在强毒 BRSV 攻毒后，迅速产生强烈的记忆性黏膜 BRSV 特异性 IgA、病毒中和抗体和局部 T 细胞反应。每隔三周肌内接种两次 SUMont 的小牛在加强后两周也得到很好的保护。保护效果不如 ΔSHrBRSV 免疫的动物明显，但优于每隔三周皮下接种两次 SUAbis 的小牛。亚单位疫苗诱导的抗体反应是非中和性的，不针对 BRSV F 或 G 蛋白。当与 SUMont 配制时，但与 SUAbis 不同时，HRSV N、P 和 M2-1 蛋白可诱导强烈的全身性交叉保护细胞介导的免疫反应，在首次接种后即可检测到。ΔSHrBRSV 和 SUMont 是两种有前途的 DIVA 兼容疫苗，显然通过不同的免疫反应诱导保护，而这些免疫反应受到疫苗组成、免疫途径和方案的影响。
