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Efficacy of intranasal administration of a truncated NS1 modified live influenza virus vaccine in swine

机译:经鼻内施用NS1修饰的流感病毒活疫苗在猪中的功效

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In the U.S., despite available swine influenza virus (SIV) vaccines, multiple influenza subtypes as well as antigenic and genetic variants within subtypes continue to circulate in the swine population. One of the challenges to control and eliminate SIV is that the currently used inactivated influenza virus vaccines do not provide adequate cross-protection against multiple antigenic variants of SIV in the field. We previously generated a recombinant H3N2 swine influenza virus (SIV) based on the influenza A/SW/TX/4199-2/98 virus (TX98) containing an NS1 gene expressing a truncated NS1 protein of 126 amino acids, TX98-NS1Delta126 virus. This recombinant strain was demonstrated to be highly attenuated in swine and showed potential for use as a modified live-virus vaccine (MLV) after intratracheal application in pigs. However, this route of inoculation is not practical for vaccination in the field. In the present study, we first compared intramuscular and intranasal routes of application of the MLV, and found that the intranasal route was superior in priming the local (mucosal) immune response. Pigs were then vaccinated via the intranasal route and challenged with wild type homologous TX98 H3N2 virus, with a genetic and antigenic variant H3N2 SIV (influenza A/SW/CO/23619/99 virus, CO99) and a heterosubtypic H1N1 SIV (influenza A/SW/IA/00239/2004 virus, IA04). The intranasally vaccinated pigs were completely protected against homologous challenge. In addition, MLV vaccination provided nearly complete protection against the antigenic H3N2 variant CO99 virus. When challenged with the H1N1 IA04 virus, MLV vaccinated animals displayed reduced fever and virus titers despite minimal reduction in lung lesions. In vaccinated pigs, there was no serologic cross-reactivity by HI assays with the heterologous or heterosubtypic viruses. However, there appeared to be substantial cross-reactivity in antibodies at the mucosal level with the CO99 virus in MLV vaccinated pigs.
机译:在美国,尽管有可用的猪流感病毒(SIV)疫苗,但多种流感亚型以及亚型内的抗原和遗传变体仍在猪群中流通。控制和消除SIV的挑战之一是当前使用的灭活流感病毒疫苗无法在现场提供针对SIV的多种抗原变异的足够的交叉保护。我们之前基于流感A / SW / TX / 4199-2 / 98病毒(TX98)生成了重组H3N2猪流感病毒(SIV),其中包含表达126个氨基酸的NS1蛋白质被截断的NS1基因TX98-NS1Delta126病毒。该重组菌株已证明在猪中高度减毒,并在猪气管内应用后显示出用作改良活病毒疫苗(MLV)的潜力。然而,这种接种途径对于现场疫苗接种是不实际的。在本研究中,我们首先比较了MLV的肌肉内和鼻内应用途径,发现鼻内途径在引发局部(粘膜)免疫反应方面具有优势。然后,通过鼻内途径给猪接种疫苗,并用野生型同源TX98 H3N2病毒,遗传和抗原性变体H3N2 SIV(A / SW / CO / 23619/99流感病毒,CO99)和异型H1N1 SIV(A / SW / IA / 00239/2004病毒,IA04)。鼻内接种的猪被完全保护免受同源攻击。另外,MLV疫苗接种提供了针对抗原性H3N2变异CO99病毒的几乎完全保护。当用H1N1 IA04病毒攻击时,接种了MLV的动物显示出降低的发烧和病毒滴度,尽管肺部病变的减少最小。在接种疫苗的猪中,通过HI测定与异源或异型病毒没有血清学交叉反应。但是,MLV疫苗接种的猪在粘膜水平的抗体中与CO99病毒之间存在明显的交叉反应。

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