优化高致病性禽流感疫苗:评估鸡对病毒样颗粒疫苗的抗体反应和保护作用

IF 2.7 Q3 IMMUNOLOGY Vaccine: X Pub Date : 2024-09-06 DOI:10.1016/j.jvacx.2024.100552
Chia-Chi Ku , Cheng-Yu Lin , Chin-Rur Yang , Yu-Chih Yang , Po-Ling Chen , Yi-Te Lin , Pei-Ru Wang , Min-Shi Lee , Shu-Mei Liang , Pei-Wen Hsiao
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引用次数: 0

摘要

背景2020年以来,2.3.4.4b支系高致病性禽流感(H5N1)病毒在以前受影响较小的地区爆发,引起了全球关注。在家禽中实施大规模免疫接种或环状免疫接种应是遏制疾病爆发的一项随时可采取的对策。本研究的重点是开发一种基于病毒样颗粒(VLPs)的重组 H5N2 疫苗,该疫苗针对 2.3.4.4c 支系,该支系是台湾地区自出现高致病性禽流感以来的主要亚支系,导致了 2015 年的大规模疫情爆发。我们使用蒙泰尼71VG佐剂灭活的RG6制定免疫方案,然后进行H5N2-VLP的原加强免疫。我们对佐剂进行了比较:71VG、含 VP3 的 71VG 和含 VP3 的明矾。通过血凝抑制(HI)试验检测血清样本中针对同源疫苗抗原和交叉群抗原的抗体。结果与未添加佐剂的灭活病毒相比,家禽佐剂 71VG 能显著增强鸡对灭活 RG6 病毒的抗体反应。虽然增加抗原剂量可提高 71VG 佐剂 RG6 诱导的抗体滴度,但疫苗对当地流行的高致病性禽流感 H5N2 的交叉反应极小。相反,含有 2.3.4.4c 支系 HA 蛋白的 H5N2-VLP 在 71VG 中添加(FMDV)VP3 佐剂后,可显著促进 HI 抗体反应。所有免疫过 H5N2-VLP 的鸡在当地 2.3.4.4c H5 支系毒株的致命挑战中都存活了下来。我们的研究结果为优化 VLP 疫苗提供了启示,可将目前流行的 H5 病毒的 HA 纳入 VLP 疫苗中,从而有效减轻快速演变的 2.3.4.4 支系 H5 病毒爆发的影响。
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Vaccine optimization for highly pathogenic avian influenza: Assessment of antibody responses and protection for virus-like particle vaccines in chickens

Background

Recent outbreaks of clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 viruses in regions previously less affected since 2020 have raised global concerns. Implementing mass immunization or ring vaccination in poultry should be a countermeasure ready to contain disease outbreaks. This study focuses on developing a recombinant H5N2 vaccine based on virus-like particles (VLPs) against clade 2.3.4.4c, the predominant HPAI subclade in Taiwan since its emergence, leading to a large outbreak in 2015.

Methods

The study aimed to confirm the effectiveness of clade 2.3.4.4c H5N2 VLPs in protecting chickens and identify the best adjuvants for the VLP vaccine. We used Montanide 71VG-adjuvanted inactivated RG6 to establish the immunization protocol, followed by prime-boost H5N2-VLP immunizations. We compared adjuvants: 71VG, 71VG with VP3, and Alum with VP3. Serum samples were tested for antibodies against homologous vaccine antigens and cross-clade antigens by hemagglutination inhibition (HI) assays. Finally, we evaluated the protective efficacy by lethally challenging immunized chickens with H5 viruses from clade 1 or 2.3.4.4c.

Results

Poultry adjuvant 71VG significantly enhanced antibody responses in chickens with inactivated RG6 compared to unadjuvanted inactivated virus. While increasing antigen dosage enhanced 71VG adjuvanted RG6-induced antibody titers, the vaccine displayed minimal cross-reactivity against locally circulating HPAI H5N2. In contrast, H5N2-VLP containing the HA protein of clade 2.3.4.4c, adjuvanted with (FMDV) VP3 in 71VG, significantly promoted HI antibody responses. All H5N2-VLP immunized chickens survived lethal challenges with the local clade 2.3.4.4c H5 strain.

Conclusion

The study demonstrated the immunogenic potential of the VLP vaccine in chickens. Our findings offer insights for optimizing VLP vaccines, allowing the incorporation of the HA of currently circulating H5 viruses to effectively mitigate the impact of the rapidly evolving clade 2.3.4.4 H5 outbreaks.

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来源期刊
Vaccine: X
Vaccine: X Multiple-
CiteScore
2.80
自引率
2.60%
发文量
102
审稿时长
13 weeks
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