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首页> 外文期刊>Vaccine >Co-administration of certain DNA vaccine combinations expressing different H5N1 influenza virus antigens can be beneficial or detrimental to immune protection.
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Co-administration of certain DNA vaccine combinations expressing different H5N1 influenza virus antigens can be beneficial or detrimental to immune protection.

机译：表达不同的H5N1流感病毒抗原的某些DNA疫苗组合的共同给药可能有益或有害于免疫保护。

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摘要

Achieving broad-spectrum immunity against emerging zoonotic viruses such as avian influenza H5N1 and other possible pandemic viruses will require generation of cross-protective immune responses. Strong antibody responses generated against the H5HA protein are protective, however, antigenic variation between diverging isolates can interfere with virus neutralization. The current study investigates co-administration of an H5 HA DNA vaccine with other variable and conserved influenza antigens (NA, NP, and M2). All antigens were derived from the A/Hanoi/30408/2005 (H5N1) virus and the contribution towards overall protection and immune activation was assessed against lethal homologous and heterologous challenges. An (HA+NA) combination afforded the best protection against homologous challenge and (HA+NP) was comparable to HA alone against heterologous A/Hong Kong/483/1997 challenge. Interestingly, combining all four H5 antigens at a single site did not improve protection against matched challenge and unexpectedly reduced survival by 30% against a heterologous challenge. Survival was also significantly decreased against heterologous challenge following combination of (HA+NP) with an unrelated antigen. Although there were no significant changes in antibody titres, significantly lower T-cell responses were detected against all antigens except HA in each combination. Co-administration of the vaccines at different injection sites restored T-cell responses but did not improve overall protection. Similar observations were also recorded following combination of HA and NP antigens using two different adenovirus-based backbones. Overall, the data suggest that co-administering certain H5N1 antigens offer better or comparable protection to HA alone, however, combining extra antigens may be unnecessary and lead to unfavourable immune responses
机译：要获得针对新兴的人畜共患病病毒（如H5N1禽流感）和其他可能的大流行性病毒的广谱免疫力，将需要产生交叉保护性免疫应答。针对H5HA蛋白产生的强烈抗体反应具有保护性，但是，不同分离株之间的抗原变异会干扰病毒中和。目前的研究调查了H5 HA DNA疫苗与其他可变且保守的流感抗原（NA，NP和M2）的共同给药。所有抗原均源自A / Hanoi / 30408/2005（H5N1）病毒，并针对致命的同源和异源攻击评估了对总体保护和免疫激活的贡献。 （HA + NA）组合可提供最好的抗同源攻击保护，（HA + NP）与单独的HA相比可抵抗异源A / Hong Kong / 483/1997攻击。有趣的是，在单个位点结合所有四种H5抗原并不能提高针对匹配攻击的保护，并且意外地将针对异源攻击的存活率降低了30％。 （HA + NP）与无关抗原结合后，针对异源攻击的存活率也明显降低。尽管抗体滴度没有显着变化，但在每种组合中，针对除HA以外的所有抗原均检测到明显较低的T细胞应答。在不同注射部位共同施用疫苗可恢复T细胞反应，但不能改善总体保护。使用两种不同的基于腺病毒的主链结合HA和NP抗原后，也记录了类似的观察结果。总体而言，数据表明共同施用某些H5N1抗原可提供优于单独HA的更好或相当的保护，但是，合并额外的抗原可能是不必要的，并且会导致不利的免疫反应

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