Vaccine safety and efficacy evaluation of a recombinant bovine respiratory syncytial virus (BRSV) with deletion of the SH gene and subunit vaccines based on recombinant human RSV proteins: N-nanorings, P and M2-1, in calves with maternal antibodies.
Vaccine safety and efficacy evaluation of a recombinant bovine respiratory syncytial virus (BRSV) with deletion of the SH gene and subunit vaccines based on recombinant human RSV proteins: N-nanorings, P and M2-1, in calves with maternal antibodies.
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基于重组人RSV蛋白的疫苗安全性和功效评估，具有SH基因和亚基疫苗的缺失，基于重组人RSV蛋白：N纳米，P和M2-1在具有母体抗体的小腿中，n纳米，P和M2-1。
DOI：
10.1371/journal.pone.0100392
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Valarcher JF
中科院分区：
文献类型：
--
作者：
Blodörn K;Hägglund S;Fix J;Dubuquoy C;Makabi-Panzu B;Thom M;Karlsson P;Roque JL;Karlstam E;Pringle J;Eléouët JF;Riffault S;Taylor G;Valarcher JF
在存在RSV特异性母源抗体（MDA）的情况下，开发针对牛和人呼吸道合胞病毒（BRSV，HRSV）的安全有效疫苗仍然是人类和兽医学的高度优先事项。在本文中，我们提供了用MDA对小牛进行BRSV强毒攻毒的安全性和有效性结果，这些小牛用三种候选疫苗之一免疫，这些候选疫苗允许从血清学上区分感染动物和免疫动物（DIVA）：SH基因缺失的重组牛呼吸道合胞病毒（ΔSHrBRSV）和基于展示BRSV-F和-G表位的HRSV-P、-M2-1和-N重组蛋白的两个亚单位（SU）制剂，通过油乳剂（Montanide ISA 71 VG，SUMont）或免疫刺激复合物基质（AbISCO-300，SUAbis）佐剂化。尽管所有对照动物在BRSV攻毒后均发生重度呼吸道疾病并排出高水平病毒，但Δ SHrBRSV免疫小牛在单次鼻内接种后5周表现出几乎完全的临床和病毒学保护。尽管ΔSHrBRSV粘膜接种未能诱导可检测的免疫应答，但在用强毒BRSV攻毒后，存在快速和强烈的回忆性粘膜BRSV特异性伊加、病毒中和抗体和局部T细胞应答。用SUMont肌内免疫两次（间隔三周）的小牛在加强免疫后两周也得到了良好的保护。保护作用不如Δ SHrBRSV免疫动物明显，但上级优于间隔3周皮下接种SUAbis两次的动物。亚单位疫苗诱导的抗体应答是非中和性的，不针对BRSV F或G蛋白。当配制成SUMont而不是SUAbis时，HRSV N、P和M2-1蛋白诱导强的全身性交叉保护性细胞介导的免疫应答，在引发后即可检测到。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作用，这些免疫反应受到疫苗组成、免疫途径和方案的影响。
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.
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影响因子：
5.5
作者：
Hägglund S;Hu K;Vargmar K;Poré L;Olofson AS;Blodörn K;Anderson J;Ahooghalandari P;Pringle J;Taylor G;Valarcher JF
通讯作者：
Valarcher JF
影响因子：
6.4
作者：
Gaddum, RM;Cook, RS;Taylor, G
通讯作者：
Taylor, G
影响因子：
1.8
作者：
KIMMAN, TG;WESTENBRINK, F;STRAVER, PJ
通讯作者：
STRAVER, PJ
影响因子：
3.8
作者：
KENNEDY, HE;JONES, BV;STOTT, EJ
通讯作者：
STOTT, EJ
影响因子：
3.7
作者：
Furze, JM;Roberts, SR;Taylor, G
通讯作者：
Taylor, G