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基于 H5 的 DNA 构建体源自选定的高致病性 H5N1 禽流感病毒,可诱导麝香鸭针对低致病性病毒产生高水平的体液抗体。

H5-based DNA constructs derived from selected highly pathogenic H5N1 avian influenza virus induce high levels of humoral antibodies in Muscovy ducks against low pathogenic viruses.

机构信息

Anses (French Agency for Food, Environmental and Occupational Health & Safety), Ploufragan/Plouzané laboratory, Avian and Rabbit Virology Immunology and Parasitology Unit, B,P, 53, Ploufragan 22440, France.

出版信息

Virol J. 2014 Apr 24;11:74. doi: 10.1186/1743-422X-11-74.

Abstract

BACKGROUND

H5 low pathogenic avian influenza virus (LPAIV) infection in domestic ducks is a major problem in duck producing countries. Their silent circulation is an ongoing source of potential highly pathogenic or zoonotic emerging strains. To prevent such events, vaccination of domestic ducks might be attempted but remains challenging. Currently licensed vector vaccines derived from H5N1 HPAIV possess clade 0, clade 2.2 or clade 2.3.4 HA sequences: selection of the best HA candidate inducing the largest cross protection is a key issue. For this purpose, DNA immunization of specific pathogen free Muscovy ducks was performed using different synthetic codon optimized (opt) or native HA genes from H5N2 LPAIV and several H5N1 HPAIV clade 2.1, 2.2.1 and 2.3.4. Humoral cross-immunity was assessed 3 weeks after boost by hemagglutination inhibition (HI) and virus neutralization (VN) against three French H5 LPAIV antigens.

FINDINGS

Vaccination with LP H5N2 HA induced the highest VN antibody titre against the homologous antigen; however, the corresponding HI titre was lower and comparable to HI titres obtained after immunization with opt HA derived from clades 2.3.4 or 2.1. Compared to the other HPAIV-derived constructs, vaccination with clade 2.3.4 opt HA consistently induced the highest antibody titres in HI and VN, when tested against all three H5 LPAIV antigens and H5N2 LPAIV, respectively: differences in titres against this last strain were statistically significant.

CONCLUSION

The present study provides a standardized method to assess cross-immunity based on HA immunogenicity alone, and suggests that clade 2.3.4-derived recombinant vaccines might be the optimal candidates for further challenge testing to vaccinate domestic Muscovy ducks against H5 LPAIV.

摘要

背景

H5 低致病性禽流感病毒(LPAIV)在家禽中的感染是养鸭国家的一个主要问题。它们的隐性传播是潜在高致病性或人畜共患病新兴菌株的持续来源。为了防止此类事件,可能会尝试对家鸭进行疫苗接种,但这仍然具有挑战性。目前,从 H5N1 高致病性禽流感病毒获得许可的载体疫苗具有 0 谱系、2.2 谱系或 2.3.4 谱系的 HA 序列:选择诱导最大交叉保护作用的最佳 HA 候选物是一个关键问题。为此,使用不同的合成密码子优化(opt)或来自 H5N2 LPAIV 和几种 H5N1 HPAIV 2.1、2.2.1 和 2.3.4 谱系的天然 HA 基因,对无特定病原体的麝香鸭进行了 DNA 免疫接种。在加强免疫后 3 周,通过血凝抑制(HI)和病毒中和(VN)对三种法国 H5 LPAIV 抗原评估了体液交叉免疫。

结果

用 LP H5N2 HA 接种可诱导针对同源抗原的最高 VN 抗体效价;然而,相应的 HI 效价较低,与免疫接种源自 2.3.4 或 2.1 谱系的 opt HA 获得的 HI 效价相当。与其他 HPAIV 衍生的构建体相比,用 2.3.4 opt HA 接种可在 HI 和 VN 中始终诱导最高的抗体效价,当分别用所有三种 H5 LPAIV 抗原和 H5N2 LPAIV 进行测试时:与最后一种菌株的效价差异具有统计学意义。

结论

本研究提供了一种基于 HA 免疫原性评估交叉免疫的标准化方法,并表明源自 2.3.4 谱系的重组疫苗可能是进一步挑战试验以接种家养麝香鸭预防 H5 LPAIV 的最佳候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dde2/4029828/e876d68c9aeb/1743-422X-11-74-1.jpg

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